Raspagliesi Francesco, Zanaboni Flavia, Vecchione Francesca, Hanozet Francesco, Scollo Paolo, Ditto Antonino, Grijuela Barbara, Fontanelli Rosanna, Solima Eugenio, Spatti Gianbattista, Scibilia Giuseppe, Kusamura Shigeki
Gynecologic Oncology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Oncology. 2004;67(5-6):376-81. doi: 10.1159/000082921.
The aim of this multicenter feasibility study was to determine the toxicity profile and antitumor activity of the gemcitabine plus oxaliplatin combination as second-line treatment in platinum plus paclitaxel resistant/refractory advanced ovarian cancer.
Twenty patients received a 30-60-min infusion of gemcitabine a week for 2 weeks, followed by 120-180 min infusion of oxaliplatin every 3 weeks. The doses used were 1,000 and 130 mg/m(2), respectively. Seventeen cases (85% of the total) were platinum resistant and 3 (15%) were platinum refractory.
Grade 3/4 thrombocytopenia occurred in 14/20 of cases (70%); there were no symptomatic cases. 2 patients required platelet transfusion and 8 patients received hydrocortisone. The dose- limiting toxicity was thrombocytopenia. Combined grade 3/4 neutropenia was observed in 8/20 (40%) of cases (no sepsis was registered). Five patients were treated with recombinant erythropoietin because of grade 3 anemia and 4 cases received G-CSF prophylactically from the first cycle. The overall response rate of the combination in terms of antitumor activity was 26% (95% CI = 9-51%).
A combination of gemcitabine and oxaliplatin using this schedule gave rise to a moderate/severe toxicity profile and would be feasible only if growth factors were used and/or gemcitabine were administered at lower doses. The antitumor activity of the combination was insufficient reward for the resultant toxicity profile. However, equivalent to that of other drugs used in platinum refractory and resistant patients.
本多中心可行性研究旨在确定吉西他滨联合奥沙利铂作为二线治疗方案，用于铂类联合紫杉醇耐药/难治的晚期卵巢癌的毒性特征和抗肿瘤活性。
20例患者接受吉西他滨每周1次、每次30 - 60分钟的静脉输注，共2周，随后每3周接受120 - 180分钟的奥沙利铂静脉输注。使用的剂量分别为1000mg/m²和130mg/m²。17例（占总数的85%）为铂类耐药，3例（15%）为铂类难治。
14/20例（70%）出现3/4级血小板减少；无有症状病例。2例患者需要输注血小板，8例患者接受氢化可的松治疗。剂量限制性毒性为血小板减少。8/20例（40%）观察到3/4级中性粒细胞减少合并症（未记录到败血症）。5例因3级贫血接受重组促红细胞生成素治疗，4例从第1周期开始预防性使用粒细胞集落刺激因子。联合用药的总体抗肿瘤活性缓解率为26%（95%CI = 9 - 51%）。
按照此方案使用吉西他滨和奥沙利铂联合治疗会产生中度/重度毒性特征，仅在使用生长因子和/或以较低剂量使用吉西他滨时才可行。联合用药的抗肿瘤活性不足以抵消由此产生的毒性特征。然而，与用于铂类难治和耐药患者的其他药物相当。
