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To the Editor:

H. Lee Moffitt Cancer Center, Tampa, FL

I read with much interest the article by Smorenburg et al,¹ and the accompanying editorial by Dr Egorin² in the January 15, 2003 issue of the Journal of Clinical Oncology. The search for the best method of dosing chemotherapy drugs is an important one, especially when it pertains to populations with highly variable body composition and functional reserve, such as older cancer patients. Dr Egorin wrote a thoughtful editorial; however, I believe that one of his arguments raises more questions than it answers. Dr Egorin criticizes the value of the average body-surface area (BSA) used in the study by Smorenburg et al, and he cites National Cancer Institute/Cancer Therapy Evaluation Program data showing an average BSA of 1.8 m² among the program’s patients, rather than 1.73 m², as used in the trial. However, the study by Smorenburg et al was conducted in the Netherlands. Given that the prevalence of obesity is much higher in the American population than in Europe, average American BSA is essentially irrelevant in evaluating Dutch data. Dr Egorin’s argument raises an interesting caveat about the use of flat dosing regimens. If one were to define a flat dose based on an American population and apply it to other populations, one would obtain a higher average drug exposure in European or Asian patients, with a potential for higher response rates and toxicity. This would put a tricky stumbling block into the design and interpretation of international studies. There is a general agreement that dosage based on BSA is an imperfect way of administering chemotherapy. However, is flat dosing the answer? Or would it instead be a better assessment of individual pharmacokinetic and pharmacodynamic patient parameters?

REFERENCES

1. Smorenburg C, Sparreboom A, Bontenbal M, et al: Randomized cross-over evaluation of body-surface area–based dosing versus flat-fixed dosing of paclitaxel. J Clin Oncol 21:197–202, 2003[Abstract/Free Full Text]

2. Egorin MJ: Horseshoes, hand grenades, and body-surface area–based dosing: Aiming for the target. J Clin Oncol 21:182–183, 2003[Free Full Text]

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