Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193)

J Clin Oncol. 2003 Feb 15;21(4):588-92. doi: 10.1200/JCO.2003.08.013.

Abstract

Purpose: Between February 1993 and September 1995, 739 patients with metastatic breast cancer were entered on an Intergroup trial (E1193) comparing doxorubicin (60 mg/m(2)), paclitaxel (175 mg/m(2)/24 h), and the combination of doxorubicin and paclitaxel (AT, 50 mg/m(2) and 150 mg/m(2)/24 h, plus granulocyte colony-stimulating factor 5 mg/kg) as first-line therapy. Patients receiving single-agent doxorubicin or paclitaxel were crossed over to the other agent at time of progression.

Patients and methods: Patients were well balanced for on-study characteristics.

Results: Responses (complete response and partial response) were seen in 36% of doxorubicin, 34% of paclitaxel, and 47% of AT patients (P =.84 for doxorubicin v paclitaxel, P =.007 for v AT, P =.004 for paclitaxel v AT). Median time to treatment failure (TTF) is 5.8, 6.0, and 8.0 months for doxorubicin, paclitaxel, and AT, respectively (P =.68 for doxorubicin v paclitaxel, P =.003 for doxorubicin v AT, P =.009 for paclitaxel v AT). Median survivals are 18.9 months for patients taking doxorubicin, 22.2 months for patients taking paclitaxel, and 22.0 months for patients taking AT (P = not significant). Responses were seen in 20% of patients crossing from doxorubicin --> paclitaxel and 22% of patients crossing from paclitaxel --> doxorubicin (P = not significant). Changes in global quality-of-life measurements from on-study to week 16 were similar in all three groups.

Conclusion: (1) doxorubicin and paclitaxel, in the doses used here, have equivalent activity; (2) the combination of AT results in superior overall response rates and time to TTF; and (3) despite these results, combination therapy with AT did not improve either survival or quality of life compared to sequential single-agent therapy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / secondary
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Doxorubicin / administration & dosage*
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Humans
  • Middle Aged
  • Paclitaxel / administration & dosage*
  • Quality of Life
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Granulocyte Colony-Stimulating Factor
  • Doxorubicin
  • Paclitaxel