Randomized trial of tamoxifen versus combined tamoxifen and octreotide LAR Therapy in the adjuvant treatment of early-stage breast cancer in postmenopausal women: NCIC CTG MA.14

J Clin Oncol. 2011 Oct 10;29(29):3869-76. doi: 10.1200/JCO.2010.33.7006. Epub 2011 Sep 12.

Abstract

Purpose: Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 (IGF-1) levels. This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence.

Patients and methods: The NCIC CTG MA.14 (NCIC Clinical Trials Group MA.14) trial randomly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily (TAM) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly (TAM-OCT) as adjuvant therapy. The primary end point was event-free survival (EFS). Secondary end points were relapse-free survival (RFS), overall survival (OS), toxicity, and effects of treatment on IGF physiology.

Results: Among 667 women with a median follow-up of 7.9 years, 220 events occurred-108 with TAM-OCT and 112 with TAM. Adjusted hazard ratios (HRs; TAM-OCT to TAM) were 0.93 for EFS (95% CI, 0.71 to 1.22; P = .62), 0.84 for RFS (95% CI, 0.59 to 1.18; P = .31), and 0.97 for OS (95% CI, 0.69 to 1.37; P = .86). Among patients with normal baseline gallbladder imaging, cholecystectomy was required in 23.0% of those receiving TAM-OCT but in only 1.4% of those receiving TAM (P < .001). At 4 months, TAM-OCT had significantly (P < .001) lowered IGF-1, IGF binding protein 3, and C-peptide levels. Older age (P = .02), tumor size (P = .001), nodal status (P = .01), high C-peptide levels (P < .001), and higher body mass index (BMI) in models excluding C-peptide (P < .001) were associated with poorer EFS in multivariate analysis.

Conclusion: Octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • C-Peptide / blood
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Humans
  • Insulin / blood
  • Insulin-Like Growth Factor I / metabolism
  • Middle Aged
  • Octreotide / administration & dosage
  • Octreotide / adverse effects
  • Postmenopause
  • Quality of Life
  • Tamoxifen / administration & dosage
  • Tamoxifen / adverse effects
  • Tamoxifen / therapeutic use*
  • Treatment Outcome
  • Vitamin D / blood

Substances

  • Antineoplastic Agents, Hormonal
  • C-Peptide
  • Insulin
  • Tamoxifen
  • Vitamin D
  • Insulin-Like Growth Factor I
  • Octreotide