Spherex (degradable starch microspheres) chemo-occlusion--enhancement of tumor drug concentration and therapeutic efficacy: an overview.
The efficacy of systemic chemotherapy in the treatment of primary and secondary liver cancer is poor. Intra-arterial delivery of fluoropyrimidines resulted in a significantly higher tumor response, but survival was prolonged by only a few months. Obviously, there is still a great need for improved therapeutic strategies. As the regional blood flow is of importance for the advantage of intra-arterial administration of cytotoxic drugs, degradable starch microspheres (DSMs) have been developed specifically to achieve temporary vascular occlusion during coadministration of cytotoxic drugs. Peak plasma concentrations, as well as the area under the concentration-time curve (AUC) of mitomycin C in plasma have been found to be significantly reduced following intra-arterial coadministration with DSMs. Similar results were also obtained with other drugs, such as nitrosoureas, doxorubicin, and 5-fluorouracil. The temporary vascular occlusion induced by DSMs enables a coadministered drug to be lodged in the target area for a prolonged period of time, resulting in a selectively increased uptake of labeled low molecular weight markers and several cytotoxic drugs into liver tumors compared with normal liver tissue. Vascular occlusion induced by DSMs has been demonstrated to redistribute the blood flow to hypovascular areas, which might be of particular importance for improving the efficacy of intra-arterial chemotherapy of hypovascular liver tumors. Passage through arteriovenous shunts was generally increased after DSM injection. However, this was without clinical significance as respiratory distress symptoms were found in only 1% of the sessions and were not considered to be serious in any of these patients. To take advantage of the pharmacokinetic modulation of coinjected drugs and, in addition, the redistribution of blood flow to hypovascular tumor areas, the goal is to achieve an almost complete vascular occlusion by injection of DSMs. Therefore, due to the wide variation between patients in the size and vascularity of liver tumors, the dose of DSMs has to be individualized. Degradable starch microspheres have been shown to enhance the antitumor efficacy of several cytotoxic drugs in animal experimental models and in noncomparative and randomized clinical studies.
Håkansson
L
L
Department of Oncology, University Hospital, Linköping, Sweden.
Håkansson
A
A
Morales
O
O
Thorelius
L
L
Warfving
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001673:Biodegradation, Environmental; D006801:Humans; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000098:blood supply / Q000628:therapy*; D008863:Microspheres; D012039:Regional Blood Flow; D013213:Starch / Q000008:administration & dosage*
D000970:Antineoplastic Agents; C044817:Spherex; D013213:Starch