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Aims: This study aimed to evaluate the overall survival (OS) after the ifosfamide carboplatin plus etoposide (ICE) protocol for patients with relapsed refractory germ cell tumors (GCT). Differences in the contribution of the ICE protocol to patient survival according to the number of the treatment lines (four or more lines vs. three or fewer lines) were also evaluated. Methods: This retrospective cross-sectional study included patients with relapsed refractory GCT who had previously received multiple-line chemotherapy. Gender, age, clinical stage at diagnosis, tumor marker levels, visceral metastasis status, previous treatment protocols, response rates to ICE, follow-up time, and hematologic side effects were recorded. The primary endpoint was OS after the ICE. The secondary endpoint was the difference in OS between patients who received the ICE on the fourth and subsequent lines vs. those who received the third and previous lines. Results: The final sample included 15 patients (median age 26; males: 93.3%). At diagnosis, 80% of the patients had stage IIIC disease. The median OS in the whole group was 14.0 [interquartile range (IQR) 15.4] months. The median (IQR) OS after the ICE protocol in patients with three or fewer lines was significantly higher than in those who received four or more lines [21.6 (34.5) vs 10.8 (11.6), p=0.034]. Grade 3 neutropenia (46.6%), anemia (40%), and thrombocytopenia (40%) were frequently observed. Conclusions: For heavily pretreated relapsed/refractory GCT, the ICE may show the potential to provide a significant survival. However, more severe hematological side effects may be encountered. [ABSTRACT FROM AUTHOR]