Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer

• Published in: Annals of oncology Vol. 7; no. 10; pp. 1065 - 1070
• Main Authors: Chollet, P., Bensmaïne, M. A., Brienza, S., Deloche, C., Curé, H., Caillet, H., Cvitkovic, E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.1996
• Subjects: Adult; advanced ovarian cancer; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Biological and medical sciences; Carcinoma - drug therapy; Carcinoma - mortality; Chemotherapy; Female; Humans; Medical sciences; Middle Aged; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - mortality; Oxaliplatin; Pharmacology. Drug treatments; salvage therapy; Survival Rate; Antineoplastic agent; Human; Treatment efficiency; Malignant tumor; Female genital diseases; Ovarian diseases; Ovary; Chemotherapy; Oxaliplatin; Treatment; Female; Salvage treatment; Platinum II Complexes
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/oxfordjournals.annonc.a010500

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.