Phase II study of vinorelbine administered by 96-hour infusion in patients with advanced breast carcinoma.

Abstract

BACKGROUND:

Vinorelbine given by weekly bolus injection is active and less toxic than bolus vinblastine in the treatment of patients with metastatic breast carcinoma. Vinblastine given by 5-day continuous infusion showed a steep dose-response curve. Pharmacokinetic studies of vinorelbine showed that it is possible to achieve a comparable antitumor effect with a smaller amount of the drug if it is given by continuous infusion. The purpose of this study was to determine the efficacy of vinorelbine given by 96-hour continuous infusion to patients with refractory metastatic breast carcinoma patients.

METHODS:

Between May 1996 and August 1997, 47 patients with metastatic breast carcinoma were registered into the study. All patients previously had received doxorubicin and 70% had undergone prior paclitaxel treatment. Approximately 56% of the patients had >/=2 metastatic sites. All patients received vinorelbine according to the following dose schedule: 8 mg bolus followed by 11 mg/m(2) by continuous infusion over 24 hours every 4 days every 3 weeks.

RESULTS:

Forty-four patients were evaluable for response. A total of 193 cycles were administered. The overall response rate was 16% (2 patients achieved a complete response and 5 patients achieved a partial response). The median duration of response was 4.3 months and the median overall survival was 8.6 months. Patients with visceral metastases and/or multiple sites of involvement had shorter durations of response than patients with only soft tissue disease or single-site metastasis (3.1 months vs. 4. 9 months) and shorter overall survival (8.1 months vs. 12 months). Dose reductions were necessary due to cumulative stomatitis and/or fatigue in 12 cycles and neutropenia and/or infection in 13 cycles.

CONCLUSIONS:

Due to toxicity, a revised maximum tolerated dose for continuous infusion vinorelbine is proposed by the authors: 8 mg intravenously over 10 minutes followed by 10 mg/m(2) by continuous infusion over 24 hours every 4 days. The current dose schedule did not offer an advantage either in response rates or survival over the weekly vinorelbine bolus injection in doxorubicin-resistant and paclitaxel-resistant patients.

• Authors: N K Ibrahim, Z Rahman, V Valero, J Willey, R L Theriault, A U Buzdar, J L Murray 3rd, R Bast, G N Hortobagyi
• Journal: Cancer (Cancer) Vol. 86 Issue 7 Pg. 1251-7 (Oct 01 1999) ISSN: 0008-543X [Print] United States
• PMID: 10506711 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1999 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Vinblastine
• Doxorubicin
• Paclitaxel
• Vinorelbine

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Agents, Phytogenic (administration & dosage, toxicity)
• Breast Neoplasms (drug therapy, mortality)
• Doxorubicin (administration & dosage)
• Drug Resistance
• Female
• Humans
• Infusions, Intravenous
• Middle Aged
• Neoplasm Metastasis
• Paclitaxel (administration & dosage)
• Survival Rate
• Treatment Outcome
• Vinblastine (administration & dosage, analogs & derivatives, toxicity)
• Vinorelbine