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Testicular Function in Poor-Risk Nonseminomatous Germ Cell Tumors Treated With Methotrexate, Paclitaxel, Ifosfamide, and Cisplatin Combination Chemotherapy

A. MACHERAS

From the ^* Second Department of Internal Medicine, Propaedeutic, Oncology Section; and the Third Department of Surgery, University of Athens, Attikon University Hospital, Haidari, Athens, Greece

Correspondence to: Dr D. Pectasides, Second Department of Internal Medicine, Propaedeutic, Oncology Section, Attikon University Hospital, Rimini 1, Haidari, Athens, Greece (e-mail: pectasid{at}otenet.gr).

Our objective was to investigate the impact of methotrexate, paclitaxel, ifosfamide, and cisplatin (M-TIP) on long-term fertility in poor-risk nonseminomatous germ cell tumors (NSGCT). Thirty patients with poor-risk NSGCT (median age, 29 years; range, 17–62 years) were treated with methotrexate 250 mg/m² with folinic acid rescue (day 1) and paclitaxel 175 mg/m² (day 1), followed by ifosfamide 1.2 g/m² and cisplatin 20 mg/m² (days 2–6). Treatment consisted of 4 cycles of M-TIP administered every 3 weeks. Twenty-one patients were continuously disease-free at a median follow-up of 5.3 years (range, 0.9–8.4 years). Sperm count and hormonal analyses were examined prechemotherapy (30 patients) and postchemotherapy (21 patients). Counts were classified as follows: lower than 1 x 10⁶/mL, azoospermia; 1–20 x 10⁶/mL, oligospermia (OS); higher than 20 x 10⁶/mL, normospermia (NS). Patients were followed for a median of 2.3 years (range, 0.9–3.8 years) postchemotherapy. The prechemotherapy median luteinizing hormone (LH) serum levels were slightly above the upper normal limit, whereas the serum levels of follicle-stimulating hormone (FSH) and testosterone (T) were within the reference interval. Eleven (52.3%) patients had NS prechemotherapy. Among the patients with NS, 72.7% still had NS following chemotherapy. Overall, 17 of 21 (80.9%; 33.3% OS and 47.6% NS) patients had recovery of spermatogenesis after treatment. The median FSH serum levels were significantly elevated at least 1 year postchemotherapy when compared with the pretreatment levels. Eighteen months after the completion of chemotherapy the median FSH levels had returned to the reference limits. Serum LH and T levels were unaffected by chemotherapy. Prior to chemotherapy 4 of 30 patients had fathered 5 children. Since completion of chemotherapy, 5 patients have fathered 5 children. The majority of men with poor-risk germ cell tumors who were treated with the M-TIP regimen demonstrated recovery spermatogenesis after treatment, and Leydig cell function was unaffected.

     Key words: Fertility, gonadal toxicity