Hainsworth J D, Burris H A, Billings F T, Bradof J E, Baker M, Greco F A
Sarah Cannon Cancer Center, 250 25th Avenue North, Nashville, TN 37203, USA.
Cancer. 2001 Nov 1;92(9):2391-8. doi: 10.1002/1097-0142(20011101)92:9<2391::aid-cncr1587>3.0.co;2-m.
The current study was conducted to evaluate the feasibility, toxicity, and efficacy of weekly docetaxel when paired with either gemcitabine or vinorelbine as the second-line treatment of patients with advanced nonsmall cell lung carcinoma.
Patients with progressive nonsmall cell lung carcinoma after one previous chemotherapeutic regimen, an Eastern Cooperative Oncology Group performance status of 0-2, and measurable lesions were eligible for treatment in these Phase II trials. Patients who had not received gemcitabine previously were treated with docetaxel, 30 mg/m(2), and gemcitabine, 800 mg/m(2), both of which were administered intravenously (i.v.) on Days 1, 8, and 15 of a 28-day cycle. If the patients had received gemcitabine as part of first-line therapy, they were treated with docetaxel, 30 mg/m(2), and vinorelbine, 20 mg/m(2) i.v., on Days 1, 8, and 15 of a 28-day cycle. Patients were reevaluated after two courses of treatment, and responding patients continued treatment for six courses or until disease progression.
Forty patients were treated with a combination of docetaxel and gemcitabine, and 23 patients received docetaxel and vinorelbine. The docetaxel/gemcitabine combination was reasonably well tolerated, with moderate myelosuppression and a few nonhematologic toxicities reported. The objective response rate was 10%, with a 1-year survival rate of 20%. The docetaxel/vinorelbine combination was found to be poorly tolerated, with Grade 3/4 leukopenia reported in 71% of patients and neutropenic fever reported in 70% of patients despite frequent dose reductions and omission of the Day 15 doses. Enrollment onto this regimen was stopped prematurely due to toxicity, and after no major responses were observed in the first 20 evaluable patients.
The combination of weekly docetaxel/gemcitabine appears to be feasible and relatively well tolerated as second-line treatment in patients with advanced nonsmall cell lung carcinoma, whereas a weekly combination of docetaxel and vinorelbine did not appear to be tolerable at the doses and schedule used in the current study. Neither regimen showed a level of activity that suggested any advantage compared with the results obtained with single-agent docetaxel in this setting.
本研究旨在评估每周使用多西他赛联合吉西他滨或长春瑞滨作为晚期非小细胞肺癌患者二线治疗的可行性、毒性和疗效。
既往接受过一种化疗方案后病情进展、东部肿瘤协作组体能状态为0 - 2且有可测量病灶的非小细胞肺癌患者符合这些II期试验的治疗条件。既往未接受过吉西他滨治疗的患者接受多西他赛30mg/m²和吉西他滨800mg/m²治疗，二者均在28天周期的第1、8和15天静脉注射。如果患者在一线治疗中接受过吉西他滨治疗，则在28天周期的第1、8和15天接受多西他赛30mg/m²和长春瑞滨20mg/m²静脉注射治疗。患者在两个疗程治疗后重新评估，有反应的患者继续治疗六个疗程或直至疾病进展。
40例患者接受多西他赛与吉西他滨联合治疗，23例患者接受多西他赛与长春瑞滨联合治疗。多西他赛/吉西他滨联合方案耐受性较好，报告有中度骨髓抑制和一些非血液学毒性。客观缓解率为10%，1年生存率为20%。发现多西他赛/长春瑞滨联合方案耐受性差，尽管频繁降低剂量并省略第15天的剂量，但仍有71%的患者报告有3/4级白细胞减少，70%的患者报告有中性粒细胞减少性发热。由于毒性，该方案的入组提前终止，且在前20例可评估患者中未观察到主要反应。
每周使用多西他赛/吉西他滨联合方案作为晚期非小细胞肺癌患者的二线治疗似乎可行且耐受性相对较好，而在本研究使用的剂量和给药方案下，每周使用多西他赛和长春瑞滨联合方案似乎不可耐受。在这种情况下，两种方案均未显示出比单药多西他赛的结果有任何优势的活性水平。
