Phase II study of a new vinca alkaloid derivative, S12363, in advanced breast cancer.

Abstract

Vinca alkaloids are widely used in the medical treatment of breast cancer. Our study aimed to evaluate the therapeutic activity of a new vinca alkaloid derivative, S12363 (vinfosiltine), which is 36 and 72 times more cytotoxic in vitro than vincristine and vinblastine, respectively. Because phase I studies did not allow a choice of the best treatment schedule, a randomization was performed between two schedules with the same dose intensity, that is, 0.3 mg/m2 given weekly or 0.6 mg/m2 given every 2 weeks. A total of 16 patients with advanced breast cancer who had failed a first-line treatment without any vinca alkaloid were entered in the study. Additionally, 6 women received the bimonthly regimen as first-line treatment of advanced breast cancer. Altogether, 17 patients received, prior to vinfosiltine, an anthracycline-based regimen given either as adjuvant (n = 4) or as first-line palliative treatment (n = 13). All 22 patients were evaluable for both toxicity and response. Neutropenia was the main toxic event (maximal toxicity per patient) with grade 3 (WHO) toxicity developing in 7/22 patients and grade 4, in 8/22. Other severe toxicities included leukopenia (n = 9), anemia (n = 1), diarrhea (n = 1), constipation (n = 1), and fatigue (n = 1). No patient achieved a complete or partial response. Vinfosiltine does not appear to have significant single-agent activity in advanced breast cancer at the doses and the schedules used in our study.

• Authors: A Adenis, J M Pion, P Fumoleau, P Pouillart, M Marty, B Giroux, J Bonneterre
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 35 Issue 6 Pg. 527-8 ( 1995) ISSN: 0344-5704 [Print] Germany
• PMID: 7882462 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents, Phytogenic
• Vinca Alkaloids
• S 12363

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy)
• Female
• Humans
• Injections, Intravenous
• Middle Aged
• Neutropenia (chemically induced)
• Vinca Alkaloids (administration & dosage, adverse effects, therapeutic use)