Soulié P, Raymond E, Brienza S, Cvitkovic E
Hôpital Paul-Brousse, Villejuif, France.
Bull Cancer. 1997 Jun;84(6):665-73.
Oxaliplatin is a new platinum analog of the DACH family. Recent preclinical data have confirmed its non overlapping spectrum of activity with cisplatin, including acquired and intrinsic platinum resistant cell lines (as KB-CP, A 2780, HT29, CaCo2 colon cancer). When combined with other cytotoxic agents (5FU, SN38, CDDP, carboplatin), oxaliplatin has additive and/or synergistic antitumoral effects on various in vitro and in vivo models (colon, breast, ovarian and epidermoid tumors). Phase II trials have confirmed a sensorial peripherical neuropathy as its limiting toxicity while neither ototoxicity nor renal toxicities and only limited myelotoxicity were noted. Available phase II studies have established its antitumoral activity as single agent in 5FU refractory colon carcinoma while preliminary results suggest efficacy in cisplatin resistant ovarian cancer, in non small cell lung cancer, non Hodgkin lymphoma. Antitumoral activity has been observed during phases 1 in melanoma, glioma, breast and oesophageal cancers. A high response rate (28-65%) with the triple association (FU/folinic acid/oxaliplatin) has been reported in advanced colon cancer treated in first and second line settings. The results of two randomized phase III studies (FU/folinic acid +/- oxaliplatin) are expected. The oxaliplatin/cisplatin combination as salvage regimen had produced significant antitumoral activity (response rate: 45%) in resistant/refractory ovarian cancer. Finally, recent experimental and clinical data have outlined the potential interest in the development of this new original platinum compound. New single agent phases II are expected in other tumor types as well as new oxaliplatin combinations are ongoing (phase I trials of oxaliplatin/CPT-11 and of oxaliplatin/carboplatin, phase II study of oxaliplatin-vinorelbine in lung cancer.
奥沙利铂是一种新型的二氨基环己烷类铂类似物。近期临床前数据已证实其与顺铂的活性谱不重叠，包括获得性和原发性铂耐药细胞系（如KB-CP、A2780、HT29、CaCo2结肠癌）。当与其他细胞毒性药物（5-氟尿嘧啶、SN38、顺铂、卡铂）联合使用时，奥沙利铂在各种体外和体内模型（结肠癌、乳腺癌、卵巢癌和表皮样肿瘤）中具有相加和/或协同抗肿瘤作用。II期试验已证实感觉性周围神经病变是其剂量限制性毒性，而未观察到耳毒性和肾毒性，仅观察到有限的骨髓毒性。现有的II期研究已证实其作为单药在5-氟尿嘧啶难治性结肠癌中具有抗肿瘤活性，而初步结果表明其在铂耐药卵巢癌、非小细胞肺癌、非霍奇金淋巴瘤中有效。在黑色素瘤、神经胶质瘤、乳腺癌和食管癌的I期研究中观察到了抗肿瘤活性。在一线和二线治疗的晚期结肠癌中，已报道三联方案（氟尿嘧啶/亚叶酸/奥沙利铂）具有较高的缓解率（28%-65%）。两项随机III期研究（氟尿嘧啶/亚叶酸±奥沙利铂）的结果值得期待。奥沙利铂/顺铂联合方案作为挽救方案在耐药/难治性卵巢癌中产生了显著的抗肿瘤活性（缓解率：45%）。最后，近期的实验和临床数据概述了开发这种新型原创铂化合物的潜在价值。预计在其他肿瘤类型中会开展新的单药II期研究，同时也在进行新的奥沙利铂联合方案（奥沙利铂/伊立替康和奥沙利铂/卡铂的I期试验，奥沙利铂/长春瑞滨在肺癌中的II期研究）。
