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.

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.