A randomized controlled trial of octreotide pamoate long-acting release and carboplatin versus carboplatin alone in dogs with naturally occurring osteosarcoma: evaluation of insulin-like growth factor suppression and chemotherapy.
OBJECTIVE
The purpose of this research was to determine whether insulin-like growth factor (IGF) suppression, using a long-acting analogue of somatostatin (OncoLAR, octreotide pamoate long-acting release), will decrease chemotherapy resistance by eliminating an important survival signal to osteosarcoma (OSA) cells in a relevant naturally occurring cancer model. EXPERIMNETAL DESIGN: We conducted a randomized, blinded, placebo-controlled preclinical study in pet dogs with naturally occurring OSA. The study compared primary tumor necrosis and apoptosis, and survival of pet dogs receiving OncoLAR and carboplatin chemotherapy compared with dogs receiving placebo and carboplatin.


RESULTS
Dogs receiving OncoLAR had suppression of serum IGF levels by approximately 43% without toxicity. No differences in primary tumor necrosis, apoptosis, tumor IGF mRNA expression, or survival were seen between the dogs receiving OncoLAR plus chemotherapy compared with OncoLAR alone.


CONCLUSIONS
The suppression of IGF levels by the extent and/or duration achieved in the trial was not sufficient to improve chemotherapy-related antitumor effects in pet dogs with OSA.
Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. khannac@mail.nih.gov
Chand
C
Khanna
Jennifer
J
Prehn
David
D
Hayden
Ryan D
RD
Cassaday
Jana
J
Caylor
Shevin
S
Jacob
Seuli M
SM
Bose
Sung-Hyeok
SH
Hong
Stephen M
SM
Hewitt
Lee J
LJ
Helman
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy*; D016190:Carboplatin / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D005500:Follow-Up Studies; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020714:Maximum Tolerated Dose; D015282:Octreotide / Q000008:administration & dosage; D012516:Osteosarcoma / Q000097:blood / Q000188:drug therapy*; D011897:Random Allocation; D015996:Survival Rate; D016896:Treatment Outcome
D007334:Insulin-Like Growth Factor I; D016190:Carboplatin; D015282:Octreotide