Mäenpää Johanna U, Grénman Seija E, Jalkanen Jyrki T, Kuoppala Tapio A, Leminen Arto O, Puistola Ulla S, Vuolo-Merilä Päivi M, Yliskoski Merja H
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University Hospital of Tampere, Tampere, Finland.
Gynecol Oncol. 2006 Apr;101(1):114-9. doi: 10.1016/j.ygyno.2005.09.043. Epub 2005 Nov 2.
To determine the feasibility and efficacy of sequential gemcitabine-carboplatin followed by paclitaxel-carboplatin in the first-line treatment of advanced epithelial ovarian cancer, with the response rate as the primary endpoint.
After primary laparotomy, 56 patients with FIGO Stages III-IV disease were given 4 cycles of gemcitabine 1000 mg/m2 d1,8 and carboplatin AUC5 (44 patients) or AUC6 (12 patients) d1 q3wk followed by 4 cycles of paclitaxel 175 mg/m2 d1 and carboplatin AUC5/6 q3wk. Of the tumors, 43 were serous, 6 clear cell, 4 endometrioid, and 3 anaplastic type. Thirty-seven (66.1%) of the patients were suboptimally debulked.
Forty-seven patients were evaluable for response by CA-125 criteria, and 46 (98%) responded. Thirty patients (after gemcitabine-carboplatin) and 24 (after paclitaxel-carboplatin) were evaluable for response by CT (RECIST criteria), respectively. After the four gemcitabine-carboplatin cycles, the objective response rate was 83% (6 CR, 19 PR). Following completion of the whole sequential regimen, 7 patients showed a CR and 15 a PR, respectively, giving a response rate of 92%. The median progression-free survival was 12.8 months after a median follow-up of 19 months (range 7-35 months). The median overall survival has not been reached yet. The main toxicity was neutropenia as 139/221 (62.9%) of the gemcitabine-carboplatin cycles and 92/181 (50.8%) of the paclitaxel-carboplatin cycles, respectively, were associated with Grades 3-4 neutropenia. Neutropenia was reported as a serious adverse event in 5.7% of the cycles, and G-CSF support was needed in 18.4% of the cycles. Only the gemcitabine-carboplatin cycles were associated with a marked thrombocytopenia (32.1% Grades 3-4). Of the other side effects, marked allergy occurred in 14/52 (27%) exposed to paclitaxel. A total of 14 patients discontinued the treatment prematurely: 3 due to lack of efficacy, 1 due to protocol violation, and 10 due to toxicity (4 allergic reactions to paclitaxel, 3 complicated neutropenias, 1 fever, and 2 unspecified toxicities). The mean relative dose intensities were: gemcitabine 84.0%, paclitaxel 85.4%, and carboplatin 96.5%. Of the gemcitabine-carboplatin cycles and paclitaxel-carboplatin cycles, 32% and 38% were delayed, respectively. Gemcitabine d8 dose had to be omitted in 8% of the cycles.
The sequential regimen of gemcitabine-carboplatin followed by paclitaxel-carboplatin is feasible in chemotherapy-naive ovarian cancer. Although its use is associated with a marked neutropenia, the neutropenia is manageable.
以缓解率为主要终点，确定吉西他滨 - 卡铂序贯紫杉醇 - 卡铂一线治疗晚期上皮性卵巢癌的可行性和疗效。
56例国际妇产科联盟（FIGO）III - IV期疾病患者在初次剖腹手术后，接受4个周期的吉西他滨1000mg/m²第1、8天，卡铂AUC5（44例患者）或AUC6（12例患者）第1天，每3周1次，随后接受4个周期的紫杉醇175mg/m²第1天，卡铂AUC5/6每3周1次。肿瘤类型中，浆液性43例，透明细胞6例，子宫内膜样4例，间变3例。37例（66.1%）患者肿瘤减灭术未达理想状态。
47例患者可根据CA - 125标准评估缓解情况，46例（98%）有反应。30例（吉西他滨 - 卡铂治疗后）和24例（紫杉醇 - 卡铂治疗后）可分别根据CT（RECIST标准）评估缓解情况。4个吉西他滨 - 卡铂周期后，客观缓解率为83%（6例完全缓解，19例部分缓解）。整个序贯方案完成后，分别有7例患者完全缓解，15例部分缓解，缓解率为92%。中位无进展生存期为12.8个月，中位随访19个月（范围7 - 35个月）。中位总生存期尚未达到。主要毒性为中性粒细胞减少，吉西他滨 - 卡铂周期的139/221（62.9%）和紫杉醇 - 卡铂周期的92/181（50.8%）与3 - 4级中性粒细胞减少相关。中性粒细胞减少在5.7%的周期中被报告为严重不良事件，18.4%的周期需要粒细胞集落刺激因子（G - CSF）支持。仅吉西他滨 - 卡铂周期与明显的血小板减少相关（3 - 4级为32.1%）。在其他副作用中，14/52（27%）接受紫杉醇治疗的患者出现明显过敏。共有14例患者提前终止治疗：3例因疗效不佳，1例因违反方案，10例因毒性（4例对紫杉醇过敏反应，3例复杂性中性粒细胞减少，1例发热，2例未明确的毒性）。平均相对剂量强度分别为：吉西他滨84.0%，紫杉醇85.4%，卡铂96.5%。吉西他滨 - 卡铂周期和紫杉醇 - 卡铂周期分别有32%和38%延迟。8%的周期不得不省略吉西他滨第8天的剂量。
吉西他滨 - 卡铂序贯紫杉醇 - 卡铂方案用于初治卵巢癌化疗是可行的。虽然其使用与明显的中性粒细胞减少相关，但中性粒细胞减少是可控的。
