Murad André M
Oncology Department, Hospital das Clínicas Universidade Federal de Minas Gerais Belo Horizonte, Brazil.
Oncology (Williston Park). 2003 Dec;17(12 Suppl 14):26-32.
Both paclitaxel and gemcitabine (Gemzar) have shown activity and manageable toxicity when used as single agents in heavily pretreated patients with metastatic breast cancer. This phase II study evaluated their use in combination for metastatic breast cancer patients whose disease recurred or progressed following treatment with anthracycline-containing regimens. Twenty-nine patients ranging from 32 to 68 years of age received paclitaxel at 175 mg/m2 i.v. over 3 hours on day 1 and gemcitabine at 1,000 mg/m2 i.v. on days 1, 8, and 15 every 28 days. Because of unacceptable thrombocytopenia in the first five patients, the gemcitabine schedule was changed to days 1 and 8 of a 21-day cycle for the remainder of the study. All 29 patients were evaluable for response and toxicity. Seventeen patients (59%) were considered truly anthracycline- or anthracenedione-refractory. A total of 137 cycles (median: 4 per patient) were administered. The regimen was well tolerated. Grade 3/4 thrombocytopenia was observed in 5 (18.5%) of the first 27 cycles and in 6 (5.4%) of the 110 cycles following dosage reduction (P = .04). Five patients had grade 1 and two patients had grade 3 neuropathy. Eight patients had grade 3 neutropenia, two had grade 4 neutropenia with fever at the higher dosage, and eight had grade 1/2 myalgia and fatigue. Five patients (17%) had a complete response and 11 (38%) a partial response, yielding an objective response rate of 55% (95% confidence interval = 36%-73%). Six patients (20.7%) had stable disease. Median response duration was 8 months (range: 4-26 months), and median overall survival was 12 months (range: 4-48+ months). Survival at 1, 2, 3, and 4 years was 45%, 30%, 20%, and 10%, respectively. The combination of paclitaxel on day 1 with gemcitabine on days 1 and 8 of a 21-day cycle appears to have promising activity in heavily pretreated patients with metastatic breast cancer. Phase III trials comparing this promising doublet to paclitaxel monotherapy and to other chemotherapeutic strategies for advanced breast cancer will clarify the role of this regimen.
紫杉醇和吉西他滨（健择）在用于治疗转移性乳腺癌的经大量预处理的患者时，均已显示出活性且毒性可控。这项II期研究评估了它们联合用于疾病在含蒽环类方案治疗后复发或进展的转移性乳腺癌患者的情况。29例年龄在32至68岁之间的患者在第1天接受静脉输注175mg/m²的紫杉醇，持续3小时，每28天的第1、8和15天接受静脉输注1000mg/m²的吉西他滨。由于前5例患者出现了不可接受的血小板减少症，在研究的剩余部分，吉西他滨的给药方案改为21天周期的第1天和第8天。所有29例患者均可评估疗效和毒性。17例患者（59%）被认为对蒽环类或蒽二酮类药物真正耐药。总共进行了137个周期（中位数：每位患者4个周期）。该方案耐受性良好。在前27个周期中有5例（18.5%）出现3/4级血小板减少症，在剂量降低后的110个周期中有6例（5.4%）出现（P = 0.04）。5例患者出现1级神经病变，2例患者出现3级神经病变。8例患者出现3级中性粒细胞减少症，2例在较高剂量时出现4级中性粒细胞减少症伴发热，8例出现1/2级肌痛和疲劳。5例患者（17%）完全缓解，11例（38%）部分缓解，客观缓解率为55%（95%置信区间 = 36%-73%）。6例患者（20.7%）病情稳定。中位缓解持续时间为8个月（范围：4 - 26个月），中位总生存期为12个月（范围：4 - 48 +个月）。1年、2年、3年和4年的生存率分别为45%、30%、20%和10%。在第1天给予紫杉醇与在21天周期的第1天和第8天给予吉西他滨的联合方案，在经大量预处理的转移性乳腺癌患者中似乎具有有前景的活性。将这种有前景的双联方案与紫杉醇单药治疗以及晚期乳腺癌的其他化疗策略进行比较的III期试验，将阐明该方案的作用。
