A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up

Cancer. 2003 Jun 1;97(11):2716-23. doi: 10.1002/cncr.11396.

Abstract

Background: The current study was performed to assess whether sequential potentially noncross-resistant chemotherapy prolongs disease-free survival (DFS) and overall survival (OS) in patients with operable breast carcinoma.

Methods: Seven hundred eighty-nine patients were registered and followed for a median of 10 years. They were treated in two groups. In Group 1, patients age < 50 years or age > 50 years but with either negative or unknown estrogen receptor (ER) status were randomized to receive 6 cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) alone or followed by 4 cycles of methotrexate and vinblastine (MV). In Group 2, patients age > or = 50 years with ER-positive disease were randomized to receive either tamoxifen or combination chemotherapy (FAC + MV) for 10 cycles. Analysis was performed according to allocated treatment (intention to treat), with all randomized patients included.

Results: In Group 1 there were no significant differences with regard to DFS or OS between the two treatment arms. The DFS at 5 years was 0.70 and 0.76, respectively, for FAC compared with FAC+MV (P = 0.26). The OS was similar for both groups (0.84 vs. 0.83). It is interesting to note that there was a statistically nonsignificant trend for improved DFS in the FAC + MV arm for patients who were ER-positive. In Group 2, tamoxifen alone led to more prolonged DFS compared to FAC+MV (0.78 vs. 0.66, respectively) but this did not reach statistical significance (P = 0.28). OS also was associated with a trend (P = 0.86) toward prolonged survival for the tamoxifen arm compared with the FAC+MV arm (0.85 vs. 0.74, respectively).

Conclusions: The results of the current trial concerning sequential adjuvant chemotherapy for operable breast carcinoma, which to our knowledge contains the longest follow-up presented to date, failed to demonstrate any additional benefit from the addition of 4 cycles of MV to 6 cycles of FAC chemotherapy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Methotrexate / administration & dosage
  • Middle Aged
  • Receptors, Estrogen / analysis
  • Tamoxifen / administration & dosage
  • Vinblastine / administration & dosage

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Hormonal
  • Antineoplastic Agents, Phytogenic
  • Receptors, Estrogen
  • Tamoxifen
  • Vinblastine
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate