Carboplatin-etoposide combination chemotherapy in metastatic castration-resistant prostate cancer: A retrospective study

Introduction

Prostate cancer is the second most frequently diagnosed type of cancer and the sixth leading cause of cancer-related mortality in men, accounting for 14% (903,500) of total new cancer cases and 6% (258,400) of total cancer deaths in men in 2008 (1). The treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) is changing rapidly and numerous treatments are available. In heavily preteated patients, neuroendocrine transdifferentiation may be a mechanism of treatment escape (2–5). The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differentiated neuroendocrine cancers, such as small-cell lung cancer (6). Of note, the combination of carboplatin and etoposide has provided encouraging results in mCRPC. In a phase II trial by Loriot et al (7) assessing the combination of carboplatin [area under the curve (AUC)=5 on day 1] and etoposide (80 mg/m²/day, intravenous infusion on days 1–3) following first-line treatment with docetaxel, the response rate was 23%, the median progression-free survival (PFS) was 2.1 months (range, 0.6–9.6 months) and the median overall survival (OS) was 19 months (range, 2.1–27.7 months). A phase II trial by Fléchon et al (8) investigating patients with anaplastic progressive mCRPC assessed carboplatin (AUC=4 on day 1) and etoposide (100 mg/m²/day as an intravenous infusion on days 1–3). The response rate was 8.9%, the PFS was 2.9 months [95% confidence interval (CI): 1.7–3.5] and the median OS was 9.6 months (95% CI: 8.7–12.7).

Prolonged fractionated oral administration of etoposide may provide a theoretical advantage in terms of toxicity over intravenous administration of a bolus dose. A phase I trial by Thiery-Vuillemin et al (9) evaluating the combination of carboplatin (AUC=5 on day 1) and oral etoposide (25 mg, 3 times daily) in 19 patients with varied solid tumors, 3 of whom had prostate cancer, reported an acceptable toxicity profile.

In the University Hospital of Besançon, administration of carboplatin-etoposide, orally or intravenously, has been used for heavily pretreated patients with mCRPC. This retrospective study aimed to assess the efficacy and tolerability of this regimen and compare the efficacy and tolerability of carboplatin plus oral etoposide vs. carboplatin plus intravenous etoposide.

Patients and methods

Study population

The Bonne Pratiques de Chimiothérapie (BPC®) software, which is a computer software for chemotherapy prescription from...