Mitoxantrone, 5-fluorouracil and low-dose leucovorin in doxorubicin-resistant advanced breast cancer patients: a phase II study.
OBJECTIVE
Twenty-two anthracycline-resistant advanced breast cancer patients were entered from June 1995 till November 1997 in a phase II study to assess the activity and tolerability of second-line chemotherapy consisting of mitoxantrone, 5-fluorouracil and low-dose leucovorin.


METHODS
Patients were eligible if they failed to respond to doxorubicin-containing chemotherapy, given as first-line chemotherapy for metastatic disease. Treatment consisted of mitoxantrone, 12 mg/m2 iv infusion on day 1, and leucovorin, 50 mg iv 1 hr before 5-fluorouracil, 350 mg/m2 iv infusion on days 1-3, every three weeks.


RESULTS
Nineteen patients were eligible for response, 2 refused further therapy after 2 cycles, and 1 was excluded because grade 3 myelotoxicity developed during the first cycle. Partial remission of 15 months duration occurred in 1 patient, in 7/19 women disease remained stable with a median duration of 11 months (range, 5-24), and 11/19 patients experienced progressive disease. Median time to disease progression was 2 months (range, 0-17), and median survival was 8 months (range, 0-24). Toxicity was generally mild and acceptable. One patient was excluded because of grade 3 granulocytopenia and thrombocytopenia, and one due to cardiotoxicity assessed by the drop of left ventricular ejection fraction to more than 20% below the initial value.


CONCLUSIONS
In spite of the very low objective response rate, almost one-fourth of our anthracycline-resistant patients achieved a disease stabilization of 27 weeks duration during mitoxantrone-based second-line chemotherapy. Hence, mitoxantrone in combination with 5-fluorouracil, especially continuous infusion, should be further investigated in this setting, particularly if new and expensive drugs, considered the most active, are not readily available.
Susnjar
S
S
Department of Medical Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Yugoslavia. suska@Eunet.yu
Vasović
S
S
Nesković-Konstantinović
Z
Z
Stamatović
L
L
Lukić
V
V
Colaković
S
S
Mitrovic
L
L
Jelić
S
S
Radulović
S
S
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D004317:Doxorubicin; D008942:Mitoxantrone; D002955:Leucovorin; D005472:Fluorouracil