Alkylating agents are the most effective drugs to be perfused. They react with DNA, altering the nucleic acid and eventually killing the cell.
Melphalan (L-phenylalanine mustard) has been the drug most extensively used, either alone or in combination. Other drugs—cisplatin, thiotepa, dactinomycin and dacarbazine—are also used, but melphalan has many of the qualities of the ideal agent for isolated limb perfusion. It is the least toxic single drug, with low toxicity to soft tissues and blood vessel linings. It has a short half life (meaning that it disappears quickly) and its action isn't limited to specific phases of the cancer cell's life cycle.
A new agent, tumor necrosis factor (TNF), injures the small blood vessels supplying the cancer. It has produced over 90 percent complete tumor responses against melanoma and some sarcomas when used in the isolated perfusion circuit. TNF is very toxic, and leakage into the general circulation can cause toxic shock syndrome and death. Constant monitoring for leakage with radioisotopes is required.
Whatever anticancer drug is used, its effectiveness is enhanced by two aspects of the perfusion procedure. The use of high oxygen concentrations magnifies the effects of the drugs by sensitizing tumor cells and has a tumor-killing effect of its own. Heat opens the blood vessels so that there is a more even and thorough perfusion.
