title: Objective responses in patients with malignant melanoma or renal cell cancer in early clinical studies do not predict regulatory approval.
abstract: OBJECTIVE
  Tumor responses in early-phase trials are used to determine whether new agents warrant further study. Given that spontaneous regressions are observed in melanoma and renal cell carcinoma, this study assessed whether tumor responses, particularly in these two tumor types, predict for future regulatory drug approval.
  
  
  METHODS
  The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and II trials in the following solid tumors: melanoma, renal cell carcinoma, non-small-cell lung cancer, breast cancer, ovarian cancer, colorectal cancer, and other solid tumors. Response rates were categorized and the relationship of these categories to the end point of regulatory drug approval was determined.
  
  
  RESULTS
  Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase II trials. Higher overall response rates in both phase I trials (P = 0.03) and phase II trials (P < 0.0001) were predictive of regulatory approval. However, response in melanoma or renal cell carcinoma was not predictive for either phase I or phase II studies.
  
  
  CONCLUSIONS
  For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive.
authors.affiliation: National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Goffin
authors.forename: Stefan
authors.initials: S
authors.lastname: Baral
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Dora
authors.initials: D
authors.lastname: Nomikos
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy; D017277:Drug Approval / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy