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.

11055 Purpose: Dosing of breast cancer adjuvant chemotherapy in obese women varies substantially, with up to 40% of obese women receiving reduced (compared to full weight-based) doses. Such variation indicates uncertainty about best practices. This study reports changes over time in protocol-specified dose determinations in heavy patients. Methods: The National Cancer Institute database of cooperative group trials was used to identify completed clinical trials of non-myeloablative breast cancer adjuvant chemotherapy. Dose determinations specified in each protocol were categorized into one of four groups: 1) full weight-based dosing, 2) dose reduction in heavy patients (ideal or corrected body weight used to calculate body surface area, BSA), 3) dosing in heavy patients left to physician’s discretion, or 4) no specific instructions. Results: Of 110 eligible clinical trial protocols identified, 61 (55%) were retrieved. Of the 16 protocols initiated before 1985, 15 (94%) either did not address dose determination (n = 6) or specified dose reduction (n = 9) in heavy patients. Of the 45 protocols initiated after 1985, 26 (58%) specified full weight-based dosing, 13 (29%) specified dose reductions, 4 (9%) left dosing in heavy women to the physician’s discretion, and 3 (7%) had no specific instructions for dose determinations in heavy patients. The difference in the use of full weight based doses before and after 1985 was statistically significant (p value = 0.0003, 2-sided Fisher’s exact test). One of the cooperative groups, which contributed 10 of the 45 (22%) clinical trial protocols since 1985, specifies a maximum BSA of 2.0 m2 for cyclophosphamide and doxorubicin in all protocols. Conclusions: Over the last two decades, dose determinations in clinical trial protocols have, with the exception of one cooperative group, specified use of actual body weight. Present-day dose reductions in obese patients who are not participating in clinical trials suggest a lack of diffusion of information about optimal dosing in obesity. The continued practice of limiting the doses of cyclophosphamide and doxorubicin in patients with a BSA over 2.0 m2 in the protocols of one cooperative group may contribute to persistent uncertainty about optimal dosing in heavy patients. No significant financial relationships to disclose.

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