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

• Published in: British journal of cancer Vol. 79; no. 9-10; pp. 1413 - 1418
• Main Authors: O'BYRNE, K. J, DOBBS, N, PROPPER, D. J, BRAYBROOKE, J. P, KOUKOURAKIS, M. I, MITCHELL, K, WOODHULL, J, TALBOT, D. C, SCHALLY, A. V, HARRIS, A. L
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-03-1999
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Biological and medical sciences; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Chemotherapy; Disease Progression; Female; Humans; Insulin-Like Growth Factor I - metabolism; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Prolactin - blood; Regular; Somatostatin - administration & dosage; Somatostatin - adverse effects; Somatostatin - analogs & derivatives; Antineoplastic agent; Human; Peptides; Peptide hormone; Metastasis; Malignant tumor; Insulin like growth factor 1; Biological activity; Mammary gland diseases; Protein hormone; Chemotherapy; Treatment; Adenohypophyseal hormone; Prolactin; Analog; Phase II trial; Mammary gland; Somatostatin; Vapreotide
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6690226

RC-160 (octastatin/vapreotide) is a potent octapeptide analogue of somatostatin with growth inhibitory activity in experimental tumours in vitro and in 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) for weeks 2-4 and subsequently 6 mg day(-1) until the end of treatment, administered by continuous subcutaneous infusion in the management of 14 women with previously treated metastatic breast cancer. The age range was 37-80 years (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 toxicities were seen. Abscess formation developed at the infusion site in eight patients and erythema and discomfort was seen in a further three patients. A significant reduction in IGF-I levels occurred by day 7 and was maintained throughout 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 three patients fell to within the normal range 7 days after commencing RC-160 treatment. 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 objective tumour responses were observed, all patients showing disease progression within 3 months of commencing treatment. These findings demonstrate that high-dose RC-160, administered as a continuous subcutaneous infusion, can reduce serum levels of the breast growth factors IGF-I and prolactin but is ineffective in the management of metastatic breast cancer. Encouraging preclinical anti-tumour activity and the favourable toxicity profile in patients suggest the merit of future studies combining RC-160 with anti-oestrogen, cytotoxic and anti-angiogenic agents.