title: Phase 1 and 2 study of carboplatin and pralatrexate in patients with recurrent, platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.
abstract: BACKGROUND
  The objective of this phase 1 and 2 trial was to identify the appropriate dose of combined carboplatin and pralatrexate for patients with recurrent, platinum-sensitive ovarian, fallopian tube, and primary peritoneal cancer.
  
  
  METHODS
  In phase 1, patients received carboplatin (at an area under the curve of 5) and increasing doses of pralatrexate until the maximum-tolerated dose (MTD) of pralatrexate was achieved. The primary endpoint was the response rate. Additional endpoints were safety, response duration, progression-free survival, overall survival, and pharmacokinetics.
  
  
  RESULTS
  Thirty patients were enrolled in phase 1, and 20 were enrolled in phase 2. Of all 50 patients, 49 completed the study. The mean patient age was 59 years, and patients completed a median of 6 cycles. The MTD for pralatrexate was 105 mg/m2. The clinical benefit rate (complete responses plus partial responses plus stable disease) was 86%. Of 26 patients who received the MTD, 12 had a partial response, 11 had stable disease, and 2 had disease progression. The progression-free survival rate at 3 and 6 months was 87% and 79%, respectively; and the overall survival rate was 98% at 6 and 12 months and 66% at 24 months. Of 30 patients, 18 (60%) in phase 1 experienced an adverse event of any grade; and, of those, 4 patients (13%) had a grade 3 or greater adverse event. In phase 2, 12 patients (60%) had an adverse event of any grade, and 4 (20%) had grade 3 or greater toxicity. There was a significant reduction in the total body clearance of pralatrexate when it was received concurrently with carboplatin.
  
  
  CONCLUSIONS
  Most patients responded to carboplatin-pralatrexate combination. This regimen is well tolerated and effective in this patient population. Cancer 2016;122:3297-3306. © 2016 American Cancer Society.
authors.affiliation: Division of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts. mdelcarmen@partners.org.
authors.forename: Marcela G
authors.initials: MG
authors.lastname: Del Carmen
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jeff G
authors.initials: JG
authors.lastname: Supko
authors.affiliation: Department of Biostatistics, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Nora K
authors.initials: NK
authors.lastname: Horick
authors.affiliation: Division of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: J Alejandro
authors.initials: JA
authors.lastname: Rauh-Hain
authors.affiliation: Division of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Clark
authors.affiliation: Division of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Campos
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Carolyn N
authors.initials: CN
authors.lastname: Krasner
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Tina
authors.initials: T
authors.lastname: Atkinson
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
mesh_terms: D000328:Adult; D000368:Aged; D000630:Aminopterin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000473:pathology; D002296:Carcinosarcoma / Q000188:drug therapy / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000473:pathology; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D016190:Carboplatin; D000630:Aminopterin
keywords: carboplatin-pralatrexate; chemotherapy; pharmacokinetics; recurrent ovarian cancer