title: Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma.
abstract: BACKGROUND
  CBP501, a synthetic duodecapeptide, increases cisplatin influx into tumor cells through an interaction with calmodulin enhancing cisplatin cytotoxicity, and effects cell cycle progression by abrogating DNA repair at the G2 checkpoint. In phase I clinical trials of CBP501 alone or in combination with cisplatin, the most common toxicity was infusion-related urticaria. Activity of CBP501 plus cisplatin was observed in patients with ovarian cancer and mesothelioma, including some patients previously treated with cisplatin.
  
  
  METHODS
  Chemotherapy naïve patients with unresectable MPM were stratified by histology and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501 25mg/m(2) IV (Arm A) or pemetrexed/cisplatin alone (Arm B). The primary endpoint was progression free survival (PFS) at 4 months.
  
  
  RESULTS
  65 patients were randomized, and 63 were treated. Patient characteristics in the two arms were balanced. Based on independent radiology review of the treated population, 25/40 patients (63%) in Arm A and 9/23 (39%) in Arm B had PFS≥4mo; the median PFS was 5.1mo (95% CI, 3.9, 6.5) vs 3.4mo (2.5, 6.7). Median OS was 13.3mo (9.2, 16.3) in Arm A and 12.8 (6.5, 16.1) in Arm B. Adverse events were not different than expected from standard chemotherapy, and comparable in the two arms, aside from infusion reactions which occurred in 70% of patients treated with CBP501.
  
  
  CONCLUSIONS
  While this randomized phase II trial met its primary endpoint of PFS at 4 months, other parameters such as response rate and overall survival suggest that the addition of CBP501 does not improve the efficacy of standard chemotherapy for MPM.
authors.affiliation: Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. Electronic address: krugl@mskcc.org.
authors.forename: L M
authors.initials: LM
authors.lastname: Krug
authors.affiliation: Karmanos Cancer Center, Detroit, MI, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Wozniak
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Kindler
authors.affiliation: Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Feld
authors.affiliation: City of Hope Cancer Center, Duarte, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Koczywas
authors.affiliation: Hospital Maria Ferrer, Buenos Aires, Argentina.
authors.forename: J L
authors.initials: JL
authors.lastname: Morero
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Rodriguez
authors.affiliation: Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Ross
authors.affiliation: University of New Mexico, Albuquerque, NM, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Bauman
authors.affiliation: St. Petersburg Medical University, St. Petersburg, Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Orlov
authors.affiliation: Intermountain Healthcare, Salt Lake City, UT, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Ruckdeschel
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Mita
authors.affiliation: Centro Oncologico de Rosario, Rosario, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Fein
authors.affiliation: ICON Clinical Research, North Wales, PA, USA.
authors.forename: X
authors.initials: X
authors.lastname: He
authors.affiliation: ICON Clinical Research, North Wales, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hall
authors.affiliation: CanBas Co., Ltd., Numazu City, Shizuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawabe
authors.affiliation: Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D010446:Peptide Fragments / Q000008:administration & dosage; D016896:Treatment Outcome; D020687:cdc25 Phosphatases / Q000008:administration & dosage
chemical_list: C517976:Cdc25C phosphatase (211-221); D005971:Glutamates; D010446:Peptide Fragments; D000068437:Pemetrexed; D006147:Guanine; D020687:cdc25 Phosphatases; D002945:Cisplatin
keywords: CBP501; CDC25C; Cisplatin; DNA repair; Malignant pleural mesothelioma; Randomized phase II trial