Terapi kanker payudara stadium 0 (non

http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-treating-stage0
Terapi kanker payudara stadium 0 (noninvasif)
Kanker payudara non-invasif jenis lobular carcinoma in situ (LCIS) dan ductal carcinoma in situ
(DCIS) sangat berbeda.
LCIS: Karena jenis ini bukan kanker yang sebenarnya, tidak ada terapi segera atau aktif yang
disarankan untuk wanita dengan LCIS. Namun karena LCIS mningkatkan resiko perkembangan
kanker invasif di kemudian hari, mengikuti perjalanan penyakit/ follow-up sangatlan penting.
Dalam hal ini mammogram tahunan dan uji klinis payudara perlu dilakukan. Follow-up untuk
kedua payudara perlu dilakukan karena biasanya jika terdapat LCIS pada satu payudara maka
resiko terjadi kanker sama meningkatknya untuk kedua sisi payudara. Walaupun tidak ada bukti
yang cukup untuk menyarankan MRI rutin sebagai tambahan mammogram untuk wanita dengan
LCIS, sebaiknya dianjurkan untuk berkonsultasi dengan klinisi mengenai manfaat dan
keterbatasan MRI tahunan sebagai tindakan skrining.
Wanita dengan LCIS biasanya ingin mempertimbangkan penggunaan tamoksifen atau raloksifen
untuk menurunkan resiko kanker payudara, atau berpartisipasi dalam uji klinis pencegahan
kanker payudara. Atau, mereka ingin mendiskusikan juga mengenai strategi pencegahan yang
dapat dilakukan (mencapai bobot badan optimal atau melakukan olahraga) dengan klinisinya.
Beberapa wanita dengan LCIS memilih untuk mastektomi bilateral sederhana (menghilangkan
kedua sisi payudara tetapi bukan nodus limfe axillaris) untuk mengurangi resiko kanker
payudara, terutama jika mereka mempunyai faktor resiko lain, misalnya riwayat keluarga.
Tergantung pilihan wanita ini, dia mungkin ingin segera melakukan atau menunda rekonstruksi
payudara.
DCIS: Pada kebanyakan kasus, wanita dengan DCIS dapat memilih antara terapi
mempertahankan payudara (lumpectomy, biasanya diikiti dengan terapi radiasi) dan mastektomi
sederhana. Menghilangkan nodus limfe (sering kali biopsi nodus linfe sentinel) tidak diperlkan,
tapi dapat dilakukan jika doktor menganggap DCIS memngandung area kanker invasif. Resiko
bahwa DCIS mengandung area kanker invasif makin besar seiring dengan ukuran tumor dan
derajat inti. Banyak doktor melakukan biopsi nodus limfe sentinel jika dilakukan mastektomi.
Terapi radiasi setelah lumpektomi menurunkan kemungkinan kanker kembali pada payudara
yang sama (baik sebagai DCIsi atau sebagai kanker invasif). Lumpektomi tanpa radiasi bukan
merupakan terapi standard, tetapi merupakan pilihan bagi wanita dengan DCIS derajat rendah
atau area yang kecil yang telah dihilangkan bersama dengan batasan jaringan bebas kanker yang
luas. Namun kebanyakan wanita yang mendapat tindakan lumpektomi untuk DCISnya akan
memerlukan terapi radiasi.
Mastektomi mungkin iperlukan jika area DCIS sangat luas, jika payudara menunjukkan beberapa
area DCIS, atau jika lumpektomi tidak dapat menghilangkan seluruh DCIS secara sempurna
(spesimen lumpektomi dan spesimen pengirisan ulang menunjukkan sel kanker dalam atau di
dekat tepian bedah). Wanita yang mastektomi untuk DCIsnya juga dapat mendapat tindakan
rekonstruksi payudara segera atau kemudian.
1 Jika DCISnya bersifat positif untuk reseptor-estrogen ( estrogen receptor-positive), terapi
tamoksifen selama 5 tahun setelah tindakan bedah dapat menurunkan resiko timbulnya DCIS
atau kanker invasif di payudara sisi lainnya.
Last Revised: 06/11/2012
Terapi kanker payudara invasif, berdasarkan
stadium
Tindakan bedah untuk mempertahankan payudara biasanya cocok untuk kanker invasif stadium
dini jika ukuran kanker relatif kecil, walaupun mastektomi juga merupakan salah satu pilihan
tindakan lain. Jika kanker terlalu besar, diperlukan tindakan mastektomi kecuali jika kemoterapi
neoajuvan sebelum tindakan bedah dapat mengecilkan ukuran tumor sehingga cukup dilakukan
tidakan radiasi yang mempertahankan payudara. Pada kasus manapun , nodus limfe di bawah
lengan/ketiak harus dicek apakah mengandung kanker. Radiasi diperlukan untuk hampir semua
pasien yang mendapat tindakan bedah yang mempertahankan payudara dan pada beberapa pasien
yang mendapat tindakan masetektomi. Terapi sistemik ajuvan setelah tindakan bedah bisanya
disarankan untuk semua kanker yang berukuran lebih besar dari 1 cm, juga kadang-kadang pada
tumor yang lebih kecil.
Stadium I
Kanker ini relatif kecil dan mungkin belum menyebar ke nodus limfe (N0) atau ada penyebaran
sedikit ke nodus limfe sentinel (N1mi).
Terapi lokal: Kanker stadium I dapat diatasi dengan tindakan bedah yang mempertahankan
payudara (lumpectomy, partial mastectomy) atau mastektomi. Nodus limfe juga harus dievaluasi,
dengan biopsi nodud limfe sentinel atau dengan pengambilan (dissection) nodus limfe axilla.
Rekonstrukdi payudara dapat dilakukan saat itu juga bersamaan dengan tindakan bedah atau
beberapa waktu kemudian.
Terapi radiasi biasanya diberikan setelah tindakan bedah yang mempertahankan payudara.
Pasien dapat mempertimbangkan tindakan bedah yang mempertahankan payudar tanpa radiasi
jika semua hal berikut benar:
 Usia lebih dari atau sama dengan 70 tahun.
 Ukuran tumor kurang dari atau sama dengan 2 cm dan telah benar-benar diambil
seluruhnya.
 Tumor mengandung reseptor hormon dan diberi terapi hormon.
 Tidak satupun nodus limfe yang telah diambil mengandung kanker.
Beberapa pasien yang tidak memenuhi kriteria tersebut mungkin dapat mencoba menghindari
radiasi, tetapi studi-studi menunjukkan pasien yang tidak mendapat radiasi memiliki
kemungkinan kankernya kembali muncul.
Terapi ajuvan sistemik: Kebanyakan klinisi akan mendiskusikan pro dan kontra terapi ajuvan
hormonal (tamoksifen, inhobitor aromatase, atau keduanya berurutan) dengan semua pasien yang
kankernya positive reseptor hormon (hormone receptor–positive (estrogen atau progesterone)),
2 seberapapun ukuran tumornya. Manfaat terapi hormonal biasanya lebih mungkin dialami oleh
pasien dengan ukuran tumor lebih besar dari 0,5 cm.
Jika tumor lebih kecil dari 1 cm, kemoterapi ajuvan biasanya tidak diberikan. Beberapa klinisi
mungkin menyarankan kemoterapi jika kanker kurang dari 1 cm disetai beberapa karakteristik
kurang baik (misalnya derajat-tinggi, hormone receptor–negative, HER2-positive, atau skor yang
tinggi pada salah satu panel gen). Khemo ajuvan biasanya disarankan untuk kanker yang
berukuran lebih besar.
Untuk kanker yang HER2-positive, ajuvan trastuzumab (Herceptin) biasanya disarankan juga.
Stadium II
Kanker ini biasanya lebih besar dan/atau menyebar ke sekitar nodus limfe.
Terapi lokal: Tindakan bedah dan radiasi sama seperti pada tumor stadium I, kecuali pada
stadium II, terapi radiasi ke dada dapat dipertimbangkan bahkan setelah mastektomi jika tumor
berukuran besar (lebih dari 5 cm) atau sel kanker ditemukan I nodus limfe.
Terapi ajuvan sistemik: Terapi ajuvan sistemik disarankan untuk pasien dengan kanker stadium
II. Terapi yang diberikan mungkin melibatkan terapi hormon, kemoterapi, trastuzumab, atau
kombinasi pilihan tersebut, dan tergantung pada usia pasien, status reseptor-estrogen, dan status
Her2/neu.
Terapi neoajuvan: Salah satu pilihan bagi pasien yang menginginkan mempertahankan
payudara, tetapi ahli bedah menganggap tumor terlalu besar sehingga outcome kurang baik,
adalah terapi neoajuvan (sebelum tindakan bedah) dengan kemoterapi, terapi hormon, dan/atau
trastuzumab untuk mengecilkan tumor.
Jika terapi neoajuvan berhasil mengecilkan tumor, pasien dapat memilih tindakan bedah yang
mempertahankan payudara (misalnya lumpektomi) diikuti dengan tindakan radiasi. Terapi
ajuvan juga dapat diberikan setelah radiasi.
Jika tumor tidak cukup mengecil, maka diperlukan mastektomi. Terapi ajuvan juga dapat
diberikan setelah tindakan bedah, karena tumor tidak mengecil ketika diberikan neoajuvan.
Terapi radiasi juga dapat diberikan setelah tindakan bedah.
Kemungkinan survival pasien dari kanker payudara tidak dipengaruhi oleh apakah pasien
mendapat kemoterapi sebelum atau setelah tindakan bedah.
Stadium III
Kanker stadium III adalah jika tumor lebih besar dari 5 cm atau berkembang ke dalam jaringan
lain di sekitarnya (kulit di atas payudara atau jaringan otot di bawahnya), atau kanker menyebar
ke nodus limfe di sekitarnya. Terapi lokal untuk beberapa kanker stadium III kuranglebih sama
dengan stadium II. Tumor yang relatif kecil (dan belum berkembang ke jaringan sekitarnya)
dapat dihilangkan dengan tindakn bedah yang mempertahankan payudara (lumpektomi)
diikutitindakan radiasi. Jika tidak demikian, maka dilakukan tindakan mastektomi (baik dengan
atau tanpa rekonstrukdi payudara). Biopsi nodus limfe sentinel dapat menjadi pilhan pasien,
namun kebanyakan memerlukan pemeriksaan nodus limfe axilla. Tindakan bedah biasanya
3 diikuti dengan kemoterapi ajuvan sistemik, dan/atau terapi hormon, dan/atau trastuzumab.
Radiasi setelah mastektomi juga sering disarankan.
Seringkali, kanker stadium III ditangani dengan kemoterapi neoajuvan. Tindakan ini mungkin
akan mengecilkan tumor adekuat sehingga dapat dilakukan lumpektomi atau tindakan bedah
yang mempertahankan payudara. Jika tidak, maka harus dilakukan mastektomi. Biasanya juga
dilakukan pemeriksaan nodus limfe axilla. Rekonstruksi segera mungkin merupakan pilihan bagi
beberapa pasien, namun biasanya ditunda sampai setelah terapi radiasi, yang diberikan juga
bahkan untuk mastektomi. Kemoterapi ajuvan juga dapat diberikan, dan terapi hormonal
ditawarkan pada semua pasien yang kankernya hormone receptor–positive.
Beberapa kanker payudara inflamasi termasuk stadium III. Bisanya diterapi dengan kemoterapi
neoajuvan, kadang-kadang dengan radiasi. Kemudian diikuti dengan mastektomi dan
pemeriksaan nodus limfe. Kemudian diberikan terapi ajuvan dengan kemoterapi (dan
trastuzumab jika kanker HER2+), terap radiasi (jika tidak diberikan sebelum tindakan bedah),
dan terapi hormon (jika kanker hormone receptor positive).
Obat-obat terapi ajuvan untuk kanker stadium I sampai III
Terapi ajuvan dapat disarankan, berdasarkan ukuran tumor, penyebaran ke nodus limfe, dan
parameter prognosis lainnya. Biasanya dapat berupa kemoterapi, trastuzumab (Herceptin),
hormon, atau kombinasi obat-obat tersebut.
Terapi hormon: Terapi hormon kemungkinan tidak efektif untuk pasien dengan tumor
hormone receptor-negative. Terapi hormon seringkali ditawarkan untuk pasien dengan kanker
payudara invasif yang hormone receptor–positive berapapun ukuran tumor maupun nodus limfe
yang terlibat.
Pasien yang belum menopause dan tumornya hormone receptor–positive dapat diteapi dengan
tamoxifen, yang menghambat efek estrogen yang diproduksi ovarium. Beberapa klinisi juga
memberikan analog luteinizing hormone-releasing hormone (LHRH)yang akan menghentikan
ofungsi ovarium sementara.Pilihan (permanen) lain adalah pengambilan ovarium melalui
tindakan bedah (oophorectomy). Namun, belum jelas apakah pengambilan ovarium atau
mengehntikan kerjanya akan membantu kerja tamoksfe. Jika pasien mengalami menopause
dalam 5 tahun sejak menggunakan tamoksifen (baik secara alami maupun karena ovariumnya
diangkat), pasien dapat mengganti tamoksifen dengan obat lain inhibitor aromatase.
Terkadang pasien dapat ,engalami berhentinya menstruasi setealh kemoterapi atau ketika diterapi
tamoksifen. Namun tidak berarti pasien ini mengalami menopause. Klinisi dapat melakukan uji
darah untuk mengetahui keadaan beberapa hormon untuk mengetahui status menopausenya. Hal
ini penting karena obat inhibitor aromatase hanya bermanfaat untuk pasien setelah menopause.
Pasien yang tidak lagi menstruasi, atau yang memang telah menopause berapaun usianya, dan
pasien yang tumornya hormone receptor–positive biasanya akan mendapat terapi ajuvan baik
dengan inhbitor aromatase (biasanya selama 5 tahun), atau dengan tamoksifen selama 2-5 tahun
diikuti dengan inhibitor aromatase selama 3-5 tahun lagi. Pasien yang tidak dapat mengkonsumsi
inhibior aromatase dapat menggunakan tamoksifen sebagai alternatif selama 5 tahun.
Seperti telah disampaikan sebelumnya, masih banyak yang belum bisa dijawab bagaiman cara
menggunakan obat-obat ini yang sebaik-baiknya. Sebagai contoh, masih belum jelas apakah
memberikan terapi ajuvan dengan salah satu obat tersebut lebih baik daripada dengan pemberian
4 tamoksifen elama beberpa waktu kemudian dilanjutkan inhibitor aromatase. Atau berapa lama
waktu penggunaan inhibitor aromatase yang optimal. Banyak studi yang sedang dilakukan untuk
menjawab pertanyaan-pertanyaan demikian.
Jika kemoterapi juga harus diberikan, terapi hormon biasanya diberikan jika kemoterapi telah
sempurna selesai.
Kemoterapi: Keoteapi biasanya disarankan untuk semua pasien dengan kanker payudara invasif
yang bersifat hormone receptor-negative, dan bagi pasien dengan tumor hormone receptorpositive yang mungkin akan mendapat manfaat tambahan dengan pemnggunaan kmoterapi
bersama terapi hormon, berdasarkan stadium dan karakteristik tumornya.
Kemoterapi ajuvan dapat menurunkan resiko kanker kembali/kambuh, tetapi tidak
menghilangkan resiko sama sekali. Sebelum memutuskan apakah pengobatan tepat, penting
untuk megetahu seberapa resiko kanker kambuh dan seberapa jauh terapi ajuvan dapat
mengurangi resiko tersebut.
Regimen kemoterapi dapat dilihat pada daftar, biasanya berkisar antara 4-6 bulan. Pada beberapa
kasus mungkin diperlukan kemoterapi dengan interval dosis yang lebih rapat (dose-dense).
Trastuzumab (Herceptin): Pasien yang kankernya HER2-positive biasanya mendapat
trastuzumab bersama dengan kemoterapi.
Salah satu regimen yag umum adalah doxorubicin (Adriamycin) dan cyclophosphamide selama 3
bulan, diikuti dengan paclitaxel (Taxol) dan trastuzumab. Paclitaxel diberikan selama 3 bulan,
sedangkan trastuzumab diberikan total selama 1 tahun.
Salah satu kekhawatiran klinisi adalah jika trastuzumab diberikan terlalu cepat setealh pemberian
doxorubicin dapat mengakibatkan masalah pada jantung, sehingga fungsi jantung harus
dimonitor dengan ketat selama terapi antara lain dengan echocardiograms atau pencitraan
MUGA.
Untuk mengurangi efek samping pada jantung, klinisi juga mencoba kombinasi terapi yang tidak
mengandung doxorubicin. Salah satu regimen demikian adalah TCH, yaitu docetaxel (Taxotere)
dan carboplatin setiap 3 minggu bersama dengan trastuzumab (Herceptin) selama 6 siklus.
Kemudian diikuti dengan trastuzumab setiap 3 minggu selama 1 tahun.
Uji pola gene (gene pattern test): Beberapa klinisi mungkin menggunakan uji/pemeriksaan
pola gen untuk membantu menentukan apakah perlu terapi ajuvan pada kanker payudara stadium
I dan II. Contoh uji demikian antara lain Oncotype DX dan MammaPrint, yang dijelaskan lebih
detil pada bagian bagaimana kanker payudara didiagnosis "How is breast cancer diagnosed?" Uji
demikian dilakukan menggunakan sampel jaringan kanker payudara. Yang dilihat adalah fungsi
beberapa gen dalam kanker untuk membantu memperkirakan resiko kambuhnya kenker setealh
terapi. Ui ini tidak akan membantu klinisi menetukan terapi hormon atau kemoteapi apa yang
terbaik bagi pasien. Uji ini membantu klinisi mengetahui seberapa manfaat terapi ajuvan bagi
pasien. Studi klinis besar masih dilakukan untuk mengetahui pakah uji gen demikian dapat
membantu klinisi ketika menghadapi pasien dengan tumor kecil dan nodus limfe yang bersih.
Alat bantu online untuk membantu mengambil keputusan: Untuk membantu memilih terapi
ajuvan apa yang tepat untuk pasien, psien dapat mengunjungi situs Mayo Clinic Web di
www.mayoclinic.com dan mengetik "adjuvant therapy for breast cancer" ke kotak pencarian.
5 Lam itu akan membantu psien memahami manfaat yang dapat diharapkan dan apa keterbatasan
terapi ajuvan.
Pedoman online lain, seperti www.adjuvantonline.com, didesain utnuk digunkan oleh
profesional kesehatan. Situs wen tersebut menyediakan infomrasi mengenai resiko kanker akan
kambuh dalam 10 tahun ke depan dan manfaat apa yang dapat diharapkan dari terapi hormon
dan/atau kemoterapi.
Stadium IV
Kanker stadium IV telah menyebar di luar payudara dan nodus limfe ke bagian tubuh lainnya.
Kanker payudara bisanya menyebar ke tulang, hati dan paru-paru. Kanker stadium IV juga dapat
menyebar ke otak, atau organ lain, termasuk mata.
Walaupun tindakan bedah dan/atau radiasi dapat bermanfaat pada situasi tertentu, terapi sistemik
masih merupakan terapi yang utama. Tergantung pada banyak faktor, terapi dapat berupa
hormonal, kemoterapi, terapi yang ditargetkan (targeted therapy) seperti trastuzumab,
pertuzumab (Perjeta), dan lapatinib (Tykerb), atau kombinasi obat-obat tersebut. Terapi dapat
mengecilkan tumor, memperbaiki gejala, dan membantu pasien hidup lebih panjang, namun
tidak dapat mengusir kanker sepenuhnya dan seterusnya.
Trastuzumab dapat membantu psien dengan kanker yang HER2-positive hidup lebih lama jika
diberikan bersama dengan kemoterapi pertama untuk kanker stadiumIV. Pemberian pertuzumab
dengan kemoteapi dan trastuzumab mungkin lebih baik lagi. Pemberian Trastuzumab juga dapat
membantu jika diberikan bersama dengan terapi hormon letrozole. Masih belum jelas berapa
lama terapi trastuzumab atau pertuzumab harus dilanjutkan.
Semua terapi sistemik untuk kanker payudara— terapi hormon, keoterapi dan terapi yang
ditargetkan — mempunyai efek samping.
Terapi radiasi dan/atau tindakan bedah juga dapat diberikan pada situasi berikut:







Ketika tumor payudara mengakibatkan luk terbuka pada payudara (atau dada)
Untuk mengatasi sejumlah kecil metasatases pada area tertentu
Untuk mencegah patah tulang
Ketika are kanker menyebar menekan korda spinalis
Untuk mengatasi blokade pada hati
Untuk meringankan nyeri tau gejala lain
Ketika kanker menyebar ke otak
Terapi lokal demikian harus jelas tujuannya (dijelaskan pada pasien), apakah untuk
menyembuhkan kanker, mencegah atau mengatasi gejala.
Pada beberapa kasus terapi regional (obat diberikan langsung ke area tertentu, misalnya cairan
sekitar otak atau ke dalam hati) dapat juga bermanfaat.
Terapi untuk meringankan gejala tergantung pada daerah penyebaran kanker. Sebagai contoh,
nyeri akibat metastase tulang dapat diatasi dengan terapi radiasi sinar eksternal dan/atau
bifosfonat misalnya pamidronate (Aredia) atau asam zoledronat (zoledronic acid/Zometa).
Kebanyakan klinisi menganjurkan bisphosphonates atau denosumab (Xgeva), bersama dengan
6 calcium dan vitamin D, untuk semua pasien yang kanker payudaranya telah menyebar ke tulang
(lihat juga informasi pada bab Bone Metastasis.)
Kanker stadium lanjut yang terus berkembang selama terapi: Terapi untuk kanker stadium
lanjut dapa mengecilkan atau mempelambat pertumbuhan sel-sel kanker (seringkali untuk
bertahun-tahun), namun diperkirakan obat akan berhenti bkerja setealh beberapawaktu. Terapi
lanjutan pada keadaan ini tergantung pada beberapa faktor, termasuk terapi sebelumnya, lokasi
kanker, usia pasien, kesehatan umum, dan keinginan pasien untuk melanjutkna terapi.
Untuk kanker yang hormone receptor–positive yang diterapi hormon, menggantinya denga terapi
hormon lain mugkin bermanfaat. Jika tidak, maka langkah selanjutnya adalah kemoterapi.
Untuk kanker yang tidak lagi merespon regimen kemoterapi tertentu, dapat diganti dengan
regimen kemoterapi lainnya. Banyak obat dan kombinasi yang dapat digunakan untuk mengatasi
kanker payudara. Namun, setiap kali kanker berlanjut/progresi selama terapi maka terapi
berikutnya akan makin kecil kemungkinan berefek.
Kanker HER2-positive yang tidak lagi merespon trastuzumab mungkin masih bisa merespon
lapatinib. Lapatinib juga menyerang protein HER2. Obat ini bisanya diberikan bersama
kemoterapi capecitabine (Xeloda), namun bisa juga bersama kemoterapi lain, bersama
trastuzumab, atau bahkan tunggal (tanpa kemoterapi).
Karena terapi saat ini kelihatannya tidak menyembuhkan kanker stadium lanjut, pasien dapat
dianjurkan untuk berpartisipasi dalam uji clinical trial. Menggunakan terapi lain yang potensial.
Kanker payudara kambuh (rekurensi)
Kanker disebut kambuh (recurrent) jika muncul kembali setealh terapi. Rekurensi dapat bersifat
lokal (di payudara yang sama atau bekas mastektomi) atau di tempat yang lain. Jarang, kanker
payudara muncul kembali di nodus limfe sekitar). Keadaan ini disebut rekurensi regional.
Kanker yang ditemukan di payudara yang sebelahnya tidak disebut rekurensi—melainkan
termasuk kanker baru yang perlu diterapi tersendiri.
Rekurensi lokal: Terapi kanker rekurensi lokal tergantung pada tindakan terapi sebelumnya.
Jika pasien sebelumnya mendapat tindakan yang mempertahankan payudara, rekurensi lokal
biasanya diatasi dengan mastektomi. Jika terapi sebelumnya adalah mastektomi, rekurensi
didaerah sekitar mastektomi jika memungkinkan diatasi dengan tindakan pengambilan untuk
menghilangkan sel-sel kankerKemudian diikuti dengan terapi radiasi, hanya jika belum pernah
dilakukan setelah tindakan bedah awal. Radiasi tidak bolh diberikan pada daerah yang sama dua
kali. Pada kasus manapun, terapi hormon, trastuzumab, kemoterapi, ataukombinasinya dapat
digunakan setealh tindakan bedah dan/atau radiasi.
Rekurensi regional: Jika kanker kambuh sebagai bentuk penyebaran ke nodus linfe sekitarnya
(misalnya di bawah lengan/ketiak atau pada tulang leher), maka diatasi dengan mengambil nodus
limfe. Kemudaian diikuti dengan radiasi pada are yang bersangkutan. Terapi sistemik
(kemoterapi atau hormon) dapat dipertimbangkan setelah terapi lokal.
Rekurensi distant/jauh: Secara umum, pasien yang mengalami rekurensi pada organ-organ
tulang, paru-paru, otak, dll, diatasi dengan cara seperti pada stadium IV. Perbedaannya hanya
pada respon terapi yang mungkin dipengaruhi oleh terapi sebelumnya yang telah diterima pasien.
Lihat juga informasi pada bab lain (When Your Cancer Comes Back: Cancer Recurrence).
7 Regimen Kemoterapi
Completely revised and updated, The Elsevier Guide to Oncology Drugs and Regimens (2012
edition) provides more than 290 drug regimens commonly used in the treatment of 26 cancer
types. Recommended supportive therapy for the adverse effects most commonly associated with
each regimen is also included.
Results for Breast AC [dose­dense] (doxorubicin [Adriamycin], cyclophosphamide) This Regimen Is Used for:Adjuvant therapy Recurrent or metastatic disease therapy Regimen Details Doxorubicin 60 mg/m2 I.V. on day 1 Cyclophosphamide 600 mg/m2 I.V. on day 1 Repeat cycle every 21 days... AC→T Dose­dense (doxorubicin [Adriamycin], cyclophosphamide→paclitaxel [Taxol]) This Regimen Is Used for:Adjuvant therapy Regimen Details Doxorubicin 60 mg/m2 I.V. on day 1 Cyclophosphamide 600 mg/m2 I.V. on day 1 Repeat cycle every 21 days for four cycles. Followed by Paclitaxel... Bevacizumab, paclitaxel This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Bevacizumab 10 mg/kg I.V. over 90 minutes on days 1 and 15; if tolerated, may decrease rate of infusion to 30 to 60 minutes Paclitaxel... CMF (cyclophosphamide, methotrexate, 5­fluorouracil) This Regimen Is Used for:Adjuvant therapy Metastatic or recurrent disease therapy Regimen Details For patients younger than age 60: Cyclophosphamide 100 mg/m2 P.O. on days 1 through 14 Methotrexate 40... Capecitabine This Regimen Is Used for:Metastatic or recurrent disease therapy Biomarker Testing:DPD Regimen Details Capecitabine 1,250 mg/m2 P.O. twice daily on days 1 through 14 Repeat cycle every 21 days. References: Bajetta... Docetaxel This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Docetaxel 60 to 100 mg/m2 I.V. over 1 hour on day 1 Repeat cycle every 21 days. Or Docetaxel 35 to 40 mg/m2 I.V. over 30... Docetaxel, trastuzumab [Herceptin] This Regimen Is Used for:Metastatic or recurrent disease therapy for HER2‐overexpressing breast cancer Biomarker Testing:HER2 Regimen Details Docetaxel 80 to 100 mg/m2 I.V. on day 1 Repeat cycle every... Doxorubicin This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Doxorubicin 60 to 75 mg/m2 I.V. on day 1 Repeat cycle every 21 days. Or Doxorubicin 20 mg/m2 I.V. on day 1 Repeat cycle... Epirubicin This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Epirubicin 60 to 90 mg/m2 I.V. on day 1 Repeat cycle every 21 days. References: Bastholt L, Dalmark M, Gjedde SB, et al.... 8 Eribulin This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Eribulin 1.4 mg/m2 I.V. on days 1 and 8 Repeat cycle every 21 days. References: Twelves C, Loesch D, Blum JL, et al. A phase... FAC (or CAF) (5­fluorouracil, doxorubicin [Adriamycin], cyclophosphamide) This Regimen Is Used for:Adjuvant therapy Metastatic or recurrent disease therapy Regimen Details 5‐
Fluorouracil (5‐FU) 500 mg/m2 I.V. on day 1 Doxorubicin 50 mg/m2 I.V. on day 1 Cyclophosphamide 500 mg/m2... FEC­100 (5­fluorouracil, epirubicin, cyclophosphamide) This Regimen Is Used for:Adjuvant therapy Metastatic or recurrent disease therapy Regimen Details 5‐
Fluorouracil 500 mg/m2 I.V. on day 1 Epirubicin 100 mg/m2 I.V. on day 1 Cyclophosphamide 500 mg/m2 Repeat... GT (gemcitabine, paclitaxel [Taxol]) This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Paclitaxel 175 mg/m2 I.V. over 3 hours on day 1 only before gemcitabine Gemcitabine 1250 mg/m2 I.V. over 30 minutes on days... Hormone therapy This Regimen Is Used for:Adjuvant and neoadjuvant therapy (tamoxifen, anastrozole, exemestane, letrozole) Metastatic disease therapy (tamoxifen, anastrozole, exemestane, letrozole) Prevention therapy (tamoxifen,... Ixabepilone (with or without capecitabine) This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Ixabepilone 40 mg/m2 I.V. on day 1 With or without Capecitabine 2,000 mg/m2/day (in two divided doses) P.O. on days 1 to... Lapatinib, capecitabine This Regimen Is Used for:Metastatic or advanced HER2‐overexpressing breast cancer Biomarker Testing:HER2 Regimen Details Lapatinib 1250 mg P.O. on days 1 to 21 Capecitabine 2000 mg/m2/day (in two divided... Nanoparticle albumin­bound (nab)­paclitaxel This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Nab‐paclitaxel 260 mg/m2 I.V. on day 1 Repeat cycle every 21 days. Or Nab‐paclitaxel 100 mg/m2 I.V. on day 1 Repeat cycle... Paclitaxel This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Paclitaxel 175 or 250 mg/m2 I.V. over 3 hours on day 1 Repeat cycle every 21 days. Or Paclitaxel 80 mg/m2 I.V. over 1 hour... Paclitaxel, trastuzumab This Regimen Is Used for:Recurrent or metastatic HER2‐overexpressing breast cancer Biomarker Testing:HER2 Regimen Details Paclitaxel 175 mg/m2 I.V. over 3 hours on day 1 Repeat cycle every 21 days. With Trastuzumab... 9 Pegylated liposomal doxorubicin This Regimen Is Used for:Metastatic or recurrent disease therapy Regimen Details Pegylated liposomal doxorubicin 40 to 45 mg/m2 I.V. over 1 hour on day 1 Repeat cycle every 21 to 28 days. References: Al‐
Batran... TAC (docetaxel [Taxotere], doxorubicin [Adriamycin], cyclophosphamide) This Regimen Is Used for:Adjuvant therapy Regimen Details Docetaxel 75 mg/m2 I.V. on day 1 Doxorubicin 50 mg/m2 I.V. on day 1 Cyclophosphamide 500 mg/m2 I.V. on day 1 Repeat cycle every 21 days for six... TC (docetaxel [Taxotere], cyclophosphamide) This Regimen Is Used for:Adjuvant therapy Regimen Details Docetaxel 75 mg/m2 I.V. on day 1 Cyclophosphamide 600 mg/m2 I.V. on day 1 Repeat cycle every 21 days for four cycles. References: Jones SE, Savin... TCH → (Docetaxel [Taxotere]/Carboplatin, Trastuzumab [Herceptin]) This Regimen Is Used for:Adjuvant therapy for HER2‐overexpressing breast cancer Biomarker Testing:HER2 (trastuzumab) Regimen Details Docetaxel 75 mg/m2 I.V. on day 1 Carboplatin AUC 6 I.V. on day 1 Repeat... Trastuzumab, vinorelbine This Regimen Is Used for:Recurrent or metastatic HER2‐overexpressing breast cancer Biomarker Testing:HER2 Regimen Details Trastuzumab 4 mg/kg I.V. over 90 minutes on day 1 Followed by 2 mg/kg I.V. over... [DOSE­DENSE] AC→TH (doxorubicin [Adriamycin], cyclophosphamide→paclitaxel [Taxol], trastuzumab [Herceptin]) This Regimen Is Used for:Adjuvant therapy for HER2‐overexpressing breast cancer Biomarker Testing:HER2 Regimen Details AC→TH (doxorubicin, cyclophosphamide→paclitaxel, trastuzumab) Doxorubicin 60 mg/m2... AC [dose­dense] (doxorubicin [Adriamycin], cyclophosphamide) Adjuvant therapy Recurrent or metastatic disease therapy Regimen Details Doxorubicin 60 mg/m2 I.V. on day 1
Cyclophosphamide 600 mg/m2 I.V. on day 1
Repeat cycle every 21 days for four cycles.
[Dose-Dense] Doxorubicin 60 mg/m2 I.V. on day 1
Cyclophosphamide 600 mg/m2 I.V. on day 1
Repeat cycle every 14 days for four cycles.
References:
10 Burstein HJ, Parker LM, Keshaviah A, et al. Efficacy of pegfilgrastim and darbepoetin alfa as
hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin
Oncol. 2005;23:8340-8347.
Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus
conventionally scheduled and sequential versus concurrent combination chemotherapy as
postoperative adjuvant treatment of node-positive primary breast cancer. First report of
Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21:14311439.
Dang C, Fornier M, Sugarman S, et al. The safety of dose-dense doxorubicin and
cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu
overexpressed/amplified breast cancer. J Clin Oncol. 2008;26:1216-1222.
Fisher B, Anderson S, Wickerham DL, et al. Increased intensification and total dose of
cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary
breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin
Oncol. 1997;15:1858-1869.
Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with
and without interval reinduction therapy compared with six months of cyclophosphamide,
methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifennonresponsive tumors. Results from NASBP B-15. J Clin Oncol. 1990;8:1483-1496.
Nabholtz J, Falkson C, Campos D, et al. Docetaxel and doxorubicin compared with doxorubicin
and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a
randomized, multicenter, phase III trial. J Clin Oncol. 2003;21:968-975.
Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for moderate emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 
epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. 11 


epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. AC→T Dose­dense (doxorubicin [Adriamycin], cyclophosphamide→paclitaxel [Taxol]) Adjuvant therapy Regimen Details Doxorubicin 60 mg/m2 I.V. on day 1
Cyclophosphamide 600 mg/m2 I.V. on day 1
Repeat cycle every 21 days for four cycles.
Followed by
Paclitaxel 175-225 mg/m2 I.V. over 3 hours on day 1
Repeat cycle every 21 days for four cycles.
Or
Paclitaxel 80 mg/m2 I.V. over 1 hour weekly for 12 weeks
[Dose-dense]Doxorubicin 60 mg/m2 I.V. on day 1
Cyclophosphamide 600 mg/m2 I.V. on day 1
Repeat cycle every 14 days for four cycles.
Followed by
Paclitaxel 175 mg/m2 I.V. over 3 hours on day 1
Repeat cycle every 14 days for four cycles.
Comments:
Administer filgrastim with dose-dense regimen.
References:
Burstein HJ, Parker LM, Kashaviah A, et al. Efficacy of pegfilgrastim and darbepoetin alfa as
hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin
Oncol. 2005;23:8340-8347.
Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus
conventionally scheduled and sequential versus concurrent combination chemotherapy as
postoperative adjuvant treatment of node-positive primary breast cancer. First report of
Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21:14311439.
12 Lee KH, Im SA, Oh DY, et al. Prognostic significance of bcl-2 expression in stage III breast
cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as
adjuvant chemotherapy. BMC Cancer. 2007;7:63.
Mamounas EP, Bryant J, Lembersky B, et al. Paclitaxel after doxorubicin plus
cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from
NSABP 13-28. J Clin Oncol. 2005;23:3686-3696.
Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast
cancer. N Engl J Med. 2008;358:1663-1671.
Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized
trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without
trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23:7811-7819.
Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for high risk. On day 1 of paclitaxel regimens, follow acute‐onset regimen for low emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended. For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. 13 For hypersensitivity reactions To prevent hypersensitivity reactions, consider one of the following before the start of chemotherapy administration: 


dexamethasone 8 mg P.O. twice daily for 3 days starting 1 day before chemotherapy, or 20 mg P.O. 12 hours and 6 hours before chemotherapy, or 20 mg I.V. before chemotherapy diphenhydramine 50 mg I.V. 30 to 60 minutes before chemotherapy cimetidine 300 mg I.V. or ranitidine 50 mg I.V. 30 to 60 minutes before chemotherapy Bevacizumab, paclitaxel Metastatic or recurrent disease therapy Regimen Details Bevacizumab 10 mg/kg I.V. over 90 minutes on days 1 and 15; if tolerated, may decrease rate of
infusion to 30 to 60 minutes
Paclitaxel 90 mg/m2 I.V. on days 1, 8, and 15
Repeat cycle every 28 days.
References:
Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for
metastatic breast cancer. N Engl J Med. 2007;357:2666-2676.
Supportive Therapy For nausea and vomiting On days 1and 15, follow acute‐onset antiemetic regimen for minimal emetic risk. On day 8, follow acute‐
onset antiemetic regimen for low emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended as needed. For hypersensitivity reactions To prevent hypersensitivity reactions, consider one of the following before the start of chemotherapy administration: 


dexamethasone 8 mg P.O. twice daily for 3 days starting 1 day before chemotherapy, or 20 mg P.O. 12 hours and 6 hours before chemotherapy, or 20 mg I.V. before chemotherapy diphenhydramine 50 mg I.V. 30 to 60 minutes before chemotherapy cimetidine 300 mg I.V. or ranitidine 50 mg I.V. 30 to 60 minutes before chemotherapy CMF (cyclophosphamide, methotrexate, 5­fluorouracil) Adjuvant therapy Metastatic or recurrent disease therapy Regimen Details For patients younger than age 60:
Cyclophosphamide 100 mg/m2 P.O. on days 1 through 14
Methotrexate 40 mg/m2 I.V. on days 1 and 8
14 5-Fluorouracil (5-FU) 600 mg/m2 I.V. on days 1 and 8
Repeat cycle every 28 days.
For patients older than age 60:
Cyclophosphamide 100 mg/m2 P.O. on days 1 through 14
Methotrexate 30 mg/m2 I.V. on days 1 and 8
5-FU 400 mg/m2 I.V. on days 1 and 8
Repeat cycle every 28 days.
References:
Amadori D, Nanni O, Marangolo M, et al. Disease-free survival advantage of adjuvant
cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly
proliferating breast cancer: a randomized multicenter study. J Clin Oncol. 2000;18:3125-3134.
Amadori D, Nanni O, Volpi A, et al. Phase III randomized multicenter study on the effects of
adjuvant CMF in patients with node-negative, rapidly proliferating breast cancer: twelve-year
results and retrospective subgroup analysis. Breast Cancer Res Treat. 2008;108:259-264.
Bonadonna G, Brusamolino E, Valagussa P, et al. Combination chemotherapy as an adjuvant
treatment in operable breast cancer. N Engl J Med. 1976;294:405-410.
Bonadonna G, Moliterni A, Zambetti M, et al. 30 years' follow up of randomised studies of
adjuvant CMF in operable breast cancer: cohort study. BMJ. 2005;330:217-222.
Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant
cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer—the results of
20 years of follow-up. N Engl J Med. 1995;332:901-906.
Supportive Therapy For nausea and vomiting On days 1 and 8, follow acute‐onset antiemetic regimen for moderate emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended as needed. On days 2 through 7 and 9 through 14, follow acute-onset antiemetic regimen for moderate
emetic risk. Anticipatory, breakthrough, and delayed-onset regimens are recommended as
needed.
For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. 15 *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. Capecitabine Metastatic or recurrent disease therapy Biomarker Testing: DPD Regimen Details Capecitabine 1,250 mg/m2 P.O. twice daily on days 1 through 14
Repeat cycle every 21 days.
References:
Bajetta E, Procopio G, Celio L, et al. Safety and efficacy of two different doses of capecitabine
in the treatment of advanced breast cancer in older women. J Clin Oncol. 2005;23:2155-2161.
Blum JL, Jones SE, Buzdar AU, et al. Multicenter phase II study of capecitabine in paclitaxelrefractory metastatic breast cancer. J Clin Oncol. 1999;17:485-493.
Fumoleau P, Largillier R, Clippe C, et al. Multicentre, phase II study evaluating capecitabine
monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Eur J
Cancer. 2004;40:536-542.
Supportive Therapy For nausea and vomiting On days 1 through 14, follow acute‐onset antiemetic regimen for low emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended as needed. For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 
epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. 16 


epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For diarrhea Follow the National Cancer Institute’s guidelines for grading and treating diarrhea based on severity of symptoms on a scale of 1(mild) to 4 (severe or life‐threatening). Docetaxel Metastatic or recurrent disease therapy Regimen Details Docetaxel 60 to 100 mg/m2 I.V. over 1 hour on day 1
Repeat cycle every 21 days.
Or
Docetaxel 35 to 40 mg/m2 I.V. over 30 minutes on days 1, 8, and 15
Repeat cycle every 28 days.
References:
Harvey V, Mouridsen H, Semiglazov V, et al. Phase III trial comparing three doses of docetaxel
for second-line treatment of advanced breast cancer. J Clin Oncol. 2006;24:4963-4970.
Jones SE, Erban J, Overmoyer B, et al. Randomized phase III study of docetaxel compared with
paclitaxel in metastatic breast cancer. J Clin Oncol. 2005;23:5542-5551.
Nabholtz J-M, Senn HJ, Bezwoda WR, et al. Prospective randomized trial of docetaxel versus
mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous
anthracycline-containing chemotherapy. J Clin Oncol. 1999;17:1413-1424.
17 Rivera E, Mejia JA, Arun BK, et al. Phase 3 study comparing the use of docetaxel on an every-3week versus weekly schedule in the treatment of metastatic breast cancer. Cancer.
2008;112:1455-1461.
Stemmler J, Mair W, Stauch M, et al. High efficacy and low toxicity of weekly docetaxel given
as first-line treatment for metastatic breast cancer. Oncology. 2005;68:71-78.
Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for low emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended. For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For hypersensitivity reactions To prevent hypersensitivity reactions, consider one of the following before the start of chemotherapy administration: 


dexamethasone 8 mg P.O. twice daily for 3 days starting 1 day before chemotherapy, or 20 mg P.O. 12 hours and 6 hours before chemotherapy, or 20 mg I.V. before chemotherapy diphenhydramine 50 mg I.V. 30 to 60 minutes before chemotherapy cimetidine 300 mg I.V. or ranitidine 50 mg I.V. 30 to 60 minutes before chemotherapy Docetaxel, trastuzumab [Herceptin] Metastatic or recurrent disease therapy for HER2‐overexpressing breast cancer 18 Biomarker Testing: HER2 Regimen Details Docetaxel 80 to 100 mg/m2 I.V. on day 1
Repeat cycle every 21 days.
With
Trastuzumab 8 mg/kg I.V. over 90 minutes on day 1 of first cycle
Followed by
6 mg/kg I.V. over 90 minutes every 21 days
Or
Docetaxel 35 mg/m2 I.V. weekly
With
Trastuzumab 4 mg/kg I.V. over 90 minutes on day 1
Followed by
2 mg/kg I.V. over 30 minutes weekly
References:
Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of
humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing
metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin
Oncol. 1999;17:2639-2648.
Esteva FJ, Valero V, Booser D, et al. Phase II study of weekly docetaxel and trastuzumab for
patients with HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:1800-1808.
Forbes JF, Kennedy J, Pienkowski T, et al. BCIRG 007: randomized phase III trial of
trastuzumab plus docetaxel with or without carboplatin first line in HER2 positive metastatic
breast cancer (MBC). ASCO. 2006;Abstract #LBA516.
Leyland-Jones B, Gelmon K, Ayoub JP, et al. Pharmacokinetics, safety, and efficacy of
trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol.
2003;21:3965-3971.
Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of
trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor
2–positive metastatic breast cancer administered as first-line treatment: The M77001 Study
Group. J Clin Oncol. 2005;23:4265-4274.
Tedesco KL, Thor AD, Johnson DH, et al. Docetaxel combined with trastuzumab is an active
regimen in HER2-3+ and overexpressing and fluorescent in situ hybridization-positive metastatic
breast cancer: a multi-institutional phase II trial. J Clin Oncol. 2004;22:1071-1077.
19 Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for low emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended. For anemia* If hemoglobin level is less than 10 g/dl, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For hypersensitivity To prevent hypersensitivity reactions, consider one of the following before the start of chemotherapy administration: 


dexamethasone 8 mg P.O. twice daily for 3 days starting 1 day before chemotherapy, or 20 mg P.O. 12 hours and 6 hours before chemotherapy, or 20 mg I.V. before chemotherapy diphenhydramine 50 mg I.V. 30 to 60 minutes before chemotherapy cimetidine 300 mg I.V. or ranitidine 50 mg I.V. 30 to 60 minutes before chemotherapy Epirubicin Metastatic or recurrent disease therapy Regimen Details Epirubicin 60 to 90 mg/m2 I.V. on day 1
Repeat cycle every 21 days.
References:
20 Bastholt L, Dalmark M, Gjedde SB, et al. Dose-response relationship of epirubicin in the
treatment of postmenopausal patients with metastatic breast cancer: a randomized study of
epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative
Group. J Clin Oncol. 1996;14:1146-1155.
Perez DJ, Harvey VJ, Robinson BA, et al. A randomized comparison of single-agent doxorubicin
and epirubicin as first-line cytotoxic therapy in advanced breast cancer. J Clin Oncol.
1991;9:2148-2152.
Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for moderate emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended as needed. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. Hormone therapy Adjuvant and neoadjuvant therapy (tamoxifen, anastrozole, exemestane, letrozole) Metastatic disease therapy (tamoxifen, anastrozole, exemestane, letrozole) Prevention therapy (tamoxifen, raloxifene) Biomarker Testing: ER receptor Regimen Details Tamoxifen
For adjuvant therapy and metastatic disease therapy
Tamoxifen 20 mg P.O. daily (divide doses greater than 20 mg/day into two doses)
Anastrozole
For adjuvant therapy and metastatic disease therapy
Anastrozole 1 mg P.O. daily
Exemestane
For adjuvant therapy and metastatic disease therapy
Exemestane 25 mg P.O. daily (after a meal)
Letrozole
For adjuvant therapy and metastatic disease therapy
Letrozole 2.5 mg P.O. daily
21 Raloxifene
For prevention
Raloxifene 60 mg P.O. daily
References:
References for tamoxifen
Beex L, Rose C, Mouridsen H, et al. Continuous versus intermittent tamoxifen versus
intermittent/alternated tamoxifen and medroxyprogesterone acetate as first line endocrine
treatment in advanced breast cancer: An EORTC phase III study (10863). Eur J Cancer.
2006;42:3178-3185.
Crump M, Sawka, CA, DeBoer G, et al. An individual patient-based meta-analysis of tamoxifen
versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic
breast cancer. Breast Cancer Res Treat. 1997;44:201-210.
Deshmane V, Krishnamurthy S, Melemed AS, et al. Phase III double-blind trial of arzoxifene
compared with tamoxifen for locally advanced or metastatic breast cancer. J Clin Oncol.
2007;25:4967-4973.
International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for
premenopausal women with lymph node-positive breast cancer: International Breast Cancer
Study Group Trial 13-93. J Clin Oncol. 2006;24:1332-1341.
Killander F, Anderson H, Ryden S, et al. Radiotherapy and tamoxifen after mastectomy in
postmenopausal women – 20 year follow-up of the South Sweden Breast Cancer group
randomised trial SSBCG II:I. Eur J Cancer. 2007;43:2100-2108.
References for anastrozole
The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group. Anastrozole
alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of
postmenopausal women with early breast cancer: first results of the ATAC randomised trial.
Lancet. 2002;359:2131-2139.
The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group. Effect of
anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month
analysis of the ATAC trial. Lancet Oncol. 2008;9:45-53.
The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group. Results of the
ATAC trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet.
2005;365:60-62.
Boccardo F, Rubagotti A, Puntoniet M, et al. Switching to anastrozole versus continued
tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen
Anastrozole Trial. J Clin Oncol. 2005;23:5138-5147.
Bonneterre J, Busdar A, Nabholtz JA, et al. Anastrozole is superior to tamoxifen as first-line
therapy in hormone receptor–positive advanced breast carcinoma: Results of two randomized
trials designed for combined analysis. Cancer. 2001;92:2247-2258.
22 Bonneterre J, Thürlimann B, Robertson JFR, et al. Anastrozole versus tamoxifen as first-line
therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or
Arimidex Randomized Group Efficacy and Tolerability Study. J Clin Oncol. 2000;18:37483757.
Cuzick J, Sestak I, Baum M, et al. ATAC/LATTE investigators. Effect of anastrozole and
tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC
trial. Epub 2010 Nov 17. Lancet Oncol. 2010 Dec;11(12):1135-1141.
Jonat W, Gnant M, Boccardo F, et al. Effectiveness of switching from adjuvant tamoxifen to
anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a metaanalysis. Lancet Oncol. 2006;7:991-996.
Nabholtz JM, Buzdar A, Pollak M, et al. Anastrozole is superior to tamoxifen as first-line
therapy for advanced breast cancer in postmenopausal women: results of a North American
multicenter randomized trial. J Clin Oncol. 2000;18:3758-3767.
Winer EP, Hudis C, Burstein HJ, et al. American Society of Clinical Oncology Technology
Assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women
with hormone receptor–positive breast cancer: status report 2004. J Clin Oncol. 2005;23:619629.
References for exemestane
Chia S, Gradishar W, Mauriac L, et al. Double-blind, randomized placebo controlled trial of
fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in
postmenopausal women with hormone receptor–positive, advanced breast cancer: results from
EFECT. J Clin Oncol. 2008;26:1664-1670.
Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of exemestane after two to three years
of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med.
2004;350:1081-1092.
Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus
tamoxifen after 2–3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised
controlled trial. Lancet. 2007;369:559-570.
Dirix LY, Ignacio J, Nag S, et al. Treatment of advanced hormone-sensitive breast cancer in
postmenopausal women with exemestane alone or in combination with celecoxib. J Clin Oncol.
2008;26:1253-1259.
Goss PE, Ingle JN, Alés-Martínez JE, et al. NCIC CTG MAP.3 Study Investigators. Exemestane
for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):23812391. Epub 2011 Jun 4.
Jones SE, Cantrell J, Vukelja S, et al. Comparison of menopausal symptoms during the first year
of adjuvant therapy with either exemestane or tamoxifen in early breast cancer: report of a
tamoxifen exemestane adjuvant multicenter trial substudy. J Clin Oncol. 2007;25:4765-4771.
23 Mamounas EP, Jeong J-H, Wickerham DL, et al. Benefit from exemestane as extended adjuvant
therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical
Adjuvant Breast and Bowel Project B-33 Trial. J Clin Oncol. 2008;26:1965-1971.
Mlineritsch B, Tausch C, Singer C, et al. Exemestane as primary systemic treatment for hormone
receptor positive post-menopausal breast cancer patients: a phase II trial of the Austrian Breast
and Colorectal Cancer Study Group (ABCSG-17). Breast Cancer Res Treat. 2007;Epub Dec 22.
References for letrozole
The Breast International Group (BIG) 1-98 Collaborative Group. A comparison of letrozole and
tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353:27472757.
Goss P, Bondarenko IN, Manikhas GN, et al. Phase III, double-blind, controlled trial of
atamestane plus toremifene compared with letrozole in postmenopausal women with advanced
receptor-positive breast cancer. J Clin Oncol. 2007;25:4961-4966.
Goss P, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women
after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med.
2003;349:1793-1802.
Krainick-Strobel UE, Lichtenegger W, Wallwiener D, et al. Neoadjuvant letrozole in
postmenopausal estrogen and/or progesterone receptor–positive breast cancer: a phase IIb/III
trial to investigate optimal duration of preoperative endocrine therapy. BMC Cancer. 2008;8:62.
Mouridsen H. Letrozole in advanced breast cancer: the PO25 trial. Breast Cancer Res Treat.
2007;105(suppl 1):19-29.
Mouridsen H, Gershanovich M, Sun Y, et al. Phase III study of letrozole versus tamoxifen as
first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and
update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol.
2003;21:2101-2109.
Winer EP, Hudis C, Burstein HJ, et al. American Society of Clinical Oncology Technology
Assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women
with hormone receptor–positive breast cancer: status report 2004. J Clin Oncol. 2005;23:619629.
References for raloxifene
Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and
breast cancer in postmenopausal women. N Engl J Med. 2006;355:125-137.
Dickler MN, Norton L. The MORE Trial: multiple outcomes for raloxifene evaluation: breast
cancer as a secondary end point: implications for prevention. Ann NY Acad Sci. 2001:949:134142.
Land SR, Wickerham DL, Costantino JP, et al. Patient-reported symptoms and quality of life
during treatment with tamoxifen or raloxifene for breast cancer prevention: the NSABP study of
tamoxifen and raloxifene (STAR) P-2 trial. JAMA. 2006;295:2742-2751.
24 Lippman ME, Cummings SR, Disch DP, et al. Effect of raloxifene on the incidence of invasive
breast cancer in postmenopausal women with osteoporosis categorized by breast cancer risk.
Clin Cancer Res. 2006;12:5242-5247.
Martino S, Cauley JA, Barrett-Connor E, et al. Continuing outcomes relevant to Evista: breast
cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J
Natl Cancer Inst. 2004;96:1751-1761.
Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of
developing invasive breast cancer and other disease outcomes: the NSABP Study of tamoxifen
and raloxifene (STAR) P-2 trial. JAMA. 2006;295:2727-2741.
Supportive Therapy General support Supportive therapy guidelines and risk of complications due to Hormone therapy drugs for breast cancer may differ significantly from chemotherapy drug regimens for breast cancer. Some common high risk complications across this class of drugs include increased cholesterol (letrozole, anastrozole), increased potential for blood clots (raloxifene, tamoxifen, anastrozole, letrozole), tumor flare up (raloxifene, tamoxifen), and decreased bone mineral density (anastrozole, exemestane, letrozole). Monitor these patients closely for adverse reactions and consider appropriate treatment for prevention and incidence according to the patients’ condition, treatment therapies and disease type. Ixabepilone (with or without capecitabine) Metastatic or recurrent disease therapy Regimen Details Ixabepilone 40 mg/m2 I.V. on day 1
With or without
Capecitabine 2,000 mg/m2/day (in two divided doses) P.O. on days 1 to 14
Repeat cycle every 21 days.
References:
Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase
II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and
capecitabine. J Clin Oncol. 2007;25:3407-3414.
Roche H, Yelle L, Cognetti F, et al. Phase II clinical trial of ixabepilone (BMS-247550), an
epothilone B analog, as first-line therapy in patients with metastatic breast cancer previously
treated with anthracycline chemotherapy. J Clin Oncol. 2007;25:3415-3420.
Thomas E, Gomez HL, Li RK, et al. Ixabepilone plus capecitabine for metastatic breast cancer
progressing after anthracycline and taxane treatment. J Clin Oncol. 2007;25:5210-5217.
Thomas E, Tabernero J, Fornier M, et al. Phase II clinical trial of ixabepilone (BMS-247550), an
epothilone B analog, in patients with taxane-resistant metastatic breast cancer. J Clin Oncol.
2007;25:3399-3406.
25 Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for low emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens may be recommended. For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For diarrhea Follow the National Cancer Institute’s guidelines for grading and treating diarrhea based on severity of symptoms on a scale of 1 (mild) to 4 (severe or life‐threatening). Lapatinib, capecitabine Metastatic or advanced HER2‐overexpressing breast cancer Biomarker Testing: HER2 Regimen Details Lapatinib 1250 mg P.O. on days 1 to 21
Capecitabine 2000 mg/m2/day (in two divided doses approximately 12 hours apart) P.O. on days
1 through 14
Repeat cycle every 21 days.
26 References:
Cameron D, Casey M, Press M, et al. A phase III randomized comparison of lapatinib plus
capecitabine versus capecitabine alone in women with advanced breast cancer that has
progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat.
2008;Epub January 11.
Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced
breast cancer. N Engl J Med. 2006;355:2733-2743.
Greil R, Borštnar S, Petráková K, et al. Combination therapy of lapatinib and capecitabine for
ErbB2-positive metastatic or locally advanced breast cancer: results from the Lapatinib
Expanded Access Program (LEAP) in Central and Eastern Europe. Onkologie. 2011;34(5):233238. Epub 2011 Apr 26.
Supportive Therapy For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For diarrhea Follow the National Cancer Institute’s guidelines for grading and treating diarrhea based on severity of symptoms on a scale of 1 (mild) to 4 (severe or life‐threatening). Paclitaxel Metastatic or recurrent disease therapy 27 Regimen Details Paclitaxel 175 or 250 mg/m2 I.V. over 3 hours on day 1
Repeat cycle every 21 days.
Or
Paclitaxel 80 mg/m2 I.V. over 1 hour on day 1
Repeat cycle every 7 days.
References:
Bishop JF, Dewar J, Toner GC, et al. Initial paclitaxel improves outcome compared with CMFP
combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin
Oncol. 1999;17:2355-2364.
Perez EA, Vogel CL, Irwin DH, et al. Multicenter phase II trial of weekly paclitaxel in women
with metastatic breast cancer. J Clin Oncol. 2001;19:4216-4223.
Seidman AD, Berry D, Cirrincione C, et al. CALGB 9840: Phase III study of weekly (W)
paclitaxel (P) via 1-hour(h) infusion versus standard (S) 3h infusion every third week in the
treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and
randomized for T in HER2 normal MBC. ASCO 2004;Abstract #512.
Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of weekly compared with
every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2
overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final
results of Cancer and Leukemia Group B Protocol 9840. J Clin Oncol. 2008;26:1642-1649.
Seidman AD, Tiersten A, Hudis C, et al. Phase II trial of paclitaxel by 3-hour infusion as initial
and salvage chemotherapy for metastatic breast cancer. J Clin Oncol. 1995;13:2575-2581.
Sledge GW, Neuberg D, Bernardo P, et al. Phase III trial of doxorubicin, paclitaxel, and the
combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast
cancer: an Intergroup Trial (E1193). J Clin Oncol. 2003;21:588-592.
Smith RE, Brown AM, Mamounas EP, et al. Randomized trial of 3-hour versus 24-hour infusion
of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National
Surgical Adjuvant Breast and Bowel Project Protocol B-26. J Clin Oncol. 1999;17:3403-3411.
Verrill MW, Lee J, Cameron DA, et al. Anglo-Celtic IV: first results of a UK National Cancer
Research Network randomised phase 3 pharmacogenetic trial of weekly versus 3 weekly
paclitaxel in patients with locally advanced or metastatic breast cancer (ABC). ASCO
2007;Abstract #LBA1005.
Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for low emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens may be recommended as needed. 28 For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



cepoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. cepoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. cdarbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. cdarbepoetin alfa 500 mcg subcutaneously every 3 weeks *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For diarrhea Follow the National Cancer Institute’s guidelines for grading and treating diarrhea based on severity of symptoms on a scale of 1 (mild) to 4 (severe or life‐threatening). For hypersensitivity reactions To prevent hypersensitivity reactions, consider one of the following before the start of chemotherapy administration: 


dexamethasone 8 mg P.O. twice daily for 3 days starting 1 day before chemotherapy, or 20 mg P.O. 12 hours and 6 hours before chemotherapy, or 20 mg I.V. before chemotherapy diphenhydramine 50 mg I.V. 30 to 60 minutes before chemotherapy cimetidine 300 mg I.V. or ranitidine 50 mg I.V. 30 to 60 minutes before chemotherapy Paclitaxel, trastuzumab Recurrent or metastatic HER2‐overexpressing breast cancer Biomarker Testing: HER2 Regimen Details Paclitaxel 175 mg/m2 I.V. over 3 hours on day 1
Repeat cycle every 21 days.
29 With
Trastuzumab 8 mg/kg I.V. over 90 minutes on day 1 of first cycle
Followed by
6 mg/kg I.V. over 30 minutes every 21 days
Or
Paclitaxel 80 to 90 mg/m2 I.V. weekly
With
Trastuzumab 4 mg/kg I.V. over 90 minutes on day 1 of first week
Followed by
2 mg/kg I.V. over 30 minutes weekly
References:
Leyland-Jones B, Gelmon K, Ayoub J-P, et al. Pharmacokinetics, safety, and efficacy of
trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol.
2003;21:3965-3971.
Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of weekly compared with
every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2
overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final
results of Cancer and Leukemia Group B Protocol 9840. J Clin Oncol. 2008;26:1642-1649.
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody
against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med.
2001;344:783-792.
Supportive Therapy For nausea and vomiting On day 1 of each cycle or day 1 of weekly regimen, follow acute‐onset antiemetic regimen for low emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens may be recommended. For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. 30 For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For hypersensitivity reactions To prevent hypersensitivity reactions, consider one of the following before the start of chemotherapy administration: 


dexamethasone 8 mg P.O. twice daily for 3 days starting 1 day before chemotherapy, or 20 mg P.O. 12 hours and 6 hours before chemotherapy, or 20 mg I.V. before chemotherapy diphenhydramine 50 mg I.V. 30 to 60 minutes before chemotherapy cimetidine 300 mg I.V. or ranitidine 50 mg I.V. 30 to 60 minutes before chemotherapy TC (docetaxel [Taxotere], cyclophosphamide) Adjuvant therapy Regimen Details Docetaxel 75 mg/m2 I.V. on day 1
Cyclophosphamide 600 mg/m2 I.V. on day 1
Repeat cycle every 21 days for four cycles.
References:
Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus
cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable
breast cancer. J Clin Oncol. 2006;24:5381-5387.
Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for moderate emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended. For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 


epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. 31 
darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For hypersensitivity reactions To prevent hypersensitivity reactions, consider one of the following before the start of chemotherapy administration: 


dexamethasone 8 mg P.O. twice daily for 3 days starting 1 day before chemotherapy, or 20 mg P.O. 12 hours and 6 hours before chemotherapy, or 20 mg I.V. before chemotherapy diphenhydramine 50 mg I.V. 30 to 60 minutes before chemotherapy cimetidine 300 mg I.V. or ranitidine 50 mg I.V. 30 to 60 minutes before chemotherapy TCH → (Docetaxel [Taxotere]/Carboplatin, Trastuzumab [Herceptin]) Adjuvant therapy for HER2‐overexpressing breast cancer Biomarker Testing: HER2 (trastuzumab) Regimen Details Docetaxel 75 mg/m2 I.V. on day 1
Carboplatin AUC 6 I.V. on day 1
Repeat cycle every 21 days for six cycles.
with
Trastuzumab 4 mg/kg I.V. over 90 minutes week 1
Followed by
Trastuzumab 2 mg/kg I.V. over 30 minutes weekly for 17 weeks
Followed by
Trastuzumab 6 mg/kg I.V. over 30 to 90 minutes every 21 days to complete 52 weeks of
trastuzumab.
References:
Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer.
N Engl J Med. 2011; 365: 1273-1283.
32 Supportive Therapy For nausea and vomiting On day 1, follow acute‐onset antiemetic regimen for moderate emetic risk. Anticipatory, breakthrough, and delayed‐onset regimens are recommended. For anemia* If hemoglobin level is less than 10 g/dL, iron I.V. is recommended. For anemia secondary to myelosuppressive chemotherapy in noncurative patients, one of the following is recommended: 



epoetin alfa 150 units/kg subcutaneously three times weekly. If unsatisfactory response, may increase to 300 units/kg subcutaneously three times weekly. epoetin alfa 40,000 units subcutaneously weekly. If unsatisfactory response, may increase to 60,000 units weekly. darbepoetin alfa 2.25 mcg/kg subcutaneously every week. If unsatisfactory response, may increase to 4.5 mcg/kg subcutaneously every week. darbepoetin alfa 500 mcg subcutaneously every 3 weeks. *Erythropoiesis‐stimulating agents (ESAs) are not indicated if therapy is administered with curative intent. If this regimen is used as adjvant therapy for limited stage disease, the use of an ESA is not appropriate. For neutropenia To prevent or treat neutropenia, one of the following is recommended: 


filgrastim 5 mcg/kg (rounded to the nearest vial size by institution‐defined weight limits) subcutaneously daily, continued through postnadir recovery pegfilgrastim 6 mg subcutaneously as a single dose per treatment cycle sargramostim 250 mcg/m2/day subcutaneously, continued through postnadir recovery Start colony‐stimulating factors 24 to 72 hours after chemotherapy ends. Note: Although all of the above drugs can be given I.V., the subcutaneous route is preferred. For diarrhea Follow the National Cancer Institute’s guidelines for grading and treating diarrhea based on severity of symptoms on a scale of 1 (mild) to 4 (severe or life‐threatening). For infusion reactions Consider premedication with acetaminophen, dexamethasone, and diphenhydramine to prevent infusion reactions. For peripheral neuropathy To treat peripheral neuropathy, consider over‐the‐counter pain relievers and gabapentin, as appropriate. Antidepressants, such as tricyclics and a selective serotonin and norepinephrine reuptake inhibitor (duloxetine hydrochloride), may provide some benefit. For pain, give opiate analgesics. 33