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

Abstract

BACKGROUNDLong‐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.METHODSThis 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.RESULTSAt 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%).CONCLUSIONSBecause 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. Cancer 2002;94:299–304. © 2002 American Cancer Society.

Measurement of somatostatin receptor subtype 2 mRNA in breast cancer and corresponding normal tissue.

“…We have already demonstrated, in other human cancer models, that the measurement of sst2 mRNA expression with quantitative PCR appears to be well correlated to the in vitro and in vivo expression of the related protein (Sestini et al 1996, Briganti et al 1997, Casini Raggi et al 2000, 2002. In addition, as recently demonstrated in colon cancer (Casini Raggi et al 2002), we compared the results obtained in tumoral tissues with those obtained in the corresponding unaffected tissues.…”

“…Some of the studies showed a reduction in terms of IGF-I plasma concentrations, but no effects on tumor progression (Manni et al 1989, Vennin et al 1989, O'Byrne et al 1999. Two recent trials (Ingle et al 1999, Bajetta et al 2002 showed that the combination of tamoxifen plus octreotide was substantially as efficacious as tamoxifen alone in the treatment of advanced breast carcinoma. Indeed, in none of the aforementioned studies has the ssts pattern of tumors been investigated, knowledge of which is critical if the therapeutic effects of SS analogs are to be exploited.…”

Novel modalities of somatostatin actions

“…For example, the ability of SRIF to inhibit insulin-like growth factor-I expression and serum levels represents the rationale for its use in an adjuvant therapy for tamoxifen in the treatment of breast cancer (32). However, it should be stressed that the recent clinical trials (phase III) indicated that adding somatostatin analogs to tamoxifen do not increase the therapeutic benefit of tamoxifen in the treatment of advanced breast carcinoma (33). Besides, the capacity of SRIF to inhibit angiogenesis is of potential clinical relevance for the indirect control of tumor cell growth (16, 34).…”

Somatostatin receptor expression in hepatocellular carcinoma: prognostic and therapeutic considerations

“…The large majority of these studies have failed to show a clinically relevant anti-tumour effect, most probably due to the co-existence of other activated pathways driving oncogenesis (Hejna et al 2002, Keskin & Yalcin 2013. The best examples of this failure are two randomised phase II trials investigating SSA therapy in patients with advanced breast cancer, both of which reported no benefit in progression-free survival (PFS) (Ingle et al 1999, Bajetta et al 2002. Similarly, a phase III randomised study in 260 patients with advanced colorectal cancer did not identify a benefit in survival (neither in time to progression nor in overall survival (OS)) in the SSA arm (Goldberg et al 1995).…”