Loehrer P J, Lauer R, Roth B J, Williams S D, Kalasinski L A, Einhorn L H
Indiana University School of Medicine, Indianapolis.
Ann Intern Med. 1988 Oct 1;109(7):540-6. doi: 10.7326/0003-4819-109-7-540.
To determine the efficacy of the addition of ifosfamide to cisplatin plus etoposide (VIP), or vinblastine (VeIP), in patients with recurrent germ cell tumors.
Nonrandomized, prospective phase II trial.
Tertiary referral university hospital.
Fifty-six of fifty-eight entered patients with measurable and progressive recurrent germ cell tumors of testicular (46 patients), ovarian (1 patient), and extragonadal (9 patients) origin were evaluable for response after not being cured with cisplatin, vinblastine, and etoposide regimens.
Patients were administered cisplatin (20 mg/m2 body surface area daily for 5 days), ifosfamide (1.2 g daily for 5 days), plus either etoposide (75 mg daily for 5 days) or vinblastine (0.11 mg/kg body weight on days 1 and 2). In addition, vigorous intravenous hydration therapy with normal saline (100 to 125 mL/h) was administered during the treatment course. Uroepithelial protective agents, N-acetylcysteine (orally) or mesna (intravenously), were administered. Four courses were administered to responding patients every 3 weeks. When complete excision was feasible, surgical resection of residual tumor was done approximately 6 to 8 weeks after chemotherapy.
Twelve of fifty-six evaluable patients had a complete remission with chemotherapy alone, whereas 8 additional patients were free of disease after resection of teratoma (3 patients) or carcinoma (5 patients) for a total disease-free rate of 36% (95% CI, 23.4 to 49.6). The 95% CI median duration of remission for these patients is 34 months (range, 3 to more than 42; 95% CI, 9 months to infinity), and the median survival for all eligible patients is 12.7 months (95% CI, 10 months to 26 months), with 15 of the 20 patients who achieved disease-free status alive 18 to 53 months or more. Nine of fifty-eight patients remain free of disease, including 7 patients for 2 years or longer. Hematologic and nephrotoxicity were the predominant drug-related toxicities, with one drug-related death secondary to pneumonia.
Ifosfamide combination chemotherapy as third-line or greater therapy can produce durable complete remissions in heavily pretreated patients with recurrent germ cell tumors.
确定在顺铂加依托泊苷（VIP）或长春花碱（VeIP）方案基础上加用异环磷酰胺对复发性生殖细胞肿瘤患者的疗效。
非随机前瞻性II期试验。
三级转诊大学医院。
58例入组患者中有56例患有可测量且进展性复发性生殖细胞肿瘤，起源于睾丸（46例）、卵巢（1例）和性腺外（9例），在接受顺铂、长春花碱和依托泊苷方案治疗未治愈后可评估反应。
患者接受顺铂（20mg/m²体表面积，每日1次，共5天）、异环磷酰胺（每日1.2g，共5天），加用依托泊苷（每日75mg，共5天）或长春花碱（第1天和第2天，0.11mg/kg体重）。此外，在治疗过程中给予大量生理盐水静脉水化治疗（100至125mL/h）。给予尿路上皮保护剂，N - 乙酰半胱氨酸（口服）或美司钠（静脉注射）。对有反应的患者每3周给予4个疗程。当可行完全切除时，化疗后约6至8周对残留肿瘤进行手术切除。
56例可评估患者中有12例仅通过化疗获得完全缓解，另外8例患者在切除畸胎瘤（3例）或癌（5例）后无疾病，总无病率为36%（95%CI，23.4至49.6）。这些患者95%CI的缓解持续时间中位数为34个月（范围，3至超过42；95%CI，9个月至无穷大），所有符合条件患者的中位生存期为12.7个月（95%CI，10个月至26个月），20例达到无病状态的患者中有15例存活18至53个月或更长时间。58例患者中有9例仍无疾病，包括7例持续2年或更长时间。血液学和肾毒性是主要的药物相关毒性，有1例与药物相关的死亡继发于肺炎。
异环磷酰胺联合化疗作为三线或更高级别的治疗可使经过大量预处理的复发性生殖细胞肿瘤患者产生持久的完全缓解。
