The efficacy of
tumor therapy using
polyethylene-glycol-modified interleukin-2 (PEG-IL-2), alone or in combination with
cyclophosphamide, was studied in advanced metastatic disease in the guinea pig. Line 10 (L10)
tumor cells appeared in the axillary lymph node only 7 days after intradermal
tumor-cell inoculation, and lymph-node leukocytes were almost completely replaced by
tumor cells on day 28. Local treatment of the intradermally growing L10 hepatocarcinoma in the guinea pig with a relatively low dose of
PEG-IL-2 resulted in regression of the primary
tumor and prevention of
lymph-node metastases.
Therapy was completely curative (4 out of 5 animals) when started on day 7 or 14 after
tumor-cell inoculation. When started on day 21,
therapy was effective in only some (2 out of 5 cured) of the treated animals. Anti-
tumor effects against the primary
tumor and against
lymph-node metastases were observed only after intratumoral (i.t.) administration of
PEG-IL-2. Injection of the agent into or near
lymph-node metastases in the absence of the primary
tumor had no curative effect. In PBS/BSA-treated control animals the primary
tumor and
metastases grew progressively. In the treatment of far advanced metastatic disease, the combination of i.t. administration of
PEG-IL-2 and i.p. injection of
cyclophosphamide (Cy) resulted in improved anti-tumoral effects (5/5 guinea pigs were cured) when compared with monotherapy using either agent (one and none out of 5 animals cured, respectively). PBS/BSA heated controls showed progressive
tumor-growth. We conclude that large primary
tumors and
lymph-node metastases can be treated effectively with
PEG-IL-2. The i.t. route of administration is of major importance in the treatment of
metastases, since administration of
PEG-IL-2 near or into the lymph node had no
therapeutic effect. Combination of
PEG-IL-2 therapy with systemic
injections of Cy significantly improved the curative effects of the treatment of advanced metastatic
cancer.