A phase I clinical trial of a combination of mitoxantrone, 5- fluorouracil, and high-dose leucovorin given on a day 1 and day 8 schedule to patients with metastatic breast cancer

Charles Vogel, E. G. Gomez

Research output: Contribution to journalArticle

Abstract

In a Phase I-II clinical trial, 19 ambulatory women with metastatic breast cancer were treated with a combination of mitoxantrone, 5-fluorouracil, and leucovorin (MFL). The planned schedule of mitoxantrone intravenously (i.v.) on day 1 with 5FU and leucovorin (days 1, 8, and 15) was better tolerated on a day 1 and day 8 schedule. Dose-limiting toxicity was found to be granulocytopenia with very little subjective toxicity encountered. Platelet toxicity and more profound granulocyte toxicity appeared to occur in patients with liver metastases. Since most patients did not have easily measurable disease, a response rate could not be determined, although at least four patients had probable antitumor responses. We conclude that doses of M (7.5 mg/m2 i.v. day 1) and 375 mg/m2 days 1 and 8 of F and L should be the starting doses for Phase II trials on this treatment schedule and should be well tolerated subjectively. Dose escalation and deescalation schemata should be included in a Phase II study design, recognizing that some patients may not encounter toxicity at these doses, while patients with liver metastases may develop inordinate toxicity.

Original languageEnglish
Pages (from-to)45-49
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume17
Issue number1
StatePublished - Jan 1 1994

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Mitoxantrone
Clinical Trials, Phase I
Leucovorin
Fluorouracil
Appointments and Schedules
Breast Neoplasms
Neoplasm Metastasis
Phase II Clinical Trials
Agranulocytosis
Liver
Granulocytes
Blood Platelets

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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abstract = "In a Phase I-II clinical trial, 19 ambulatory women with metastatic breast cancer were treated with a combination of mitoxantrone, 5-fluorouracil, and leucovorin (MFL). The planned schedule of mitoxantrone intravenously (i.v.) on day 1 with 5FU and leucovorin (days 1, 8, and 15) was better tolerated on a day 1 and day 8 schedule. Dose-limiting toxicity was found to be granulocytopenia with very little subjective toxicity encountered. Platelet toxicity and more profound granulocyte toxicity appeared to occur in patients with liver metastases. Since most patients did not have easily measurable disease, a response rate could not be determined, although at least four patients had probable antitumor responses. We conclude that doses of M (7.5 mg/m2 i.v. day 1) and 375 mg/m2 days 1 and 8 of F and L should be the starting doses for Phase II trials on this treatment schedule and should be well tolerated subjectively. Dose escalation and deescalation schemata should be included in a Phase II study design, recognizing that some patients may not encounter toxicity at these doses, while patients with liver metastases may develop inordinate toxicity.",
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