Phase I study of paclitaxel and uracil plus tegafur combination in patients with pretreated metastatic breast cancer

Drug sequencing based on preclinical modelling studies

A. Passardi, R. Maltoni, C. Milandri, L. Cecconetto, I. Massa, W. Zoli, A. Tesei, F. Fabbri, O. Nanni, D. Amadori

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8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)118-124
Number of pages7
JournalOncology
Volume72
Issue number1-2
DOIs
Publication statusPublished - Nov 2007

Fingerprint

Tegafur
Uracil
Paclitaxel
Breast Neoplasms
Leucovorin
Pharmaceutical Preparations
Maximum Tolerated Dose
Asthenia
Taxoids
Mucositis
Paresthesia
Anthracyclines
Myalgia
Nausea
Liver

Keywords

  • Leucovorin
  • Metastatic breast cancer
  • Paclitaxel
  • Phase I study
  • Tegafur
  • Translational research
  • Uracil

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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title = "Phase I study of paclitaxel and uracil plus tegafur combination in patients with pretreated metastatic breast cancer: Drug sequencing based on preclinical modelling studies",
abstract = "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.",
keywords = "Leucovorin, Metastatic breast cancer, Paclitaxel, Phase I study, Tegafur, Translational research, Uracil",
author = "A. Passardi and R. Maltoni and C. Milandri and L. Cecconetto and I. Massa and W. Zoli and A. Tesei and F. Fabbri and O. Nanni and D. Amadori",
year = "2007",
month = "11",
doi = "10.1159/000111130",
language = "English",
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TY - JOUR

T1 - Phase I study of paclitaxel and uracil plus tegafur combination in patients with pretreated metastatic breast cancer

T2 - Drug sequencing based on preclinical modelling studies

AU - Passardi, A.

AU - Maltoni, R.

AU - Milandri, C.

AU - Cecconetto, L.

AU - Massa, I.

AU - Zoli, W.

AU - Tesei, A.

AU - Fabbri, F.

AU - Nanni, O.

AU - Amadori, D.

PY - 2007/11

Y1 - 2007/11

N2 - 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.

AB - 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.

KW - Leucovorin

KW - Metastatic breast cancer

KW - Paclitaxel

KW - Phase I study

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KW - Translational research

KW - Uracil

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