Akerley Wallace, Herndon James E, Egorin Merrill J, Lyss Alan P, Kindler Hedy L, Savarese Dianne M, Sherman Carol A, Rosen D Marc, Hollis Donna, Ratain Mark J, Green Mark R
Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84103, USA.
Cancer. 2003 May 15;97(10):2480-6. doi: 10.1002/cncr.11375.
The Cancer and Leukemia Group B conducted a Phase II trial to evaluate the efficacy, toxicity, and pharmacokinetics of paclitaxel administered at a maximum dose density for patients with chemotherapy-naïve, advanced-stage non-small cell lung carcinoma (NSCLC).
Patients with Stage IIIB/IV or recurrent NSCLC, a performance status (PS) score of 0-1, and no history of chemotherapy exposure were eligible. Paclitaxel, 150 mg/m(2), was administered over 3 hours during Weeks 1-6 of an 8-week cycle. Doses were modified for ANC < 1500/microL or for >or= Grade 2 neuropathy on the day of therapy. Treatment continued until toxicity or disease progression. Pharmacokinetics were assessed at Weeks 1, 3, and 5 of Cycle 1.
Thirty-eight patients (median age, 64 years; range, 31-81 years) were treated. There were 21 males (PS = 0 for 17). Eleven patients had received previous radiation, 2 had brain metastases, 25 had adenocarcinoma, 23 had Stage IV disease, 6 had StageIIIB disease, and 9 had recurrent disease. Grade 3-4 granulocytopenia occurred in 39% of patients. There were no deaths due to toxicity. Grade 2 or 3 neuropathy occurred in 29% and 24% of patients, respectively. Ten (27%) patients had Grade 3 hyperglycemia (glucose concentration > 250 mg/dL). There were 16 partial responses (42%; 95% confidence interval [CI], 26-59%). The median survival period was 12.3 months (95% CI, 7.9-19.6%), and the 1-year and 2-year survival rates were 52% (95% CI, 39-71%) and 26% (95% CI, 15-45%), respectively. Paclitaxel pharmacokinetics were consistent with published values and clearance was not induced. Older age and hyperglycemia were associated with greater neurotoxicity.
Paclitaxel at 150 mg/m(2) per week x 6 every 8 weeks can be administered safely in the cooperative group setting. These Phase II data are comparable to those associated with combination therapy. The weekly dose-dense schedule may be more active than conventional schedules.
癌症与白血病B组开展了一项II期试验，以评估对于未经化疗的晚期非小细胞肺癌（NSCLC）患者，给予最大剂量密度紫杉醇的疗效、毒性及药代动力学情况。
符合条件的患者为IIIB/IV期或复发性NSCLC患者，其体能状态（PS）评分为0 - 1，且无化疗史。在为期8周的周期中，第1 - 6周给予150 mg/m²的紫杉醇，静脉滴注3小时。若治疗当天中性粒细胞计数（ANC）< 1500/μL或出现≥2级神经病变，则调整剂量。治疗持续至出现毒性反应或疾病进展。在第1周期的第1、3和5周评估药代动力学。
共治疗38例患者（中位年龄64岁；范围31 - 81岁）。其中男性21例（17例PS = 0）。11例患者曾接受过放疗，2例有脑转移，25例为腺癌，23例为IV期疾病，6例为IIIB期疾病，9例为复发性疾病。39%的患者出现3 - 4级粒细胞减少。无毒性相关死亡病例。29%和24%的患者分别出现2级或3级神经病变。10例（27%）患者出现3级高血糖（血糖浓度> 250 mg/dL）。有16例部分缓解（42%；95%置信区间[CI]，26 - 59%）。中位生存期为12.3个月（95% CI，7.9 - 19.6%），1年和2年生存率分别为52%（95% CI，39 - 71%）和26%（95% CI，15 - 45%）。紫杉醇药代动力学与已发表值一致，且清除率未被诱导。年龄较大和高血糖与更严重的神经毒性相关。
每8周每周150 mg/m²×6的紫杉醇给药方案在协作组环境中可安全给药。这些II期数据与联合治疗相关数据相当。每周剂量密集方案可能比传统方案更有效。
