Quality-adjusted time without symptoms or toxicity analysis of adjuvant chemotherapy in non-small-cell lung cancer: an analysis of the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial.

PURPOSE: National Cancer Institute of Canada Clinical Trials Group JBR.10 demonstrated that adjuvant vinorelbine and cisplatin after resection of stage IB-II non-small-cell lung cancer (NSCLC) improved relapse-free and overall survival. However, many patients either are not referred for chemotherapy or decline treatment. To aid in treatment decision making, quality-adjusted survival estimates of the JBR.10 trial were derived using a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis. METHODS: Survival curves for treatment (N = 242) and observation groups (N = 240) were partitioned into three health states: time with >or= grade 2 (early or late) chemotherapy-related toxicity (TOX), time in relapse (REL), and time without toxicity or relapse (TWiST). Q-TWiST = u(TOX) x TOX + u(TWiST) x TWIST + u(REL) x REL, where weights u(TOX), u(TWIST), and u(REL) range from 0 to 1. Threshold utility analysis was performed to test the sensitivity of the results to changes in the weights. Weights were derived in an exploratory fashion using different methods. Methods included use of arbitrary values, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) quality-of-life data prospectively collected in JBR.10 (global assessment questions and symptom-based questions), and lastly weights European Quality of Life-Five Dimensions questionnaire collected from early-stage NSCLC (nontrial) patients after resection with discounting for toxicity and relapse. The alpha level was .05. RESULTS: Threshold utility analysis revealed that adjuvant chemotherapy was preferred for all possible weight values for relapse and toxicity (u(REL), u(TOX)), although the result was not always statistically significant. The adjuvant chemotherapy group had better Q-TWiST in the range of 5 to 6 additional months, which was statistically significant using all methods. CONCLUSION: Adjuvant chemotherapy in early-stage NSCLC improves quality-adjusted survival despite chemotherapy toxicity.

Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: a review of National Cancer Institute of Canada Clinical Trials Group trials.

PURPOSE: This study analyzed patients enrolled in two large, prospectively randomized trials of systemic chemotherapy (adjuvant/palliative setting) for non-small-cell lung Cancer (NSCLC). The main objective was to determine if age and/or the burden of chronic medical conditions (comorbidity) are independent predictors of survival, treatment delivery, and toxicity. PATIENTS AND METHODS: Baseline comorbid conditions were scored using the Charlson comorbidity index (CCI), a validated measure of patient comorbidity that is weighted according to the influence of comorbidity on overall mortality. The CCI score (CCIS) was correlated with demographic data,(ie, age, sex, race), performance status (PS), histology, cancer stage, patient weight, hemoglobin, alkaline phosphatase, lactate dehydrogenase, outcomes of chemotherapy delivery (ie, type, total dose, and dose intensity), survival, and response. RESULTS: A total of 1,255 patients were included in this analysis. The median age was 61 years (range, 34 to 89 years); 34% of patients were elderly (at least 65 years of age); and 31% had comorbid conditions at randomization. Twenty-five percent of patients had a CCIS of 1, whereas 6% had a CCIS of 2 or greater. Elderly patients were more likely to have a CCIS equal to or greater than 1 compared with younger patients (42% v 26%; P < .0001), as were male patients (35% v 21%; P < .0001) and patients with squamous histology (36% v 29%; P = .001). Although age did not influence overall survival, the CCIS appeared prognostic (CCIS 1 v 0; hazard ratio 1.28; 95%CI, 1.09 to 1.5; P = .003). CONCLUSION: In these large, randomized trials, the presence of comorbid conditions (CCIS > or = 1), rather than age more than 65 years, was associated with poorer survival.