title: Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer.
abstract: BACKGROUND
  Platinum-containing chemotherapy combinations achieve high response rates in women with advanced ovarian cancer. Unfortunately, most patients need further therapeutic options. Oxaliplatin (L-OHP) is a diaminocyclohexane (DACH) platinum analog active against human and murine cells in vitro and in vivo, including ovarian cells lines, with non-cross resistance characteristics with first (CDDP) and second (CBDCA) generation platinum compounds. The single agent activity of oxaliplatin in 34 consecutive platinum-pretreated ovarian cancer patients, not eligible for other phase II trials, was explored in a compassionate use program framework in a single institution.
  
  
  METHODS
  Thirty-five patients (34 of them eligible) were treated by L-OHP at the median initial dose of 100 mg/sqm q 3 weeks (5 patients: 58-89 mg/m2; 24 patients: 90-100 mg/m2; 6 patients: 120-130 mg/m2) by short (30'-2 hours) i.v. infusion; the treatment was repeated every three weeks until treatment limiting toxicity or disease progression.
  
  
  RESULTS
  Thirty-one patients (median previous chemotherapy lines: 3) were evaluable for antitumoral activity, with a 29% objective response rate. According to Markman's criteria, objective partial responses were seen in six out of 13 evaluable potentially platinum-sensitive patients (46%) and three responses in the 18 evaluable platinum-resistant patients (17%). The tolerance was excellent, with no grade 3-4 (WHO) leukoneutropenia despite previous ABMT and abdominopelvic radiotherapy in six and eight cases, respectively. There was no renal or ototoxicity, and nausea/vomiting were moderate. The only grade 3 (WHO) peripheral neuropathy recorded concerned a patient with a neurotoxicity status grade 2 at baseline.
  
  
  CONCLUSIONS
  The 29% ORR single agent activity of oxaliplatin at hematological subtoxic doses in heavily pretreated ovarian cancer patients, with objective responses in platinum refractory patients, supports experimental data on non cross-resistance and a differential clinical toxicity profile to other available platinum compounds. The 12 month median overall survival of this poor prognosis patients cohort (62% platinum-refractory patients, median number of three previous chemotherapy lines) gives a strong empirical basis for the further exploration of oxaliplatin's role in confirmatory phase II and combination chemotherapy studies.
authors.affiliation: Centre Jean Perrin, Clermont-Ferrand, France.
authors.forename: P
authors.initials: P
authors.lastname: Chollet
authors.forename: M A
authors.initials: MA
authors.lastname: Bensmaïne
authors.forename: S
authors.initials: S
authors.lastname: Brienza
authors.forename: C
authors.initials: C
authors.lastname: Deloche
authors.forename: H
authors.initials: H
authors.lastname: Curé
authors.forename: H
authors.initials: H
authors.lastname: Caillet
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000077150:Oxaliplatin; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin