Paclitaxel plus BEP (T-BEP) regimen as induction chemotherapy (CT) in nonseminomatous germ cell tumors (NSGCT) patients with poor prognosis: A phase II study.

Abstract

4587 Background: Paclitaxel is an active drug in the treatment of patients (pts) with NSGCT. We performed a phase II study to assess the efficacy and toxicity of T-BEP regimen in the first line treatment of NSGCT pts with poor prognosis. Methods: CT-naïve NSGCT pts with poor prognosis (IGCCCG) received T-BEP as follows: paclitaxel 175 mg/m2 d 2, cisplatin 20 mg/m2 d 1-5, etoposide 100 mg/m2 d1-5, bleomycin 30 IU d 1,3,5 with G-CSF support 300 mcg d 6-15. Four–six cycles of CT were administered depending on time to normalization of tumor markers. The primary endpoint was the progression free rate at 1-year after completion of CT. The hypotheses being tested was Ho: p0 = pexp (p0=0.50). Assuming pexp=0.70 with a two-sided type I error of 0.05, a type II error of 0.2 and 10% of pts drop-out rate, 51 pts were required. Results: From 2004 to 2008, 51 pts were treated. Sixteen (30%) pts had primary mediastinal tumor. Median follow-up (f.-up) of survived pts was 26 months (range, 6 – 54). Complete response (CR) after CT and surgery was achieved in 11 (22%) pts. Twenty eight (55%) pts had partial response (PR) marker “-“ status, 3 (6%) pts – PR marker “+”, and 9 (17%) pts were classified as treatment failure (progression disease or incomplete resection of viable tumor). When 27 pts had been treated, an unplanned analysis showed inappropriate toxicity on cycle 1 (6 pts had infection gr. 3/4, which resulted in two toxic deaths). Thereafter, the regimen was modified: the next 26 pts started BEP regimen on cycle 1 followed by T-BEP on subsequent cycles. No more severe infections or toxic deaths were observed in the cohort. For all pts, toxicity (grade 3/4) included neutropenia 70%, febrile neutropenia 34%, mucositis 4% and diarrhea 2%. A patient was lost for follow-up (follow-up <1 year) and efficacy was assessed in 50 pts. At 1-year after completion of CT 26 (58%) pts were free of disease, which was compatible with results of BEP alone. Conclusions: T-BEP regimen does not improve outcome of NSGCT pts with poor prognosis. No significant financial relationships to disclose.