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PEG‐IL‐2 therapy of advanced cancer in the guinea pig. Impact of the primary tumor and beneficial effect of cyclopphosphamide
Author(s) -
Balemans Lianne T. M.,
Steerenberg Peter A.,
Koppenhagen Frank J.,
Kremer Bas H. A.,
De Mulder Pieter H. M.,
Claessen Anke M. E.,
Scheper Rik J.,
Otter Willem Den
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580621
Subject(s) - medicine , cyclophosphamide , lymph node , primary tumor , lymph , peg ratio , intradermal injection , chemotherapy , metastasis , cancer , pathology , immunology , finance , economics
The efficacy of tumor therapy using polyethylene‐glycolmodified 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.