Breast cancer adjuvant chemotherapy dosing in obese patients

Abstract

BACKGROUND Substantial variation in adjuvant breast cancer chemotherapy dosing in obese women suggests that there is uncertainty about optimal practices. The purpose of this study was to investigate variations in dose determinations in clinical trial protocols and publications over the last 3 decades as potential sources of this uncertainty. METHODS The National Cancer Institute database was used to identify protocols of breast cancer adjuvant chemotherapy conducted by cooperative groups between 1970–2000, and these protocols were then obtained directly from the cooperative groups. Dose determinations were categorized in each protocol and in published reports from each clinical trial. Fisher exact tests were used to compare the proportions of protocols that used full weight‐based doses over time. RESULTS Protocol‐specified chemotherapy dosing was obtained for all of 44 eligible trials. A significant increase was identified in the use of full weight‐based doses in the later time period compared with the earlier (P = .004; 2‐sided Fisher exact test). A notable exception was 1 cooperative group that continues to require dose limitations for doxorubicin and cyclophosphamide in patients with a body surface area of more than 2.0 m2. Regardless of publication date, published reports of clinical trials rarely provide information on use of full or limited weight‐based doses. CONCLUSIONS Variations in dose determinations among clinical trial protocols and lack of information on use of full weight‐based doses in most publications are 2 likely sources of variation in chemotherapy dosing in obese women. Developing consensus and disseminating information on optimal chemotherapy dosing will likely reduce such variation and may improve survival among obese patients with breast cancer. Cancer 2008. © 2008 American Cancer Society.

Description of Current Practices of Empiric Chemotherapy Dose Adjustment in Obese Adult Patients

“…However, multiple retrospective analyses observed that obese women treated for breast cancer using ABW did not have increased toxicity compared with normal women. 17,19,20 Altering the number of CMs in our survey did not affect EDA.…”

“…17,18 An analysis of breast cancer adjuvant chemotherapy protocols from 1970 to 2000 also demonstrated this change over time. 19 Before 1984, 95% of these trials permitted use of EDA for obesity; since 1984, that amount has decreased to 55%.…”

The impact of obesity on receipt of adjuvant chemotherapy for breast cancer in the National Comprehensive Cancer Network (NCCN) centers

“…Greenman et al recommended that given the increase in prevalence of obesity and extreme obesity, guideline-development groups should provide information on standard of care practices for dosing obese breast cancer patients who are receiving adjuvant chemotherapy [31]. This study provides preliminary evidence that in a select clinical setting, physician recommendations regarding use of adjuvant chemotherapy for breast cancer are not influenced by patient weight.…”

Pre-diagnosis body mass index and survival after breast cancer in the After Breast Cancer Pooling Project

“…From the treatment perspective, obese women may be underdosed for chemotherapy due to toxicity-related concerns, resulting in reduced therapeutic response and worse outcomes [47-49]. However, when we stratified the obese women in our cohort by receipt of chemotherapy, no prognostic risk differences were observed by chemotherapy status.…”