In Reply: The question raised by Dr Ross regarding
stable disease rates as a surrogate for clinical benefit is a valid one: anticancer
agents with mechanisms of action that are not cytotoxic may produce clinical
benefit by delaying tumor progression without effectively shrinking tumors.
For these agents, stable disease rates or time to tumor progression (TTP)
may represent more appropriate surrogates for clinical benefit than rates
of objective response such as tumor shrinkage. However, stable disease and
TTP can be reliably evaluated only with randomized trials. The measure of
these end points may be influenced by the underlying biology of the tumor,
the frequency of imaging studies, and potential investigator bias in the timing
of imaging studies, as well as the interpretation of clinical data. A slow-growing
tumor may appear to be of stable size for several months in a phase 1 trial;
without concurrent controls it is impossible to determine if the stability
of the tumor relates to its underlying biology or to the effects of the agent
under study. Because of these limitations, stable disease rates and TTP were
not uniformly reported in the types of trials we analyzed, and the Food and
Drug Administration has been hesitant to grant approvals based on these end
points outside of randomized trials.
Roberts TG, Goulart BH, Clark JW, Chabner BA. Trends in the Risks and Benefits to Patients With Cancer in Phase 1 Clinical Trials—Reply. JAMA. 2005;293(7):795. doi:10.1001/jama.293.7.795-b
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