Impact of bleomycin shortage on real-world outcomes in germ cell tumors: A multicenter retrospective analysis in Brazil.

Abstract

600 Background: Male germ cell tumors are rare malignancies, accounting for approximately 5% of all male cancers and predominantly affecting young adults. Most originate in the testis and are classified as seminomatous or non-seminomatous. Depending on clinical stage, different polychemotherapy regimens may be indicated, with or without bleomycin. Since 2017, Brazil—like several other countries—has faced recurrent shortages of bleomycin due to reduced global production, limited raw material availability, regulatory and logistical import barriers, and low commercial incentives for manufacturing this low-cost drug. In this context, this study aimed to evaluate the clinical impact of bleomycin unavailability on treatment outcomes in patients with germ cell tumors. Methods: A retrospective study was conducted including patients with germ cell tumors treated from 2017 to 2024 in two large public oncology centers in Brazil. Outcomes were compared between patients receiving bleomycin-containing regimens (BEP: bleomycin, etoposide, and cisplatin) and alternative regimens without bleomycin (EP: etoposide and cisplatin; VIP: etoposide, ifosfamide, and cisplatin). Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method, and factors associated with treatment type were evaluated through multivariate logistic regression. Additionally, hospitalization rates, treatment delays, and chemotherapy-related toxicities were assessed and compared between groups. Results: A total of 179 patients with germ cell tumors were evaluated. Among them, 57 received BEP, 36 received EP, and 13 received VIP. The comparative analysis of survival and treatment outcomes was performed between the BEP group and the combined non-bleomycin group (EP/VIP). There was no statistically significant difference in OS (p=0.593) or DFS (p=0.480) in the comparison of these 2 groups. Hospitalization rates (40.8% vs. 31.6%; p=0.323) and overall toxicity profiles were similar. However, patients treated without bleomycin presented a higher frequency of non-infectious hematologic toxicities (25.9% vs. 14.3%), which may have contributed to the significantly higher rate of treatment delays (59.2% vs. 33.3%; p=0.008). These adverse events generally did not require hospitalization but led to temporary chemotherapy postponements to allow hematologic recovery. Conclusions: Replacing bleomycin with alternative regimens (EP/VIP) did not compromise survival outcomes and showed comparable hospitalization and overall toxicity rates, although a higher rate of treatment delays was observed, likely due to increased mild or moderate hematologic toxicities. These real-world data support the feasibility of non-bleomycin regimens in contexts of drug shortage and contribute to evidence-based clinical decisions in germ cell tumor management.