Carboplatin (AUC 5) with oral vinorelbine (VNR) d 1,8 at 50 mg/m2 (level 1, L1) or 60 mg/m2 (level 2, L2) every 3 weeks: A phase I study

Abstract

5114 Background & Objectives: We sought to develop a less toxic combination regimen for use in cervical cancer than cisplatin with paclitaxel. Carboplatin AUC 5 and VNR D1 (IV, 25 mg/m2) & D8 (PO, 60 mg/m2) have been previously studied in chemonaive non-small cell lung cancer (O’Brien et al, Ann Oncol 2004; 15: 921). Methods: Metastatic solid tumor cohort, 3+3 dose escalation design, with standard entry/evaluation criteria and separate escalation based on extent of prior treatment. Common Toxicity Criteria V.3 were applied. Results: L1 accrued 3 extensively pre-treated patients (= or > 3 myelosuppressive regimens and/or radiation): all progressed after 2 cycles with no Grade 3 or 4 toxicities, one Grade 2 neutropenia. At L2, 6 extensively pretreated were evaluable, 1 minimally pre-treated was inevaluable due to withdrawal of consent after C1,d1. Myelosuppression was the prominent toxicity after 2, 2+, 2+, 2+, 3, 8 + cycles. Table 1 shows all hematologic toxicities at L2 dosing level of the 6 evaluable patients. The patient with dose-limiting thrombocytopenia had similar episodes on prior chemotherapy. Responses: 3 patients had stable disease with subjective or marker improvement: breast cancer (1), endometrial cancer (1), and granulosa cell tumor (1). One prostate cancer patient received 8+ cycles, with slowly rising PSA. Conclusions: L2 is the recommended phase II dose and may be suitable for Phase II study in cervical cancer, with potential advantages over IV vinorelbine (absence of phlebitis, decreased tumor pain). No significant financial relationships to disclose.