Oleh Admin Kalbe Medical pada August 01, 2017 07:30

Weekly Carboplatin-Paclitaxel pada Pasien Kanker Payudara Metastatik

Kanker payudara metastatik termasuk penyakit incurable walaupun telah terdapat perbaikan survival dalam beberapa tahun terakhir, terutama setelah dikenalkannya terapi target pada pasien dengan human epidermal growth factor receptor 2 (HER2) positif dan reseptor hormon positif. Kemoterapi sistemik masih menjadi satu pilihan terapi terpilih untuk semua subtipe kanker payudara metastatik dan satu-satunya terapi yang efektif untuk kanker payudara tripel negatif. Taxane, termasuk paclitaxel, docetaxel, dan nanoparticle albumin-bound paclitaxel, merupakan terapi yang di antaranya efektif untuk kanker payudara metastatik. Paclitaxel weekly dan docetaxel triweekly merupakan regimen taxane yang sering digunakan, dengan objective response rate (ORR) yang dilaporkan sebesar 25,6-42,6% dan median progression free survival (PFS) 5,7-9 bulan.

Suatu meta-analisis menunjukkan adanya manfaat overall survival (OS) dengan kombinasi yang mengandung taxane dibandingkan taxane tunggal. Triweekly carboplatin-paclitaxel menunjukkan aktivitas anti-tumor menjanjikan, tetapi dengan toksisitas bermakna. Studi fase II pada pasien kanker payudara stadium lanjut menunjukkan manfaat response rate 54-62% dengan median PFS 7,3-8,6 bulan. Efek samping derajat 3-4 yang sering antara lain leukopenia, neutropenia, dan trombositopenia.

Weekly carboplatin-paclitaxel telah digunakan sebagai terapi adjuvan kanker payudara HER2 positif dalam kombinasi dengan trastuzumab dan menunjukkan aktivitas dalam setting terapi kanker payudara tripel negatif. Peneliti melakukan studi retrospektif untuk mengevaluasi aktivitas anti-tumor dan keamanan weekly carboplatin-paclitaxel pada pasien kanker payudara metastatik di suatu institusi di Italia selama tahun 2007 sampai 2016. Pasien mendapat terapi carboplatin AUC 2 plus paclitaxel 80 mg/m2, keduanya diberikan hari 1 dan 8 setiap 21 hari.

Hasil dari studi (n= 274) yang dilakukan dengan median siklus terapi 6 siklus, antara lain ORR sebesar 44,7%, median PFS 8,6 bulan, median OS 23,7 bulan. Pasien dengan kanker payudara tripel negatif memiliki PFS (6,7 bulan vs 8,6 bulan vs 9,65 bulan) dan OS (19,5 bulan vs 23 bulan vs 28,2 bulan) yang lebih pendek dibandingkan kelompok biologi lain (reseptor hormon positif HER2 negatif; HER2 positif). Dalam analisis multivariable, riwayat taxane sebelumnya, reseptor hormon positif HER2 negatif, metastatik yang lebih banyak, dan metastatik de novo saat diagnosis dikaitkan dengan penurunan PFS, sedangkan mendapatkan terapi pemeliharaan dikaitkan dengan perbaikan PFS. Terapi ditoleransi dengan cukup baik, dengan 10,2% dari pasien menghentikan satu atau kedua terapi karena efek samping. Neutropenia derajat 3-4 dijumpai pada 16,8% dari pasien dan demam neutropenia dijumpai pada 2,3% dari pasien. Mual dan muntah dijumpai pada 33,3% dari pasien.

Dalam diskusi disebutkan baik kekuatan maupun limitasi dari studi ini. Kekuatan dari studi ini adalah pasien monosentrik, tersedianya rekam medik yang detail, dan tingginya kejadian PFS relatif terhadap jumlah total pasien. Limitasi dari studi ini yaitu desainnya retrospektif, jumlah pasien yang terbatas, dan jumlah pasien yang dengan biologi tumor berbeda. Sampai permasalahan agen tunggal dan kombinasi menjadi jelas, penggunaan kombinasi kemoterapi harus didiskusikan dengan pasien dan potensi manfaat dibandingkan risiko harus dipertimbangkan.

Kesimpulan dari studi ini adalah regimen weekly carboplatin-paclitaxel aktif dan ditoleransi dengan baik untuk terapi kanker payudara metastatik. Studi prospektif yang membandingkan dengan paclitaxel atau docetaxel serta regimen kombinasi lainnya masih diperlukan. (HLI)

Image : Ilustrasi
Referensi:
1.Vernieri C, Milano M, Mennitto A, Maggi C, Ferrari B, Rinaldi L, et al. Antitumor activity and safety profile of weekly carboplatin plus paclitaxel in metastatic breast cancer: A ten-year, monocentric, retrospective study. Breast Cancer Res Treat. 2017 doi: 10.1007/s10549-017-4336-z.
2.Pentheroudakis G, Razis E, Athanassiadis A, Pavlidis N, Fountzilas G. Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer. Medical Oncology 2006;23(2):147-60.

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