Annals of Oncology 7:1065-1070, 1996
© 1996 European Society for Medical Oncology
research-article |
Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer
1Centre Jean Perrin Clermont-Ferrand
2Sanofi Winthrop Gentilly
3Debiopharm, Charenton Le Pont
4Höpital paul Brousse Villejuif, France
Correspondence to: Philippe Chollet, MD Centre Jean Perrin 58, rue Montalembert 63011 Clermont-Ferrand France
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.
MATERIALS AND 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.
CONCLUSION:: 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 crossresistance and a differential clinical toxicity prome 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.
advanced ovarian cancer, oxaliplatin, salvage therapy
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