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

Research output: Contribution to journalArticle

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

KW - Tegafur

KW - Translational research

KW - Uracil

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