Regional chemotherapy of neoplastic diseases

Recent developments have made regional chemotherapy a more rational endeavour. The important pharmacokinetic principles have been defined. The increase in regional exposure achieved is a direct function of a drug's total body clearance and is an inverse function of the permeability-area product (defining ease of egress) for third spaces or of the regional arterial blood flow for intraarterial infusion. Agents having appropriate properties are available. For new agents with appropriate pharmacokinetic parameters, regional chemotherapy may provide a means to examine the dose response against measurable tumors in the regions in question. The observation that most tumors are hypervascular may be crucial to the development of selective treatments using microspheres to deliver therapy in direct proportion to the density of the microvasculature. Regionally infused vasoconstrictors (epinephrine, angiotensin) may allow shunting of flow away from normal tissue toward tumor without potentially serious systemic cardiovascular effects. Investigations and applications of regional chemotherapy have been fostered immensely by the reliably and convenience of the Infusaid implantable pump and by implantable injection ports. The problem of systemic failure with regional approaches still remains but is approachable using pharmacologically rational programs aimed at delivering maximal systemic chemotherapy along with regional treatment. In hepatic arterial therapy, in particular, a randomized prospective study is being considered to examine the impact of such combined treatment versus regional therapy alone and versus systemic chemotherapy alone for metastatic colorectal cancer to liver. Thus, the future for regional chemotherapy appears exciting. There are many opportunities to apply therapeutic principles rationally with the potential of significant benefit to many patients.