Frasci G, Comella G, Comella P, Conforti S, Mastrantonio P, Zullo F, Persico G
VII Division of General Surgery, University Federico II, Naples, Italy.
Gynecol Oncol. 1995 Jul;58(1):68-73. doi: 10.1006/gyno.1995.1185.
Hexamethylmelamine (HMM) and oral etoposide (VP-16) have shown to be active against platinum-resistant epithelial ovarian cancer. On this basis a three-drug regimen including carboplatin (CBDCA) plus HMM and oral VP-16 was tested in previously untreated ovarian cancer patients with tumor size > 2 cm. Since October 1991, 29 chemotherapy-naive ovarian cancer patients with tumor larger than 2 cm (20 stage III and 9 stage IV) have been treated for a total of 153 courses. CBDCA was administered i.v. on Day 1. The dose was individualized using the Calvert formula (the target dose was AUC = 5). VP-16 was administered orally at the dose of 50 mg/m2 Days 1-14, HMM at the dose of 150 mg/m2 po Days 14-28. Therapy was repeated every 28 days for a total of 6 courses. In order to avoid severe leukopenia and delays in the treatment administration, G-CSF 5 micrograms/kg/day sc Days 8-14 (or until postnadir recovery of neutrophil count > 10,000/mm3) and Days 22-28 was administered. All patients were evaluable for toxicity. No treatment-related deaths occurred. Myelotoxicity was the main side effect. It was grade 3-4 in a total of 13/29(45%) patients. One patient discontinued treatment after the first course due to HMM-related gastrointestinal toxicity. The actual delivered dose intensity was 89% of the planned dose. At the time of this analysis (April 1994) 26 patients are evaluable for response. Fifteen patients achieved a clinical complete remission and 9 a partial response for a 92% overall response rate. Fourteen patients accepted second-look laparotomy. We observed 11 pathological complete regressions (42%; 95% CI, 21-63). At a median follow-up of 16 months 3 deaths have occurred. Only 2 patients with NED at second-look laparotomy have relapsed. We stopped the accrual since the 95% confidence interval of the pCR-rate observed exceeded 20%. This new first-line regimen seems to be highly effective in patients with poor-prognosis advanced ovarian cancer, although the data are not yet sufficiently mature for a final analysis of time to progression and overall survival.
六甲蜜胺（HMM）和口服依托泊苷（VP - 16）已显示出对铂耐药的上皮性卵巢癌有活性。在此基础上，对29例既往未接受过治疗、肿瘤大小>2 cm的卵巢癌患者，测试了一种包含卡铂（CBDCA）加HMM和口服VP - 16的三联疗法。自1991年10月以来，29例初治的肿瘤大于2 cm的卵巢癌患者（20例为III期，9例为IV期）共接受了153个疗程的治疗。CBDCA于第1天静脉给药。剂量根据卡尔弗特公式个体化（目标剂量为AUC = 5）。VP - 16于第1 - 14天口服，剂量为50 mg/m²；HMM于第14 - 28天口服，剂量为150 mg/m²。治疗每28天重复一次，共6个疗程。为避免严重白细胞减少和治疗延迟，于第8 - 14天（或直至中性粒细胞计数最低点后恢复>10,000/mm³）及第22 - 28天皮下注射G - CSF 5微克/千克/天。所有患者均可评估毒性。未发生与治疗相关的死亡。骨髓毒性是主要副作用。共有13/29（45%）例患者为3 - 4级。1例患者在第一个疗程后因HMM相关的胃肠道毒性而停止治疗。实际给予的剂量强度为计划剂量的89%。在本次分析时（1994年4月），26例患者可评估疗效。15例患者达到临床完全缓解，9例部分缓解，总缓解率为92%。14例患者接受了二次剖腹探查。我们观察到11例病理完全缓解（42%；95%CI，21 - 63）。在中位随访16个月时，发生了3例死亡。二次剖腹探查时处于无疾病证据状态的患者中只有2例复发。由于观察到的病理完全缓解率的95%置信区间超过了20%，我们停止了入组。这种新的一线治疗方案似乎对预后不良的晚期卵巢癌患者非常有效，尽管数据尚未足够成熟以对进展时间和总生存期进行最终分析。
