A phase II trial of split, low-dose docetaxel and low-dose capecitabine

A tolerable and efficacious regimen in the first-line treatment of patients with HER2/neu-negative metastatic breast cancer

Orlando Silva, Gilberto Lopes, Daniel Morgenzstern, Christopher Lobo, Philomena Doliny, Edgardo Santos, Sakher Abdullah, Umang Gautam, Isildinha Reis, Catherine Welsh, Joyce M Slingerland, Judith Hurley, Stefan Gluck

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Successful therapeutic regimens in metastatic breast cancer (MBC) must balance efficacy and tolerability. Docetaxel/capecitabine is an active and commonly used doublet in this setting. Docetaxel upregulates thymidine Phosphorylase and thus potentiates the antitumor effects of capecitabine. A schedule with split, low-dose docetaxel in combination with low-dose capecitabine could improve the therapeutic index of this regimen without compromising its clinical activity. Patients and Methods: Patients with previously untreated HER2/neu-negative MBC were eligible. Treatment consisted of docetaxel 25 mg/m2 on days 1 and 8 in combination with capecitabine 750 mg/m2 twice daily on days 1-14 of a 3-week cycle. Thirty-nine women were enrolled. Median age was 55 years (range, 36-75 years). Fourteen patients had triple-negative disease. Sites of metastasis were as follows: bone (n = 27); liver (n = 15); lung (n = 17); nonregional chest (n = 4); lymph nodes (n = 2); and skin (n = 1). Six patients had bone-only disease. All subjects had a performance status of 0/1. A total of 329 cycles were administered (median, 6; range, 1-50). Results: Of 37 patients who received study treatment, 32 had evaluable disease, 1 had a complete response, and 15 had a partial response (overall response rate was 50% in evaluable patients and 43% in the intent-to-treat analysis). Six patients had stable disease. The overall clinical benefit rate was 69% for patients with evaluable disease and 60% overall. Fifteen patients had disease that progressed or had been withdrawn from study at the time of first evaluation. With a median follow-up of 25 months, median time to treatment failure was 4.25 months (95% CI, 1.5-7 months), and median overall survival has not yet been reached. Toxicity was moderate: 15 patients (41%) had grade 3/4 adverse events. Conclusion: Split, low-dose docetaxel and low-dose capecitabine is an active combination in the first-line treatment of patients with MBC. Toxicity with this schedule was manageable, making it an attractive regimen for further study in combination with targeted agents.

Original languageEnglish
Pages (from-to)162-167
Number of pages6
JournalClinical Breast Cancer
Volume8
Issue number2
DOIs
StatePublished - Jan 1 2008

Fingerprint

docetaxel
Breast Neoplasms
Therapeutics
Appointments and Schedules
Capecitabine
Thymidine Phosphorylase

Keywords

  • Anemia
  • Bone metastasis
  • Thymidine phosphorylase
  • Time to treatment failure

ASJC Scopus subject areas

  • Cancer Research

Cite this

A phase II trial of split, low-dose docetaxel and low-dose capecitabine : A tolerable and efficacious regimen in the first-line treatment of patients with HER2/neu-negative metastatic breast cancer. / Silva, Orlando; Lopes, Gilberto; Morgenzstern, Daniel; Lobo, Christopher; Doliny, Philomena; Santos, Edgardo; Abdullah, Sakher; Gautam, Umang; Reis, Isildinha; Welsh, Catherine; Slingerland, Joyce M; Hurley, Judith; Gluck, Stefan.

In: Clinical Breast Cancer, Vol. 8, No. 2, 01.01.2008, p. 162-167.

Research output: Contribution to journalArticle

Silva, Orlando ; Lopes, Gilberto ; Morgenzstern, Daniel ; Lobo, Christopher ; Doliny, Philomena ; Santos, Edgardo ; Abdullah, Sakher ; Gautam, Umang ; Reis, Isildinha ; Welsh, Catherine ; Slingerland, Joyce M ; Hurley, Judith ; Gluck, Stefan. / A phase II trial of split, low-dose docetaxel and low-dose capecitabine : A tolerable and efficacious regimen in the first-line treatment of patients with HER2/neu-negative metastatic breast cancer. In: Clinical Breast Cancer. 2008 ; Vol. 8, No. 2. pp. 162-167.
@article{40dd745c3920402ebc91a7f73f971fd0,
title = "A phase II trial of split, low-dose docetaxel and low-dose capecitabine: A tolerable and efficacious regimen in the first-line treatment of patients with HER2/neu-negative metastatic breast cancer",
abstract = "Background: Successful therapeutic regimens in metastatic breast cancer (MBC) must balance efficacy and tolerability. Docetaxel/capecitabine is an active and commonly used doublet in this setting. Docetaxel upregulates thymidine Phosphorylase and thus potentiates the antitumor effects of capecitabine. A schedule with split, low-dose docetaxel in combination with low-dose capecitabine could improve the therapeutic index of this regimen without compromising its clinical activity. Patients and Methods: Patients with previously untreated HER2/neu-negative MBC were eligible. Treatment consisted of docetaxel 25 mg/m2 on days 1 and 8 in combination with capecitabine 750 mg/m2 twice daily on days 1-14 of a 3-week cycle. Thirty-nine women were enrolled. Median age was 55 years (range, 36-75 years). Fourteen patients had triple-negative disease. Sites of metastasis were as follows: bone (n = 27); liver (n = 15); lung (n = 17); nonregional chest (n = 4); lymph nodes (n = 2); and skin (n = 1). Six patients had bone-only disease. All subjects had a performance status of 0/1. A total of 329 cycles were administered (median, 6; range, 1-50). Results: Of 37 patients who received study treatment, 32 had evaluable disease, 1 had a complete response, and 15 had a partial response (overall response rate was 50{\%} in evaluable patients and 43{\%} in the intent-to-treat analysis). Six patients had stable disease. The overall clinical benefit rate was 69{\%} for patients with evaluable disease and 60{\%} overall. Fifteen patients had disease that progressed or had been withdrawn from study at the time of first evaluation. With a median follow-up of 25 months, median time to treatment failure was 4.25 months (95{\%} CI, 1.5-7 months), and median overall survival has not yet been reached. Toxicity was moderate: 15 patients (41{\%}) had grade 3/4 adverse events. Conclusion: Split, low-dose docetaxel and low-dose capecitabine is an active combination in the first-line treatment of patients with MBC. Toxicity with this schedule was manageable, making it an attractive regimen for further study in combination with targeted agents.",
keywords = "Anemia, Bone metastasis, Thymidine phosphorylase, Time to treatment failure",
author = "Orlando Silva and Gilberto Lopes and Daniel Morgenzstern and Christopher Lobo and Philomena Doliny and Edgardo Santos and Sakher Abdullah and Umang Gautam and Isildinha Reis and Catherine Welsh and Slingerland, {Joyce M} and Judith Hurley and Stefan Gluck",
year = "2008",
month = "1",
day = "1",
doi = "10.3816/CBC.2008.n.017",
language = "English",
volume = "8",
pages = "162--167",
journal = "Clinical Breast Cancer",
issn = "1526-8209",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - A phase II trial of split, low-dose docetaxel and low-dose capecitabine

T2 - A tolerable and efficacious regimen in the first-line treatment of patients with HER2/neu-negative metastatic breast cancer

AU - Silva, Orlando

AU - Lopes, Gilberto

AU - Morgenzstern, Daniel

AU - Lobo, Christopher

AU - Doliny, Philomena

AU - Santos, Edgardo

AU - Abdullah, Sakher

AU - Gautam, Umang

AU - Reis, Isildinha

AU - Welsh, Catherine

AU - Slingerland, Joyce M

AU - Hurley, Judith

AU - Gluck, Stefan

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Background: Successful therapeutic regimens in metastatic breast cancer (MBC) must balance efficacy and tolerability. Docetaxel/capecitabine is an active and commonly used doublet in this setting. Docetaxel upregulates thymidine Phosphorylase and thus potentiates the antitumor effects of capecitabine. A schedule with split, low-dose docetaxel in combination with low-dose capecitabine could improve the therapeutic index of this regimen without compromising its clinical activity. Patients and Methods: Patients with previously untreated HER2/neu-negative MBC were eligible. Treatment consisted of docetaxel 25 mg/m2 on days 1 and 8 in combination with capecitabine 750 mg/m2 twice daily on days 1-14 of a 3-week cycle. Thirty-nine women were enrolled. Median age was 55 years (range, 36-75 years). Fourteen patients had triple-negative disease. Sites of metastasis were as follows: bone (n = 27); liver (n = 15); lung (n = 17); nonregional chest (n = 4); lymph nodes (n = 2); and skin (n = 1). Six patients had bone-only disease. All subjects had a performance status of 0/1. A total of 329 cycles were administered (median, 6; range, 1-50). Results: Of 37 patients who received study treatment, 32 had evaluable disease, 1 had a complete response, and 15 had a partial response (overall response rate was 50% in evaluable patients and 43% in the intent-to-treat analysis). Six patients had stable disease. The overall clinical benefit rate was 69% for patients with evaluable disease and 60% overall. Fifteen patients had disease that progressed or had been withdrawn from study at the time of first evaluation. With a median follow-up of 25 months, median time to treatment failure was 4.25 months (95% CI, 1.5-7 months), and median overall survival has not yet been reached. Toxicity was moderate: 15 patients (41%) had grade 3/4 adverse events. Conclusion: Split, low-dose docetaxel and low-dose capecitabine is an active combination in the first-line treatment of patients with MBC. Toxicity with this schedule was manageable, making it an attractive regimen for further study in combination with targeted agents.

AB - Background: Successful therapeutic regimens in metastatic breast cancer (MBC) must balance efficacy and tolerability. Docetaxel/capecitabine is an active and commonly used doublet in this setting. Docetaxel upregulates thymidine Phosphorylase and thus potentiates the antitumor effects of capecitabine. A schedule with split, low-dose docetaxel in combination with low-dose capecitabine could improve the therapeutic index of this regimen without compromising its clinical activity. Patients and Methods: Patients with previously untreated HER2/neu-negative MBC were eligible. Treatment consisted of docetaxel 25 mg/m2 on days 1 and 8 in combination with capecitabine 750 mg/m2 twice daily on days 1-14 of a 3-week cycle. Thirty-nine women were enrolled. Median age was 55 years (range, 36-75 years). Fourteen patients had triple-negative disease. Sites of metastasis were as follows: bone (n = 27); liver (n = 15); lung (n = 17); nonregional chest (n = 4); lymph nodes (n = 2); and skin (n = 1). Six patients had bone-only disease. All subjects had a performance status of 0/1. A total of 329 cycles were administered (median, 6; range, 1-50). Results: Of 37 patients who received study treatment, 32 had evaluable disease, 1 had a complete response, and 15 had a partial response (overall response rate was 50% in evaluable patients and 43% in the intent-to-treat analysis). Six patients had stable disease. The overall clinical benefit rate was 69% for patients with evaluable disease and 60% overall. Fifteen patients had disease that progressed or had been withdrawn from study at the time of first evaluation. With a median follow-up of 25 months, median time to treatment failure was 4.25 months (95% CI, 1.5-7 months), and median overall survival has not yet been reached. Toxicity was moderate: 15 patients (41%) had grade 3/4 adverse events. Conclusion: Split, low-dose docetaxel and low-dose capecitabine is an active combination in the first-line treatment of patients with MBC. Toxicity with this schedule was manageable, making it an attractive regimen for further study in combination with targeted agents.

KW - Anemia

KW - Bone metastasis

KW - Thymidine phosphorylase

KW - Time to treatment failure

UR - http://www.scopus.com/inward/record.url?scp=43249115614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43249115614&partnerID=8YFLogxK

U2 - 10.3816/CBC.2008.n.017

DO - 10.3816/CBC.2008.n.017

M3 - Article

VL - 8

SP - 162

EP - 167

JO - Clinical Breast Cancer

JF - Clinical Breast Cancer

SN - 1526-8209

IS - 2

ER -