Faivre S, Le Chevalier T, Monnerat C, Lokiec F, Novello S, Taieb J, Pautier P, Lhommé C, Ruffié P, Kayitalire L, Armand J-P, Raymond E
Department of Medicine, Institut Gustave-Roussy, Villejuif, France.
Ann Oncol. 2002 Sep;13(9):1479-89. doi: 10.1093/annonc/mdf219.
The aim of this study was to determine the toxicity profile, the recommended dose (RD) and the pharmacokinetic parameters, and to evaluate the antitumor activity of gemcitabine combined with oxaliplatin in patients with advanced non-small-cell lung cancer (NSCLC) and ovarian carcinoma (OC).
Gemcitabine was administered as a 30-min infusion followed by a 2-h infusion of oxaliplatin, repeated every 2 weeks. Doses of gemcitabine and oxaliplatin ranged from 800 to 1500 and 70 to 100 mg/m(2), respectively.
Forty-four patients (26 males, 18 females; median age 55 years) including 35 NSCLC (five platinum pretreated) and nine OC patients (all platinum pretreated) received a total of 355 cycles. All patients were evaluable for toxicity. No dose-limiting toxicity at any dose level occurred during the first two cycles; therefore, the highest dose-level of gemcitabine (1500 mg/m(2)) and oxaliplatin (85 mg/m(2)) was considered as the RD. Hematological toxicity was moderate amongst the 22 patients treated (167 cycles) at that dose level. Thirteen cycles were associated with grade 3-4 non-febrile neutropenia in six patients, and eight cycles with grade 3-4 thrombocytopenia in two patients. Other toxicities were mild to moderate, consisting of asthenia and peripheral neurotoxicity. Four of the 35 patients treated with oxaliplatin 85 mg/m(2) experienced grade 3 neurotoxicity requiring treatment discontinuation at cycle 10. In the range of the doses used, gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine appeared not to be affected by oxaliplatin 70-100 mg/m(2). Of the 44 patients evaluable for activity, 12 NSCLC patients experienced objective responses (one complete and 11 partial responses) and three OC patients showed tumor stabilization lasting for 6 months with a 50% decrease of CA 125 level. Two partial responses (NSCLC) and one tumor stabilization (OC) occurred in platinum-resistant patients.
The combination of gemcitabine and oxaliplatin could be safely administered on an out-patient schedule in patients with advanced NSCLC and OC. The RD was gemcitabine 1500 mg/m(2) and oxaliplatin 85 mg/m(2) every 2 weeks. Promising antitumor activity was reported in patients with NSCLC and platinum-pretreated OC, and thus, deserves further evaluation.
本研究旨在确定吉西他滨联合奥沙利铂在晚期非小细胞肺癌（NSCLC）和卵巢癌（OC）患者中的毒性特征、推荐剂量（RD）和药代动力学参数，并评估其抗肿瘤活性。
吉西他滨静脉输注30分钟，随后奥沙利铂静脉输注2小时，每2周重复一次。吉西他滨和奥沙利铂的剂量分别为800至1500mg/m²和70至100mg/m²。
44例患者（26例男性，18例女性；中位年龄55岁），包括35例NSCLC患者（5例曾接受铂类治疗）和9例OC患者（均曾接受铂类治疗），共接受了355个周期的治疗。所有患者均可进行毒性评估。在前两个周期中，任何剂量水平均未出现剂量限制性毒性；因此，吉西他滨（1500mg/m²）和奥沙利铂（85mg/m²）的最高剂量水平被视为RD。在该剂量水平接受治疗的22例患者（167个周期）中，血液学毒性为中度。13个周期出现3-4级非发热性中性粒细胞减少，发生在6例患者中；8个周期出现3-4级血小板减少，发生在2例患者中。其他毒性为轻度至中度，包括乏力和外周神经毒性。接受85mg/m²奥沙利铂治疗的35例患者中有4例在第10周期出现3级神经毒性，需要停药。在所使用的剂量范围内，吉西他滨及其主要代谢产物2',2'-二氟脱氧尿苷似乎不受70-100mg/m²奥沙利铂的影响。在44例可评估活性的患者中，12例NSCLC患者出现客观缓解（1例完全缓解和11例部分缓解），3例OC患者肿瘤稳定持续6个月，CA 125水平下降50%。铂耐药患者中出现2例部分缓解（NSCLC）和1例肿瘤稳定（OC）。
吉西他滨和奥沙利铂联合方案可在门诊安全地用于晚期NSCLC和OC患者。RD为吉西他滨1500mg/m²和奥沙利铂85mg/m²，每2周一次。在NSCLC和曾接受铂类治疗的OC患者中报告了有前景的抗肿瘤活性，因此值得进一步评估。
