Phase II study of RC-160 (vapreotide), an octapeptide analogue of somatostatin, in the treatment of metastatic breast cancer

RC-160 (octastatin/vapreotide) is a potent octapeptide analogue of somatost atin with growth inhibitory activity in experimental tumours in vitro and i n vivo, including breast cancer. We evaluated the efficacy and tolerability of high-dose RC-160, 3 mg day(-1) on week 1 increased to 4.5 mg day(-1) fo r weeks 2-4 and subsequently 6 mg day(-1) until the end of treatment, admin istered by continuous subcutaneous infusion in the management of 14 women w ith previously treated metastatic breast cancer. The age range was 37-80 ye ars (median 58.5 years) and performance status 0-2. The treatment was well tolerated with no dose reductions being required. No grade 3 or 4 toxicitie s were seen. Abscess formation developed at the infusion site in eight pati ents and erythema and discomfort was seen in a further three patients. A si gnificant reduction in IGF-I levels occurred by day 7 and was maintained th roughout the treatment. The lowest dose of RC-160 produced the maximal IGF- I response. Although there was no reduction in prolactin levels in patients whose baseline levels were normal, elevated prolactin levels found in thre e patients fell to within the normal range 7 days after commencing RC-160 t reatment. A small but significant rise in fasting blood glucose levels was also recorded, the highest level on treatment being 7.6 mmol l(-1). No obje ctive tumour responses were observed, all patients showing disease progress ion within 3 months of commencing treatment. These findings demonstrate tha t high-dose RC-160, administered as a continuous subcutaneous infusion, can reduce serum levels of the breast growth factors IGF-I and prolactin but i s ineffective in the management of metastatic breast cancer. Encouraging pr eclinical anti-tumour activity and the favourable toxicity profile in patie nts suggest the merit of future studies combining RC-160 with anti-oestroge n, cytotoxic and anti-angiogenic agents.