Chollet P, Bensmaïne M A, Brienza S, Deloche C, Curé H, Caillet H, Cvitkovic E
Centre Jean Perrin, Clermont-Ferrand, France.
Ann Oncol. 1996 Dec;7(10):1065-70. doi: 10.1093/oxfordjournals.annonc.a010500.
Platinum-containing chemotherapy combinations achieve high response rates in women with advanced ovarian cancer. Unfortunately, most patients need further therapeutic options. Oxaliplatin (L-OHP) is a diaminocyclohexane (DACH) platinum analog active against human and murine cells in vitro and in vivo, including ovarian cells lines, with non-cross resistance characteristics with first (CDDP) and second (CBDCA) generation platinum compounds. The single agent activity of oxaliplatin in 34 consecutive platinum-pretreated ovarian cancer patients, not eligible for other phase II trials, was explored in a compassionate use program framework in a single institution.
Thirty-five patients (34 of them eligible) were treated by L-OHP at the median initial dose of 100 mg/sqm q 3 weeks (5 patients: 58-89 mg/m2; 24 patients: 90-100 mg/m2; 6 patients: 120-130 mg/m2) by short (30'-2 hours) i.v. infusion; the treatment was repeated every three weeks until treatment limiting toxicity or disease progression.
Thirty-one patients (median previous chemotherapy lines: 3) were evaluable for antitumoral activity, with a 29% objective response rate. According to Markman's criteria, objective partial responses were seen in six out of 13 evaluable potentially platinum-sensitive patients (46%) and three responses in the 18 evaluable platinum-resistant patients (17%). The tolerance was excellent, with no grade 3-4 (WHO) leukoneutropenia despite previous ABMT and abdominopelvic radiotherapy in six and eight cases, respectively. There was no renal or ototoxicity, and nausea/vomiting were moderate. The only grade 3 (WHO) peripheral neuropathy recorded concerned a patient with a neurotoxicity status grade 2 at baseline.
The 29% ORR single agent activity of oxaliplatin at hematological subtoxic doses in heavily pretreated ovarian cancer patients, with objective responses in platinum refractory patients, supports experimental data on non cross-resistance and a differential clinical toxicity profile to other available platinum compounds. The 12 month median overall survival of this poor prognosis patients cohort (62% platinum-refractory patients, median number of three previous chemotherapy lines) gives a strong empirical basis for the further exploration of oxaliplatin's role in confirmatory phase II and combination chemotherapy studies.
含铂化疗方案在晚期卵巢癌女性患者中可获得较高的缓解率。不幸的是，大多数患者需要进一步的治疗选择。奥沙利铂（L-OHP）是一种二氨基环己烷（DACH）铂类似物，在体外和体内对人和鼠细胞均有活性，包括卵巢细胞系，与第一代（顺铂，CDDP）和第二代（卡铂，CBDCA）铂化合物无交叉耐药特性。在一个单一机构的同情用药项目框架内，探讨了奥沙利铂对34例连续接受铂类预处理且不符合其他II期试验条件的卵巢癌患者的单药活性。
35例患者（其中34例符合条件）接受奥沙利铂治疗，初始中位剂量为100mg/m²，每3周一次（5例患者：58 - 89mg/m²；24例患者：90 - 100mg/m²；6例患者：120 - 130mg/m²），通过短时间（30分钟至2小时）静脉输注；每3周重复治疗，直至出现治疗限制毒性或疾病进展。
31例患者（既往化疗线数中位数：3）可评估抗肿瘤活性，客观缓解率为29%。根据马克曼标准，在13例可评估的潜在铂敏感患者中有6例出现客观部分缓解（46%），在18例可评估的铂耐药患者中有3例出现缓解（17%）。耐受性良好，尽管分别有6例和8例患者既往接受过自体骨髓移植和腹盆腔放疗，但未出现3 - 4级（WHO）白细胞减少。无肾毒性或耳毒性，恶心/呕吐为中度。唯一记录的3级（WHO）周围神经病变发生在一名基线时神经毒性状态为2级的患者身上。
奥沙利铂在血液学亚毒性剂量下对重度预处理的卵巢癌患者单药活性为29%的客观缓解率，在铂难治性患者中也有客观缓解，这支持了关于其与其他现有铂化合物无交叉耐药及不同临床毒性特征的实验数据。该预后不良患者队列（62%为铂难治性患者，既往化疗线数中位数为3）的中位总生存期为12个月，为进一步探索奥沙利铂在确证性II期和联合化疗研究中的作用提供了有力的经验依据。
