Efficacy and Safety of Three Cycles of TIP and Sequential High Dose Chemotherapy in Patients with Testicular Non-Seminomatous Germ Cell Tumors

<b>Background</b>: Salvage treatment options have not been validated in relapsed or refractory germ cell tumors. Moreover, the study populations including these patients have different heterogeneities. This study aimed to evaluate the efficacy and safety of three cycles of TIP sequential high-dose chemotherapy in patients with testicular non-seminomatous germ cell tumors who relapsed or had a refractory course after first-line platinum-based chemotherapy. <b>Methods</b>: Data of 141 patients who underwent three cycles of TIP followed by HDCT due to relapsed/refractory gonadal NSGCTs after first-line cisplatin-based chemotherapy (BEP/EP) at Gulhane School of Medicine Hospital Medical Oncology Department between January 2017 and May 2024 were evaluated retrospectively. Patients underwent a treatment regimen consisting of two phases. Initially, they received three cycles of induction therapy using a combination known as TIP, which includes paclitaxel, ifosfomide, and cisplatin. Following this, they were given a single cycle of high-dose chemotherapy. Demographic and clinicopathological features of patients and treatment-related complications and survival outcomes were recorded. <b>Results</b>: Median follow-up for all patients was 35.2 (95% CI, 29.45 to 41.07) months. Complete Response (CR) or marker negative Partial Response (PR) after HDCT was achieved in 84 (59.6%) patients. Median time for PFS not reached (NR) (95% CI, NR) in the entire group. The 2-year PFS rate was 51.8%. Median time for OS not reached (95% CI, NR) and the 2-year OS rate was 72.3%. The most common myelotoxicity observed after HDCT until engraftment was grade 4 neutropenia (100%) and grade 4 thrombocytopenia (96.5%). Transplantation-related mortality occurred in 7.1% of patients. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis for overall survival were platinum refractory disease and AFP and/or beta HCG elevation. <b>Conclusions</b>: Significant survival can be achieved after three cycles of TIP consecutive HDCT, while treatment-related mortality was found to be low.