title: Association of rash with outcomes in a randomized phase II trial evaluating cetuximab in combination with mitoxantrone plus prednisone after docetaxel for metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  Cetuximab (C), a chimeric monoclonal antibody that binds epidermal growth factor receptor (EGFR), is active against androgen-independent prostate cancer cell lines and might enhance the activity of chemotherapy. The efficacy of combining cetuximab with mitoxantrone (M) plus prednisone (MP) was evaluated in progressive metastatic castrate-resistant prostate cancer (CRPC) after receiving docetaxel.
  
  
  METHODS
  Patients with progression after receiving docetaxel were eligible and randomized 2:1 to CMP or MP. Therapy was mitoxantrone 12 mg/m(2) intravenously (I.V.) on day 1, oral prednisone 10 mg daily in both arms, and cetuximab 250 mg/m(2) I.V. (400 mg/m(2) day 1, cycle 1) on days 1, 8, and 15 in the CMP arm. Cycles were repeated every 21 days. Radiologic assessments of disease and PSA (prostate-specific antigen) occurred every 4 cycles. The primary endpoint was time to progression (TTP).
  
  
  RESULTS
  A total of 115 patients were enrolled, 75 in the CMP and 40 in the MP arm: the median TTP was 4.9 and 6.6 months, respectively; the measurable disease response rate was 2% and 4%, the PSA response rate 7.7% and 17.6%, and median survival 11.9 and 15.7 months, respectively. Key grade 3-4 toxicities were neutropenia 44% and 25.6%, anemia 6.7% and 7.7%, thrombocytopenia 6.7% and 2.6%, and fatigue 8% in both arms. In an unplanned exploratory analysis, median TTP with (n = 24) and without rash (n = 51) in the CMP arm was 10.3 months vs. 2.8 months (P = .004). On multivariable analysis,rash was significantly associated with TTP (hazard ratio [HR] = 0.43; P = .01).
  
  
  CONCLUSIONS
  The treatment with CMP is not recommended in unselected men with docetaxel-treated CRPC, although rash might help develop tailored therapy.
authors.affiliation: US Oncology Research, McKesson Specialty Health, The Woodlands, TX, USA. Mark.Fleming@USOncology.com
authors.forename: Mark T
authors.initials: MT
authors.lastname: Fleming
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Michael
authors.initials: M
authors.lastname: Kolodziej
authors.forename: Sanjay
authors.initials: S
authors.lastname: Awasthi
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Danko
authors.initials: D
authors.lastname: Martincic
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Rastogi
authors.forename: Steven R
authors.initials: SR
authors.lastname: Rousey
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Weinstein
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: William R
authors.initials: WR
authors.lastname: Berry
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Boehm
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
authors.forename: Mary A
authors.initials: MA
authors.lastname: Rauch
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000068818:Cetuximab; D000077143:Docetaxel; D005076:Exanthema / Q000139:chemically induced* / Q000188:drug therapy; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D008942:Mitoxantrone; D000068818:Cetuximab; D011241:Prednisone