MICROENCAPSULATED OCTREOTIDE PAMOATE IN ADVANCED GASTROINTESTINAL ANDPANCREATIC-CANCER - A PHASE-I STUDY

Fourteen patients suffering from advanced colorectal (n = 7), pancreat ic (n = 4) or gastric (n = 3) carcinomas received treatment with micro encapsulated octreotide pamoate 90 mg i.m. every 4 weeks (n = 4), 160 mg i.m. every 4 weeks (n = 4) or 160 mg i,m, every 2 weeks (n = 6). Tw o patients had stable disease, one for 4 and one for 6 months. Plasma insulin-like growth factor (IGF)-I decreased by 49-53%, IGF-II by 27-3 7% and total IGF-binding protein (IGFBP)-3 by 16-19%, whereas IGFBP-1 increased by 35-55%. Insulin and C-peptide levels decreased by 29-38% and 41-46% respectively. A non-significant decrease in urinary GH secr etion and an increase in the ratio of fragmented to intact IGFBP-3 as well as IGFBP-3 protease activity was seen. The increase in IGFBP-3 fr agmentation correlated negatively with alterations in IGF-I and IGF-II (P < 0.05). We conclude that microencapsulated octreotide administere d in doses up to 160 mg every 2 weeks is well tolerated and has pronou nced effects on several components of the IGF system in plasma. In add ition, changes in IGFBP-3 protease activity because of cancer may cont ribute to alterations in IGF-I and -II, indicating the importance of m easuring this parameter in addition to IGFs and IGFBPs when evaluating alterations in IGF-I.