A randomized trial of tamoxifen alone or combined with octreotide in the treatment of women with metastatic breast carcinoma

BAGKGROUND. Tamoxifen (TAM) is generally considered the hormonal agent of c hoice for postmenopausal women with hormone receptor positive breast carcin oma. The somatostatin analogues, including octreotide, have demonstrated in hibition of breast carcinoma cell lines and multiple endocrinologic actions , including reduction of insulin-like growth factor I (IGF-I), a potent mit ogen for breast carcinoma cells. In an attempt to improve the efficacy of T AM, this randomized trial was performed. METHODS. One hundred thirty-five eligible postmenopausal women with metasta tic breast carcinoma were randomized to TAM (10 mg twice daily) alone or co mbined with octreotide 150 mu g (administered subcutaneously thrice daily). The two groups were well balanced, except the TAM group had higher proport ions of patients with visceral disease (50% vs. 37%) and a disease free int erval longer than 5 years (47% vs. 34%). A cohort of Is patients was evalua ted for the impact of treatment on serum IGF-I, free IGF-I, IGF binding pro tein 3 levels, and total IGF binding capacity. RESULTS. The median time to progression was estimated to be 14.2 months wit h TAM and 10.3 months with TAM plus octreotide. The distribution of progres sion free survival times revealed no significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM + octreotide) was 0.81 (95% confiden ce interval [CI], 0.56-1.17). The distribution of survival times revealed n o significant difference (P = 0.92), and the death hazard ratio was 0.98 (9 5% CI, 0.62-1.55). When the 106 patients with measurable or evaluable disea se were considered, the objective response rate was 49% with TAM alone and 43% with TAM plus octreotide (P = 0.70). Patients who received TAM plus oct reotide had higher incidences of nausea, diarrhea, and steatorrhea. The per centage of decline in serum IGF-I, from pretreatment levels to those follow ing 3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM p lus octreotide than with TAM alone. CONCLUSIONS. There is no indication that the combination of TAM plus octreo tide as administered in this study is substantially more efficacious than T AM alone in the treatment of postmenopausal women with metastatic breast ca rcinoma. The limited cohort included in IGF-I studies suggests that TAM plu s octreotide produces a significantly greater reduction in serum IGF-I leve ls. Cancer 1999;85: 1284-92. (C) 1999 American Cancer Society.