Wiernik P H, Yeap B, Vogl S E, Kaplan B H, Comis R L, Falkson G, Davis T E, Fazzini E, Cheuvart B, Horton J
Albert Einstein Cancer Center, Bronx, New York.
Cancer Invest. 1992;10(1):1-9. doi: 10.3109/07357909209032783.
A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (greater than 2- less than or equal to 10 cm, greater than 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less than or equal to 1 year, greater than 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age less than 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation.
共有248例可分析的III-IV期卵巢上皮癌患者（114例曾接受化疗，134例未接受过化疗）被随机分为四种顺铂（DDP）-六甲蜜胺（HMM）治疗方案中的一种。每种方案中，HMM剂量为200mg/m²，在每21天周期的第8 - 21天每日口服。DDP在第1天静脉注射，A组和B组剂量为37.5mg/m²，C组和D组剂量为75mg/m²。此外，由于已有报道称给予吡哆醇可降低HMM的神经毒性，在B组和D组中，该药物在第1 - 21天以300mg/m²的剂量口服。对于未接受过治疗的患者，随机分组按体能状态（0 - 1，2 - 3）和入组时最大肿瘤直径（大于2 - 小于或等于10cm，大于10cm）进行分层；对于曾接受过治疗的患者，则按体能状态以及从初次诊断到入组研究的时间（小于或等于1年，大于1年）进行分层。总缓解率（PR + CR）为54%，25%的患者达到完全缓解。高剂量DDP方案的缓解率为61%，显著高于低剂量方案的47%（p = 0.031）。多因素分析确定高DDP剂量、年龄小于60岁、未接受过化疗、肿瘤体积小和肿瘤分级良好是缓解的重要预后因素。总中位缓解持续时间为8.3个月（范围1 - 70个月）。多因素分析确定，曾接受化疗、给予吡哆醇、近期诊断和肿瘤体积大是影响缓解持续时间的不利因素。接受高剂量DDP方案治疗的患者恶心、呕吐和神经毒性更严重。本研究表明，DDP + HMM联合方案是晚期卵巢癌的有效治疗方案，缓解率与其他更复杂的方案相当，且卵巢癌中DDP存在剂量反应关系。虽然给予吡哆醇可显著降低神经毒性，但其对缓解持续时间的不利影响表明该药物不应与DDP或HMM联合使用。吡哆醇可能不利影响缓解持续时间的机制值得进一步研究。
