title: Safety and efficacy of using a single agent or a phase II agent before instituting standard combination chemotherapy in previously untreated metastatic breast cancer patients: report of a randomized study--Cancer and Leukemia Group B 8642.
abstract: OBJECTIVE
  We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients.
  
  
  METHODS
  A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF.
  
  
  RESULTS
  The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm.
  
  
  CONCLUSIONS
  The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, 01655, USA. mary.costanza@banyan.ummed.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Costanza
authors.forename: R B
authors.initials: RB
authors.lastname: Weiss
authors.forename: I C
authors.initials: IC
authors.lastname: Henderson
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.forename: D A
authors.initials: DA
authors.lastname: Berry
authors.forename: C
authors.initials: C
authors.lastname: Cirrincione
authors.forename: E
authors.initials: E
authors.lastname: Winer
authors.forename: W C
authors.initials: WC
authors.lastname: Wood
authors.forename: E
authors.initials: E
authors.lastname: Frei
authors.forename: O R
authors.initials: OR
authors.lastname: McIntyre
authors.forename: R L
authors.initials: RL
authors.lastname: Schilsky
mesh_terms: D000225:Adenine; D000328:Adult; D000368:Aged; D000617:Aminoglycosides; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016190:Carboplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007094:Imides / Q000627:therapeutic use; D007546:Isoquinolines / Q000627:therapeutic use; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D053644:Naphthalimides; D009367:Neoplasm Staging; D063065:Organophosphonates; D011446:Prospective Studies; D016019:Survival Analysis; D016597:Trimetrexate / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; D063065:Organophosphonates; C037020:amonafide; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D000225:Adenine; D008558:Melphalan; D005472:Fluorouracil; D016597:Trimetrexate; C049904:elsamicin A