CARBOPLATIN ORAL ETOPOSIDE PERSONALIZED DOSING IN ELDERLY NONSMALL CELL LUNG-CANCER PATIENTS

The toxicity and therapeutic activity, including the effect on quality of life, of the carboplatin-oral etoposide combination, given with an intrapatient dose escalation, was tested in 38 non-small cell lung ca ncer (NSCLC) patients aged over 70 years, and in 8 younger patients wi th a performance status of 2. In the absence of grade 3-4 toxicity, do ses were escalated as follows: first course (carboplatin AUC 4; etopos ide 50 mg twice daily orally days 1-14); second course (carboplatin AU C 5; etoposide 50 mg twice daily orally days 1-14); third course (carb oplatin AUC 5; etoposide 50 mg twice daily orally days 1-21). A total of 141 chemotherapy cycles were delivered. The treatment was, in gener al, well tolerated and no toxic deaths occurred. More than 60% of pati ents received 100% of the planned dose intensity. Transient: grade 4 n eutropenia or thrombocytopenia occurred in 6 and 2 patients, respectiv ely, but only 2 patients had to be hospitalised because of fever. All patients were evaluated for activity on an 'intention to treat basis'. Ten partial responses and 20 stable disease were recorded, for an ove rall response rate of 22% (95% confidence interval (CI) = 11-36). 9/38 (24%; 95% CI = 12-41) elderly patients obtained a partial response. T he median response duration was 4 months. A quality of life improvemen t was observed in 19 of the 46 enrolled patients (41%; 95% GI = 27-57) , and 15/46 (33%; 95% CI = 19-48) showed a performance status improvem ent. The quality of life score improved in 17/38 (45%) elderly patient s, 8/10 responders and 11/20 patients with stable disease showed a con comitant improvement in quality of life. At a median potential follow- up of 16 months (range 2-21), 31 patients had had progression of disea se and 23 had died, for a median time to progression (TTP) and overall survival (OS) of 5 and 10 months, respectively. The median survival t ime was 11 months in elderly patients. The median time to subjective i mpairment (TSI) was 6 months (7 months in the elderly group). One-year estimated TTP, TSI and OS rates were 22, 29 and 41%, respectively. At multivariate Cox analysis, a > 25% improvement in the quality of Life score was more predictive of a better survival outcome than the respo nse achievement. (C) 1998 Elsevier Science Ltd. All rights reserved.