Use of an Artificial Lymphatic System During Carboplatin Infusion to Improve Canine Osteosarcoma Blood Flow and Clinical Response
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.
An ALS was investigated for its ability to increase OS blood flow and increase uptake of intravenously administered carboplatin.
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.
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.
KeywordsOsteosarcoma Carboplatin Blood flow Interstitial fluid pressure Microvessel density Canine Artificial lymphatic system
- 5.Arbit E, Lee J, DiResta GR. 1994; Interstitial hypertension in human brain tumors: possible role in peritumoral edema formation. In: Nagai H, Kamiya K, Ishii S, eds. Intracranial Pressure. Nagoya, Japan: Springer-Verlag, 610–4Google Scholar
- 6.Healey JH and DiResta GR. Measurement of interstitial fluid pressure and blood flow in human bone tumors and adjacent normal tissue. Paper presented at: Orthopedic Research Society, 44th Annual Meeting; March 16–19, 1998; New Orleans, LAGoogle Scholar
- 10.Process and device to reduce interstitial fluid pressure in tissue. US patents 5,484,399, 16 January 1996, 6,547,777, 15 April 2003Google Scholar
- 14.Zachos TA, Chiaramonte D, DiResta GR, et al. Canine osteosarcoma: treatment with surgery, chemotherapy and/or radiation therapy, The Animal Medical Center, 1993–1998. Proceedings, 19th Annual Veterinary Cancer Society Conference. November 13–19, 1999, Wood’s Hole, MAGoogle Scholar
- 22.Evans HE, ed. Miller’s Anatomy of Dog. 3rd ed. Philadelphia: WB Saunders, 1993Google Scholar
- 29.Barbareschi M, Weidner N, Gasparini G, et al. Microvessel density quantification in breast carcinomas. Appl Immunohistochem 1995; 3:75–84Google Scholar