Four Cycles of Etoposide plus Cisplatin for Patients with Good‐Risk Advanced Germ Cell Tumors – The Oncologist

Background

The National Comprehensive Cancer Network recommends either three cycles of bleomycin, etoposide, and cisplatin (BEPx3) or four cycles of etoposide and cisplatin (EPx4) as initial chemotherapy for the treatment of good‐risk germ cell tumors (GCT). To assess the response, toxicity, and survival outcomes of EPx4, we analyzed our experience.

Material and Methods

Response and survival outcomes, selected toxicities, and adherence to chemotherapy dose and schedule were assessed in good‐risk GCT patients who received EPx4 followed by adjunctive surgery at Memorial Sloan Kettering Cancer Center between 1982 and 2016. The results were compared to our past results and recently published data.

Results

Between 1982 and 2016, 944 GCT patients were treated with EPx4, 289 who were previously reported plus 655 treated between January 2000 and August 2016. A favorable response was achieved in 928 of 944 patients (98.3%). Five‐year progression‐free, disease‐specific, and overall survival rates were 93.9%, 98.6%, and 97.9%, respectively. Median follow‐up was 7.3 years (range, 2.8 months to 35.5 years). Viable, nonteratomatous malignant GCT was present in 3.5% of 432 post‐chemotherapy retroperitoneal lymph node dissection specimens from patients with nonseminomatous GCT. Febrile neutropenia and thromboembolic events occurred in 16.0% and 8.9%, respectively, with one treatment‐related death. In the more recent 655 patient cohort, full‐dose EPx4 was administered to 631 (96.3%), with deviations from planned treatment driven mainly by vascular (n=13), hematologic (n=11), renal (n=7), or infectious (n=5) events.

Conclusion

EPx4 is highly effective and well‐tolerated in patients with good‐risk GCT, and remains a standard of care.

Implications for Practice

EPx4 is a standard‐of‐care regimen for all patients with good‐risk GCT with a favorable response rate and disease‐specific survival of 98%. Full‐dose administration of etoposide and cisplatin and complete resection of residual disease lead to optimal outcomes. EPx4 should be the recommended regimen in active smokers, patients with reduced or borderline kidney function, and patients over age 50, which are patient groups at increased risk for bleomycin pulmonary toxicity. Due to a risk of acquired severe pulmonary illness, EPx4 may also be favored for patients who vape or use e‐cigarettes, and during ongoing transmission of SARS‐CoV‐2.