Use of an artificial lymphatic system during carboplatin infusion to improve canine osteosarcoma blood flow and clinical response.
BACKGROUND
The artificial lymphatic system (ALS), a mechanical system designed to reduce increased interstitial fluid pressure in solid tumors and enhance the delivery of chemotherapy, was evaluated within a randomized clinical trial treating spontaneously occurring canine appendicular osteosarcoma (OS), a tumor similar to its human OS counterpart.


METHODS
An ALS was investigated for its ability to increase OS blood flow and increase uptake of intravenously administered carboplatin.


RESULTS
Blood flow increased by 314% in tumors with active ALS drains versus 126% in control tumors (P < .03). Tumor carboplatin uptake increased by 51% after drain activation (P = .07). Microvascular density (MVD) was measured in tumors after surgical amputation and in corresponding bone regions in a cohort of normal dogs. The OS tumors had equivalent MVD as normal bone, and MVD was higher in the humerus than the femur (P < .03) in both tumor and normal bone. Median survival between the ALS-treated and control cohorts was not different despite increased drug uptake or ALS manipulation. Compared with historic controls, ALS drain insertion into tumors to reduce interstitial fluid pressure did not worsen the prognosis.


CONCLUSIONS
The findings in canine spontaneously occurring OS indicate that an ALS may be of value as a chemotherapy adjunct for enhancing the delivery of chemotherapy to tumor interstitium.
DiResta
Gene R
GR
Orthopaedic Surgical Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021-6007, USA. direstag@mskcc.org
Aiken
Sean W
SW
Brown
Holly K
HK
Bergman
Philip J
PJ
Hohenhaus
Ann
A
Ehrhart
E J
EJ
Baer
Keith
K
Healey
John H
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001187:Artificial Organs; D001706:Biopsy; D001859:Bone Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000662:veterinary*; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015331:Cohort Studies; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D005260:Female; D005269:Femur; D006811:Humerus; D007262:Infusions, Intravenous; D008208:Lymphatic System; D008297:Male; D012516:Osteosarcoma / Q000098:blood supply* / Q000188:drug therapy* / Q000662:veterinary*; D010100:Oxygen / Q000378:metabolism; D012039:Regional Blood Flow; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016190:Carboplatin; D010100:Oxygen