Phase I study of paclitaxel and uracil plus tegafur combination in patients with pretreated metastatic breast cancer: drug sequencing based on preclinical modelling studies.
OBJECTIVE
Taxanes and fluoropyrimidines are active in metastatic breast cancer (MBC), and their combination has proven effective in anthracycline-refractory patients. We conducted a phase I study to determine the maximum tolerated dose (MTD) of uracil plus tegafur (UFT) given in combination with leucovorin (LV) and paclitaxel (Pacl) in patients with refractory MBC.


METHODS
Pacl was infused at a fixed dose of 150 mg/m2 on day 1. UFT, at doses escalated by 50 mg/m2 starting from 200 mg/m2 . day, and LV, at a fixed dose of 90 mg/day, were given orally every 8 h for 11 days (days 3-13). Cohorts of at least 3 patients were treated at each dose level, and if 1 experienced dose-limiting toxicity (DLT), a maximum of 3 additional patients were added at the same dose level. MTD was reached if 2 out of the 6 patients experienced DLT.


RESULTS
Sixteen patients were enrolled in the study. The most important toxicity observed was hematological. Nonhematological toxicities were paresthesia and myalgia, asthenia, nausea, and mucositis. DLT occurred in only 1 patient (grade 3 hepatic toxicity).


CONCLUSIONS
The recommended dose for a subsequent phase II trial is Pacl 150 mg/m2 on day 1, and UFT 300 mg/m2 and LV 90 mg on days 3-13, every 2 weeks.
Passardi
A
A
Department of Medical Oncology, Morgagni-Pierantoni Hospital, Forlì, Italy. sandropass@libero.it
Maltoni
R
R
Milandri
C
C
Cecconetto
L
L
Massa
I
I
Zoli
W
W
Tesei
A
A
Fabbri
F
F
Nanni
O
O
Amadori
D
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D008962:Models, Theoretical; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
D005641:Tegafur; D014498:Uracil; D017239:Paclitaxel; D002955:Leucovorin