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 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.
O'Byrne
K J
KJ
Imperial Cancer Research Fund Medical Oncology Unit, Churchill Hospital, Oxford, UK.
Dobbs
N
N
Propper
D J
DJ
Braybrooke
J P
JP
Koukourakis
M I
MI
Mitchell
K
K
Woodhull
J
J
Talbot
D C
DC
Schally
A V
AV
Harris
A L
AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011388:Prolactin / Q000097:blood; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D000970:Antineoplastic Agents; C051458:vapreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D011388:Prolactin