title: Similar efficacy for phase I trials in comparison with DTIC for advanced malignant melanoma: an analysis of melanoma outcomes in CTEP-sponsored phase I trials 1995-2011.
abstract: After ipilimumab, vemurafenib, and interleukin-2, standard of care chemotherapy for melanoma remains dacarbazine (response rate ∼9%). Despite this, many physicians hesitate to refer patients to phase I protocols given a perceived lack of clinical benefit and potential for harm. To better understand the validity of these perceptions, the experience of all patients with melanoma treated on phase I trials sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) from 1995 to 2011 were analyzed and compared with the pooled results of six contemporary phase III trials of dacarbazine. A total of 937 patients with melanoma were treated in 148 CTEP phase I trials. The majority were men with a median of two prior therapies (46% receiving prior dacarbazine). Response and clinical benefit rates in these trials were not clinically different from those of dacarbazine (phase I: 6.3 and 26.8% vs. dacarbazine: 8.8 and 27.9%) although grades 3 and 4 toxicity was significantly higher (54 vs. 28%). Efficacy and toxicity were generally consistent within phase I subgroups (targeted agents, immunotherapies, or chemotherapeutics) though targeted therapy was associated with a lower response rate, immunotherapy with lower clinical benefit rate, and chemotherapy with higher incidence of grade 4 toxicity. Thus, the perception of limited efficacy of phase I trials for patients with melanoma was disproven, whereas the perception of toxicity was observed. However, this difference in toxicity may have been largely because of the nature of phase I vs. phase III trials (i.e. more heavily pretreated) and because of the phase I trials often being multiagent as opposed to dacarbazine alone.
authors: Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. jason_luke@dfci.harvard.edu
authors: Jason J
authors: JJ
authors: Luke
authors: Lawrence V
authors: LV
authors: Rubinstein
authors: Gary L
authors: GL
authors: Smith
authors: S Percy
authors: SP
authors: Ivy
authors: Pamela J
authors: PJ
authors: Harris
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017326:Clinical Trials, Phase III as Topic; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine