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	Full Text PDF PDA Full Text Editorial by Kurzrock, R. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Previous reviews of phase 1 oncology trials reported a rate of response to treatment of 4 to 6 percent and a toxicity-related death rate of 0.5 percent. These results may not reflect the rates in current phase 1 oncology trials.

Methods We reviewed all nonpediatric phase 1 oncology trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute between 1991 and 2002. We report the rates of response to treatment, of stable disease, of grade 4 toxic events, and of treatment-related deaths.

Results We analyzed 460 trials involving 11,935 participants, all of whom were assessed for toxicity and 10,402 of whom were assessed for a response to therapy. The overall response rate (i.e., for both complete and partial responses) was 10.6 percent, with considerable variation among trials. "Classic" phase 1 trials of single investigational chemotherapeutic agents represented only 20 percent of the trials and had a response rate of 4.4 percent. Studies that included at least one anticancer agent approved by the Food and Drug Administration constituted 46.3 percent of the trials and had a response rate of 17.8. An additional 34.1 percent of participants had stable disease or a less-than-partial response. The overall rate of death due to toxic events was 0.49 percent. Of 3465 participants for whom data on patient-specific grade 4 toxic events were available, 14.3 percent had had at least one episode of grade 4 toxic events.

Conclusions Overall response rates among phase 1 oncology trials are higher than previously reported, although they have not changed for classic phase 1 trials, and toxicity-related death rates have remained stable. Rates of response and toxicity vary, however, among the various types of phase 1 oncology trials.

Source Information

From the Department of Clinical Bioethics, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Md. (E.H., E.J.E., C.G.); the Memorial Sloan-Kettering Cancer Center, New York (M.S.M.); the Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville, Md. (L.G., S.Y., L.R., T.B., D.S.); and the Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo (S.Y.)

Address reprint requests to Dr. Grady at the Warren G. Magnuson Clinical Center, Bldg. 10, Rm. 1C118, National Institutes of Health, Bethesda, MD 20892-1156, or at cgrady{at}nih.gov.

Full Text of this Article

Related Letters:

Phase 1 Clinical Trials in Oncology
Rothschild B. B., King N. M.P., Muggia F. M., Sekine I., Tamura T., Miller M. J., Horstmann E., Emanuel E. J., Grady C., Kurzrock R., Benjamin R. S.
Extract | Full Text | PDF  
N Engl J Med 2005; 352:2451-2453, Jun 9, 2005. Correspondence

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