Obesity and therapy-related toxicity in patients treated for small-cell lung cancer

Obese individuals have altered pharmacokinetics for many medications when compared with the non-obese. For the oncologist treating an obese cancer patient, these changes in drug disposition may potentially cause increased therapy-related toxicity. As a consequence, oncologists frequently treat obese patients with dose reductions in an effort to decrease chemotherapy toxicity. However, little clinical data exist to either support or refute this policy.

The clinical course of a cohort of patients treated for small-cell lung cancer (SCLC) was evaluated to determine if the obese patients had an increase in therapy-related toxicity.

The study sample included 262 patients with histologically confirmed SCLC treated in clinical trials from 1977 through 1993. Before 1986, patients with limited stage SCLC were treated with a cyclophosphamide-based regimen with (n = 47) or without (n = 46) chest radiotherapy. Subsequent patients with limited stage disease (n = 54) received etoposide and cisplatin plus twice-daily chest radiotherapy. Patients with extensive stage SCLC were randomly treated with standard-dose (n = 46) or high-dose etoposide plus cisplatin (n = 44); poor-risk patients with extensive stage disease (n = 25) were assigned to standard dose etoposide plus cisplatin. For all patients, actual body weight was used when determining initial doses of chemotherapy. The measure of relative weight was the body mass index (BMI), which was calculated from the pretreatment height and weight data. The BMI was evaluated both on a continuum and with patients grouped into BMI levels (normal, obese, and severely obese). Toxicity parameters were collected during induction chemotherapy and were compared with the BMI. In addition, the overall survival of the entire cohort was evaluated, with patients divided into different groups based on their BMI level.

We performed 170 comparisons between the BMI as a continuum or the BMI level and the 15 toxicity parameters. There were no consistent associations of significance found between increasing BMI or BMI levels and increasing toxicity from therapy. When survival was evaluated, no statistically significant differences were found between the survival of patients within the different BMI levels.

In this group of 262 patients with SCLC, obesity at the start of treatment was not associated with increased toxicity from treatment or a shortened survival. No support for empiric chemotherapy dose reductions based on ideal body weight was evident from this study.