CORRESPONDENCE

RESPONSE: Re: Dose and Dose Intensity as Determinants of Outcome in the Adjuvant Treatment of Breast Cancer

D. A. Berry, D. R. Budman

Affiliations of authors: D. A. Berry, Cancer and Leukemia Group B Statistical Office, Durham, NC; D. R. Budman, North Shore University Hospital, Manhasset, NY.

Correspondence to: Daniel Budman, M.D., North Shore University Hospital, Don Monti Division of Oncology, Department of Medicine, 300 Community Dr., Manhasset, NY 11030.

Dr. Hryniuk asks a question and makes a valid point. As to whether ". . . higher dose is associated with better disease-free and overall survival" means higher total dose or higher dose intensity, we meant both. Both higher dose arms performed significantly better than the low-dose arm. However, a more appropriate comparison of the dose schedules requires consideration of tumor markers erbB-2 and p53 (1). Namely, intensive dose is more beneficial than either of the other doses in patients who are positive at these markers (singly or jointly) and there is little, if any, difference in any of the doses in patients who are negative on both markers.

Dr. Hryniuk suggests that it would have been better to have included a fourth arm in the trial design of Cancer and Leukemia Group B (CALGB) 8541. We agree that this inclusion would have been informative. However, it would have increased the trial's sample size by at least another 500 patients, or it would have required lowering the numbers of patients in the other arms, which would have decreased the power for comparing the various arms. An alternative approach could have been to design the study as a 2 x 2 factorial, with a fourth arm delivering the same total dose as the low-dose arm, but more than six instead of four cycles. Then, depending on the assumptions one makes about interactions between the two factors, the trial size might actually have decreased from the actual size of 1550 patients. The subsequent two generations of CALGB-designed breast adjuvant trials for women with lymph node-positive disease have used factorial designs to increase the informational value of these trials, while keeping the trial size manageable.

REFERENCE

1 Thor AD, Berry DA, Budman DR, Muss HB, Kute T, Henderson IC, et al. erbB-2, p-53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst 1998;90:1346-60.[Abstract/Free Full Text]



             
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