title: A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer.
abstract: OBJECTIVE
  Carboplatin-based combinations are commonly used in platinum-sensitive ovarian cancer (PSOC). Pemetrexed in combination with carboplatin has been shown to be feasible in a phase I study in PSOC. The primary objective of this subsequent phase II study was to determine the overall response rate (ORR; defined by Response Evaluation Criteria in Solid Tumors) of this combination in patients with recurrent PSOC. Secondary objectives included progression-free survival (PFS), overall survival (OS), and toxicity.
  
  
  METHODS
  Patients with PSOC (defined by recurrence ≥ 6 months after completion of up to two lines of prior platinum-based therapy), measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. Pemetrexed 500 mg/m(2) was administered as a 10-minute infusion followed by carboplatin AUC 6 as a 30-minute infusion on day 1 of a 21-day cycle.
  
  
  RESULTS
  Sixty-six patients were treated. Of the 61 patients evaluable for response, there were 20 responders (one complete response and 19 partial responses), for an ORR of 32.8% (95% CI: 21.3%, 46.0%). For the intent-to-treat population (all 66 patients), the median PFS was 9.4 months (95% CI: 8.3, 11.1), with 22.7% censoring. Median OS was not reached due to the high censoring rate. There was one drug-related death (multi-organ failure). The most common drug-related grade 3/4 toxicities were neutropenia (39.4%), thrombocytopenia (24.2%), carboplatin hypersensitivity (9.1%), nausea (6.1%), and vomiting (6.1%).
  
  
  CONCLUSIONS
  Carboplatin AUC 6 and pemetrexed 500 mg/m(2) has a low incidence of serious toxicities. Defining the platinum-based combination with the best therapeutic index would require a prospective phase III study.
authors: Charité University Hospital, Department of Gynecology and Obstetrics, Virchow-Klinikum, Berlin, Germany. sehouli@aol.com
authors: Jalid
authors: J
authors: Sehouli
authors: Ana Maria
authors: AM
authors: Alvarez
authors: Shokoufeh
authors: S
authors: Manouchehrpour
authors: Prafull
authors: P
authors: Ghatage
authors: Cezary
authors: C
authors: Szczylik
authors: Annamaria
authors: A
authors: Zimmermann
authors: Thomas
authors: T
authors: Bauknecht
authors: Katherine Y
authors: KY
authors: Look
authors: Gultan
authors: G
authors: Oskay-Öezcelik
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D015996:Survival Rate
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin