Guastalla J P, Lhomme C, Kerbrat P, Mayer F, Namer M, Goupil P, Charrot P, Heron J F, Chazard M, Richard I
Centre Léon Bérard, Lyon, France.
Ann Oncol. 1994 Feb;5(2):127-32. doi: 10.1093/oxfordjournals.annonc.a058763.
Because of its antitumour activity and its pharmacological advantage when administered by the intraperitoneal route, carboplatin was studied in a phase II multicentric trial. The aim of the study was to determine the response rate and the toxicity of carboplatin administered intraperitoneally and to determine if pathological complete response could be attained in women with macroscopic residual ovarian cancer at second-look laparotomy after intravenous cisplatin chemotherapy.
Twenty-nine patients with macroscopical residual disease after intravenous cisplatin-based chemotherapy at second-look laparotomy, were treated at that time with 300 mg/m2 of carboplatin administered in the abdominal cavity every four weeks for six cycles. In instances of negative findings at physical and CT scan examination, laparotomy evaluation was performed and the catheter was removed. The dose of carboplatin was increased or decreased according to hematological toxicity.
Efficacy is evaluable in 25 pts: 2 pts had pathological complete responses and 1 pt had microscopic disease (12% response rate of evaluable patients). Toxicity is evaluable for 135 cycles in 29 patients. No grade 4 hematological toxicity was observed, 2 pts had grade 3 leukopenia and 3 pts had grade 3 thrombocytopenia; grade 3 vomiting was observed in 11% of cycles. No peritoneal complication was observed; catheter dysfunction occurred after the first cycle in one patient who refused a surgical procedure to remove the catheter and to pursue treatment.
Intraperitoneal carboplatin demonstrates efficacy in patients with macroscopical residual disease at second-look laparotomy after first-line cisplatin chemotherapy. The recommended dose for further studies is 300 mg/m2 administered every 4 weeks. A low response rate does not favour a randomised study.
由于卡铂具有抗肿瘤活性以及经腹腔给药时的药理学优势，因此开展了一项II期多中心试验对其进行研究。该研究的目的是确定腹腔内给予卡铂的缓解率和毒性，并确定在静脉顺铂化疗后二次剖腹探查时存在肉眼可见残留卵巢癌的女性患者是否能达到病理完全缓解。
29例在二次剖腹探查时经基于顺铂的静脉化疗后有肉眼可见残留病灶的患者，在此时接受每四周一次、剂量为300mg/m²的卡铂腹腔给药，共六个周期。在体格检查和CT扫描检查结果为阴性的情况下，进行剖腹探查评估并拔除导管。根据血液学毒性增加或减少卡铂剂量。
25例患者的疗效可评估：2例患者达到病理完全缓解，1例患者有微小病灶（可评估患者的缓解率为12%）。29例患者的135个周期的毒性可评估。未观察到4级血液学毒性，2例患者出现3级白细胞减少，3例患者出现3级血小板减少；11%的周期观察到3级呕吐。未观察到腹膜并发症；1例患者在第一个周期后出现导管功能障碍，该患者拒绝接受手术拔除导管并继续治疗。
对于一线顺铂化疗后二次剖腹探查时有肉眼可见残留病灶的患者，腹腔内给予卡铂显示出疗效。进一步研究的推荐剂量为每4周给予300mg/m²。低缓解率不利于进行随机研究。
