Gajra A, Mehdi S A, Kirshner J, Newman N, Graziano S L
State University of New York, Upstate Medical University, 750 E Adams Street, Syracuse, NY 13210, USA.
Lung Cancer. 2001 May;32(2):189-96. doi: 10.1016/s0169-5002(00)00213-0.
This phase I study was designed to determine the maximum tolerated dose of carboplatin with a fixed dose of gemcitabine without growth factor or hematopoietic precursor support.
Nineteen patients with previously untreated non-small cell lung cancer (NSCLC) were treated at three dose levels. Initially, the gemcitabine dose was 1000 mg/m(2) given on days 1 and 8. Of the first five patients treated with carboplatin AUC 4, three experienced dose limiting toxicity (DLT). The study was, therefore, amended to decrease the dose of gemcitabine to 800 mg/m(2) given on days 1 and 8 in a 21-day cycle.
Dose limiting toxicity (neutropenia and thrombocytopenia) were seen at dose level 2A (carboplatin AUC=5). Thus, no further dose escalation was performed. Grade 3 and 4 toxicities were seen as follows: leukopenia in five of 18 (28%); neutropenia, four of 18 (22%); and thrombocytopenia, four of 18 (22%) evaluable patients. Grade 3 or 4 anemia occurred in one of 18 (6%) patients and no neutropenic fever or treatment related mortality was observed. Partial responses were seen in six patients and one patient with evaluable disease had an objective response. The overall response rate was 37% (seven of 19). Six other patients had stable disease. A total of 89 courses were administered with a median of five courses per patient (range: two to six courses). The median time to progression for all patients was 3.7 months. The median overall survival was 7.4 months with four patients still alive (median follow up 13.5 months). The survival at 6 months and 1 year is 64 and 23%, respectively.
The maximum tolerated dose (MTD) in this group of patients was defined as carboplatin AUC 4 when administered with gemcitabine 800 mg/m(2) on days 1 and 8 of a 21-day schedule.
本I期研究旨在确定在不使用生长因子或造血前体细胞支持的情况下，与固定剂量吉西他滨联合使用时卡铂的最大耐受剂量。
19例既往未接受过治疗的非小细胞肺癌（NSCLC）患者接受了三个剂量水平的治疗。最初，吉西他滨剂量为1000mg/m²，于第1天和第8天给药。在最初接受卡铂AUC 4治疗的5例患者中，3例出现剂量限制性毒性（DLT）。因此，研究进行了修正，将吉西他滨剂量降至800mg/m²，在21天周期的第1天和第8天给药。
在剂量水平2A（卡铂AUC = 5）时观察到剂量限制性毒性（中性粒细胞减少和血小板减少）。因此，未进一步提高剂量。观察到的3级和4级毒性如下：18例可评估患者中有5例（28%）出现白细胞减少；18例中有4例（22%）出现中性粒细胞减少；18例中有4例（22%）出现血小板减少。18例患者中有1例（6%）出现3级或4级贫血，未观察到中性粒细胞减少性发热或治疗相关死亡。6例患者出现部分缓解，1例可评估疾病的患者有客观缓解。总缓解率为37%（19例中的7例）。另外6例患者病情稳定。共给予89个疗程，每位患者的中位数为5个疗程（范围：2至6个疗程）。所有患者的中位疾病进展时间为3.7个月。中位总生存期为7.4个月，4例患者仍存活（中位随访13.5个月）。6个月和1年时的生存率分别为64%和23%。
在这组患者中，最大耐受剂量（MTD）定义为在21天疗程的第1天和第8天与800mg/m²吉西他滨联合使用时卡铂的AUC 4。
