Piccart M J, Nogaret J M, Marcelis L, Longrée H, Ries F, Kains J P, Gobert P, Domange A M, Sculier J P, Gompel C
Service de Médecine, Institut Jules Border, Centre des Tumeurs de l'Université Libre de Bruxelles, Brussels, Belgium.
J Natl Cancer Inst. 1990 Apr 18;82(8):703-7. doi: 10.1093/jnci/82.8.703.
We performed a phase I-II trial of escalating doses of cisplatin (CDDP: 50-100 mg/m2 per course) plus carboplatin (CBDCA: 300-400 mg/m2 per course) as a potential way in which to maximize platinum doses without causing excessive toxic effects in patients with advanced ovarian cancer. Thirty-three patients with nonoptimally debulked disease of FIGO (International Federation of Gynecology and Obstetrics) stages IIc-IV [median age: 60 yr; median WHO (World Health Organization) performance status: 2; no prior chemotherapy] received a median of six courses of therapy. CBDCA was infused on day 1 and CDDP on day 2 with an aggressive 48-hour hydration regimen. Myelosuppression was dose-limiting: at the highest dose levels, WHO grade 4 neutropenia and thrombocytopenia led to dose reduction and/or treatment delay in 45% of the patients. Nonhematologic toxic effects included acute nausea and vomiting (97% of the patients), mild alopecia (45%), ototoxic effects (39%), neurotoxic effects (21%), and renal toxic effects (serum creatinine greater than 1.5 mg/dL: 12.5%). The pathologic complete response rate was 22%. We conclude that CBDCA and CDDP can be given safely in combination at reasonably high doses (CBDCA at 300 mg/m2 per course and CDDP at 100 mg/m2 per course) over a 6-month period, provided a close hematologic follow-up is conducted. Randomized clinical trials are needed to define whether this regimen is any better than standard combination chemotherapy.
我们进行了一项I-II期试验，采用逐步递增剂量的顺铂（CDDP：每疗程50 - 100 mg/m²）加卡铂（CBDCA：每疗程300 - 400 mg/m²），作为在晚期卵巢癌患者中使铂剂量最大化同时又不引起过度毒性作用的一种潜在方法。33例国际妇产科联盟（FIGO）IIc-IV期未达最佳减瘤效果的患者（中位年龄：60岁；中位世界卫生组织（WHO）体能状态：2；未接受过先前化疗）接受了中位6个疗程的治疗。CBDCA在第1天输注，CDDP在第2天输注，并采用积极的48小时水化方案。骨髓抑制是剂量限制性的：在最高剂量水平时，WHO 4级中性粒细胞减少和血小板减少导致45%的患者出现剂量减少和/或治疗延迟。非血液学毒性作用包括急性恶心和呕吐（97%的患者）、轻度脱发（45%）、耳毒性作用（39%）、神经毒性作用（21%）以及肾毒性作用（血清肌酐大于1.5 mg/dL：12.5%）。病理完全缓解率为22%。我们得出结论，在密切进行血液学随访的情况下，CBDCA和CDDP可以在6个月内以相当高的剂量（CBDCA每疗程300 mg/m²和CDDP每疗程100 mg/m²）安全联合使用。需要进行随机临床试验来确定该方案是否优于标准联合化疗。
