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

Abstract

Our objective was to investigate the impact of methotrexate, paclitaxel, ifosfamide, and cisplatin (M-TIP) on longterm 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/m 2 with folinic acid rescue (day 1) and paclitaxel 175 mg/ m 2 (day 1), followed by ifosfamide 1.2 g/m 2 and cisplatin 20 mg/m 2 (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 6 10 6 /mL, azoospermia; 1-20 6 10 6 / mL, oligospermia (OS); higher than 20 6 10 6 /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. J Androl 2009;30:280-286T he treatment of metastatic germ cell tumors (GCT) with the introduction of cisplatin-based chemotherapy results in the cure of approximately 80% of patients (Bosl and Motzer, 1997). In 1997, the International Germ Cell Cancer Collaborative Group (IGCCCG) (1997) published a new classification system based on data collected from more than 5000 GCT patients treated from 1975 to 1990. This system classifies patients with disseminated GCT into good-, intermediate-, or poor-risk groups on the basis of 3 criteria: the primary tumor site, the levels of serum tumor markers, and whether nonpulmonary visceral metastases are present. According to this classification system, patients allocated to the good-risk group have a 5-year survival rate of 92%, whereas patients in the intermediate-and poor-risk groups have 5-year survival rates of 82% and 48%, respectively. Patients with markedly elevated tumor markers, nonpulmonary viscer...

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Anticancer Activity of a Combination of Cisplatin and Fisetin in Embryonal Carcinoma Cells and Xenograft Tumors

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