A randomized, multicenter prospective trial assessing long-acting release octreotide pamoate plus tamoxifen as a first line therapy for advanced breast carcinoma.

BACKGROUND: Long-acting release octreotide pamoate (OP-LAR) is a synthetic octapeptide that can be administered monthly and whose activity is similar to that of endogenous somatostatin. In vitro and in vivo data suggest that OP-LAR may act as a growth inhibitor or a modulator of growth stimulatory peptides. The potential mechanisms of action of somatostatin analogues in breast carcinoma include the suppression of insulin-like growth factor-1 (a putative tumor growth factor) and the binding to the somatostatin receptors expressed by breast carcinoma cells in order to induce apoptosis.

METHODS: This Phase III, multicenter, randomized, double-blind, placebo-controlled trial involved 203 patients (13% premenopausal and 87% postmenopausal) with locally recurrent (but unsuitable for local treatment) or metastatic breast carcinoma, 199 of whom were actually treated (99 patients with OP-LAR and 100 patients with placebo). All patients received TAM and were estrogen and/or progesteron receptor positive (receptor positivity was an eligibility criterion), and all had measurable or evaluable disease. Any patients who had received previous chemotherapy not given in an adjuvant or neoadjuvant setting were excluded.

RESULTS: At the time of the interim analysis, the tumor response rates (RR) were 20.2% (9 complete responses [CR] and 11 partial responses [PR]) in the OP-LAR arm and 21% (11 CRs and 10 PRs) in the placebo arm, and the median time to progression (TTP) was 25.0 and 26.9 weeks (P = 0.62), respectively. The adverse events experienced by 10% or more of the patients and attributed to octreotide were gastrointestinal in nature: diarrhea (53%), nausea (16%), and abdominal pain (11%).

CONCLUSIONS: Because of the similar RR and TTP in both arms, the trial was stopped at the interim analysis. The current data confirm there is no indication for adding somatostatin analogues to TAM in advanced breast carcinoma.