title: Historic evidence and future directions in clinical trial therapy of solid tumors.
abstract: Although improved survival is the "gold standard" for proving clinical benefit of oncologic therapy, the U.S. Food and Drug Administration (FDA) has accepted significant results in clinical trials using surrogate endpoints as the basis for drug approval. One surrogate is the amount of tumor reduction, or tumor response. Although tumor shrinkage would seem to be a necessary precondition for improved survival, clinical studies of a variety of oncologic agents have not consistently demonstrated a correlation between the two in patients with renal cell carcinoma. Moreover, tumor response may not be an appropriate endpoint for evaluating the effects of the new targeted therapies, whose putative mechanisms are generally cytostatic rather than cytotoxic. Clinical trials suggest that some patients with other solid tumors, such as lung cancer, may derive clinical benefit from treatment that helps stabilize their disease. There is also controversy as to whether the Response Evaluation Criteria in Solid Tumors (RECIST) provides the most appropriate instrument for assessing tumor burden. Ultimately, use of a variety of endpoints as well as different trial designs may provide an adequate basis for investigating the benefits/risks of newer therapies.
authors.affiliation: Duke University Medical Center Durham, NC 27710, USA. gollo001@mc.duke.edu
authors.forename: Jared A
authors.initials: JA
authors.lastname: Gollob
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic / Q000379:methods*; D018450:Disease Progression; D018572:Disease-Free Survival; D017277:Drug Approval; D023381:Endpoint Determination; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents