Murray N, Coppin C, Coldman A, Pater J, Rapp E
National Cancer Institute of Canada, Clinical Trials Group, Queen's University, Kingston.
J Clin Oncol. 1994 Nov;12(11):2333-9. doi: 10.1200/JCO.1994.12.11.2333.
The Canadian multicenter trial for advanced non-small-cell lung cancer (NSCLC) reported survival benefit for chemotherapy when best supportive care was compared with vindesine-cisplatin (VP) and the combination of cyclophosphamide, doxorubicin, and cisplatin (CAP). We examined received drug delivery to document dose-intensity (DI) and total dose of drugs given to various groups in this patient population.
Plots of cumulatively received chemotherapy against time were used to evaluate drug delivery by regimen, major prognostic factors, and response status.
Individual CAP patients show a narrow range of received DI, with the median similar to protocol. Drug delivery analysis exposed a wide range of received DI for both drugs in the more intensive VP regimen, and the median received DI was below protocol. The median received DI for cisplatin was still higher for VP than CAP, but only during the first 8 weeks of protocol treatment (20 v 10 mg/m2/wk); thereafter, the ongoing received cisplatin DI was the same (10 mg/m2/wk). The median received DI for cisplatin in each regimen was not influenced by stage, performance status, prior weight loss, sex, or response status. VP-treated patients received a higher total dose of cisplatin than CAP patients (median, 255 mg/m2 v 112.5 mg/m2; P < .0001). Median cisplatin total dose was similar for patients with a chemotherapy response or stable disease and threefold greater than for patients with progressive disease for both regimens. Although patients with chemotherapy response and stable disease had similar survival outcomes for both CAP and VP, the VP regimen had a higher proportion of patients without progressive disease (P = .004), which resulted in an overall survival advantage (P = .01).
The major prognostic factors for advanced NSCLC do not exert their influence on outcome by affecting deliverable chemotherapy DI. Regimen and treatment response determined total dose. Because stable disease patients usually outnumber responding patients in advanced NSCLC trials, controlled studies should be performed that allow assessment of the impact of total received dose on outcome according to response status.
加拿大针对晚期非小细胞肺癌（NSCLC）的多中心试验报告称，与长春地辛-顺铂（VP）以及环磷酰胺、阿霉素和顺铂联合方案（CAP）相比，最佳支持治疗时化疗具有生存获益。我们检查了所接受的药物给药情况，以记录该患者群体中各治疗组的剂量强度（DI）和所给予药物的总剂量。
采用累积接受化疗量随时间变化的图表来评估不同治疗方案、主要预后因素及反应状态下的药物给药情况。
个体CAP患者所接受的DI范围较窄，中位数与方案相近。药物给药分析显示，在更强效的VP方案中，两种药物所接受的DI范围较宽，且所接受DI的中位数低于方案规定。VP方案中顺铂所接受DI的中位数仍高于CAP方案，但仅在方案治疗的前8周（分别为20和10mg/m²/周）；此后，持续接受的顺铂DI相同（10mg/m²/周）。各治疗方案中顺铂所接受DI的中位数不受分期、体能状态、既往体重减轻情况、性别或反应状态的影响。接受VP治疗的患者所接受顺铂的总剂量高于接受CAP治疗的患者（中位数分别为255mg/m²和112.5mg/m²；P < 0.0001）。对于化疗有反应或疾病稳定的患者，两种治疗方案中顺铂的总剂量中位数相似，且均为疾病进展患者的三倍。尽管化疗有反应和疾病稳定的患者在CAP和VP两种方案中的生存结果相似，但VP方案中无疾病进展的患者比例更高（P = 0.004），这导致了总体生存优势（P = 0.01）。
晚期NSCLC的主要预后因素并非通过影响可给予的化疗DI来影响预后。治疗方案和治疗反应决定了总剂量。由于在晚期NSCLC试验中疾病稳定的患者通常多于有反应的患者，因此应开展对照研究，以评估根据反应状态所接受的总剂量对预后的影响。
