Microencapsulated octreotide pamoate in advanced gastrointestinal and pancreatic cancer: a phase I study.
Fourteen patients suffering from advanced colorectal (n = 7), pancreatic (n = 4) or gastric (n = 3) carcinomas received treatment with microencapsulated 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). Two 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 27-37% 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 secretion 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 fragmentation correlated negatively with alterations in IGF-I and IGF-II (P < 0.05). We conclude that microencapsulated octreotide administered in doses up to 160 mg every 2 weeks is well tolerated and has pronounced effects on several components of the IGF system in plasma. In addition, changes in IGFBP-3 protease activity because of cancer may contribute to alterations in IGF-I and -II, indicating the importance of measuring this parameter in addition to IGFs and IGFBPs when evaluating alterations in IGF-I.
Helle
S I
SI
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Geisler
J
J
Poulsen
J P
JP
Hestdal
K
K
Meadows
K
K
Collins
W
W
Tveit
K M
KM
Holly
J M
JM
Lønning
P E
PE
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D015282:Octreotide / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine
D018931:Antineoplastic Agents, Hormonal; D018969:Insulin-Like Growth Factor Binding Proteins; D009363:Neoplasm Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D015282:Octreotide