OBESITY AND THERAPY-RELATED TOXICITY IN PATIENTS TREATED FOR SMALL-CELL LUNG-CANCER

Background: Obese individuals have altered pharmacokinetics for many m edications when compared with the non-obese. For the oncologist treati ng an obese cancer patient, these changes in drug disposition may pote ntially cause increased therapy-related toxicity. As a consequence, on cologists frequently treat obese patients with dose reductions in an e ffort to decrease chemotherapy toxicity. However, little clinical data exist to either support or refute this policy. Purpose: The clinical course of a cohort of patients treated for small-cell lung cancer (SCL C) was evaluated to determine if the obese patients had an increase in therapy-related toxicity. Methods: The study sample included 262 pati ents with histologically confirmed SCLC treated in clinical trials fro m 1977 through 1993. Before 1986, patients with limited stage SCLC wer e treated with a cyclophosphamide-based regimen with (n = 47) or witho ut (n = 46) chest radiotherapy. Subsequent patients with limited stage disease (n = 54) received etoposide and cisplatin plus twice-daily ch est radiotherapy. Patients with extensive stage SCLC were randomly tre ated with standard-dose (n = 46) or high-dose etoposide plus cisplatin (n = 44); poor-risk patients with extensive stage disease (n = 25) we re assigned to standard dose etoposide plus cisplatin. For all patient s, actual body weight was used when determining initial doses of chemo therapy. The measure of relative weight was the body mass index (BMI), which was calculated from the pretreatment height and weight data. Th e BMI was evaluated both on a continuum and with patients grouped into BMI levels (normal, obese, and severely obese). Toxicity parameters w ere collected during induction chemotherapy and were compared with the BMI. In addition, the overall survival of the entire cohort was evalu ated, with patients divided into different groups based on their BMI l evel. Results: We performed 170 comparisons between the BMI as a conti nuum or the BMI level and the 15 toxicity parameters. There were no co nsistent associations of significance found between increasing BMI or BMI levels and increasing toxicity from therapy. When survival was eva luated, no statistically significant differences were found between th e survival of patients within the different BMI levels. Conclusions: I n this group of 262 patients with SCLC, obesity at the start of treatm ent was not associated with increased toxicity from treatment or a sho rtened survival. No support for empiric chemotherapy dose reductions b ased on ideal body weight was evident from this study.