TIP regimen (paclitaxel, ifosfamide, cisplatin) in nonseminomatous germ cell tumors with poor-prognosis and unfavorable decline of serum tumor markers: final results

Background: Patients with germ cell tumors (GCTs) and poor-prognosis demonstrate unsatisfactory oncological outcomes, with a one-year progression-free survival (PFS) rate of approximately 50 %. We hypothesized that switching the chemotherapy regimen to TIP (paclitaxel, ifosfamide (mesna), cisplatin) in cases of unfavorable decline of serum tumor markers (STMs) after the first cycle of BEP (bleomycin, etoposide, cisplatin) could improve treatment outcomes in this subgroup of patients.Materials and methods: A multicenter, prospective, non-randomized phase II study included patients with nonseminomatous GCTs and poor-prognosis according to IGCCCG. All patients received the first cycle of chemotherapy in BEP regimen. Patients with an unfavorable decline of STMs subsequently received 4 cycles of TIP regimen (paclitaxel 120 mg / m² on days 1 and 2 + ifosfamide 1500 mg / m² on days 2-5 (+ mesna) + cisplatin 25 mg / m² on days 2-5 + G-CSF). In the presence of residual tumors larger than 1 cm and the technical feasibility of removal, surgical treatment was performed. The primary endpoint was one-year PFS.Results: From 2017 to 2023, 34 patients were included in the study. Enrollment was prematurely closed due to an extremely low likelihood of achieving the primary endpoint. One-year PFS and overall survival (OS) were 57.1 % and 74.4 %, respectively. The favorable response rate (complete response + partial response with normalization STM) was observed in 55,8 % of patients. Disease progression was observed in 21 patients, with the central nervous system being the first site of progression in 8 (37 %) of them. Surgical treatment was performed in 16 patients, with viable tumor obtained in 4 patients. Conducting the first cycle in a “stabilization» mode for ultra-high-risk patients did not affect PFS (p = 0.28) or OS (p = 0.434). The toxicity profile of the TIP regimen was acceptable.Conclusion: Switching from BEP to TIP for patients with nonseminomatous GCTs and an unfavorable decline of STMs did not demonstrate efficacy. Further exploration of alternative therapeutic approaches is needed to improve treatment outcomes.