786P - A phase II trial of paclitaxel, ifosfamid and cisplatin in patients with poor-prognosis disseminated non-seminomatous germ cell tumors with unfavorable serum tumor marker decline after first cycle of chemotherapy

Background

Germ cell tumors represents highly curable disease even in metastatic stage. However, poor risk patients with unfavorable serum tumor marker decline after first cycle of chemotherapy represents subgroup with dismal prognosis with approximately 50% cure rate with BEP (bleomycin, etoposide and cisplatin). Dose-dense chemotherapy regimen improved progression-free survival in this setting, at the cost of increased toxicity. The aim of this study was to determine the efficacy and safety of paclitaxel, ifosfamid and cisplatin (TIP) in this patient’s population.

Methods

Poor prognosis patients according to IGCCCG classification with unfavorable serum tumor marker decline after first cycle of chemotherapy were included in this phase II study (NCT02414685). Treatment regimen consisted of paclitaxel 250 mg/m² on day 1, ifosfamid 1200 mg/m² days 1-5 and cisplatin 20 mg/m² days 1-5, totally for 4 cycles. Primary endpoint was complete response (CR) rate. The Simon´s 2-stage design was used. More than 6 CR to study therapy among the first 19 patients was needed to proceed to second stage.

Results

From November 2015 to January 2020, 19 patients with a median age of 30 years (range, 24 to 44 years) were enrolled. Non-pulmonary visceral metastases had 11 (57.9%) of patients, while S3 disease had 17 (89.5%) of them. CR was achieved in 4 (21.1%) patients, therefore study was terminated in the first stage. Favorable response rate (CR or partial remission with negative tumor markers) was observed in 15 (78.9%) patients. At a median follow-up period of 16.7 months (range, 4.1 to 51.3), 10 (52.6%) patients experienced disease progression, and 6 patients (31.6%) died. The 2-year PFS and OS was 41.2% (95% CI 16.8 – 65.7) and 72.7% (95% CI 48.9 – 96.4), respectively. TIP was well tolerated, and no unexpected toxicity was observed.

Conclusions

Treatment modification from BEP to TIP regimen in patients with unfavorable serum tumor marker decline after first cycle of chemotherapy was not associated with improved outcome and four cycles of BEP, remains the standard treatment option in this patients population.

Clinical trial identification

NCT02414685.

Editorial acknowledgement

Legal entity responsible for the study

National Cancer Institute, Slovakia.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.