Modulation of hematologic and immunologic effects of high dose chemotherapy by interleukin-2 in a murine tumor model.
To determine if intensive chemotherapy consisting of cyclophosphamide (C), etoposide (E), and cisplatin (P) (CEP) may be usefully combined with recombinant human interleukin-2 (rhIL-2), we examined a murine tumor model designed to approximate a common clinical situation: macroscopic, drug-resistant cancer. Using C57BL/6 mice with extensive tumor burden 10 days after intravenous B16 melanoma cell injection, we observed (1) C, E, and P synergize to enhance survival but do not cure mice at the highest tolerable dose (C = 200 mg/kg, E = 60 mg/kg, and P = 3 mg/kg); (2) rhIL-2 at 3 x 10(5) U (subcutaneously) daily for 4 days administered 10-18 days after B16 injection significantly improves survival; (3) CEP plus rhIL-2 is more effective than CEP alone only when rhIL-2 is administered before CEP; (4) CEP suppresses IL-2-induced lymphokine-activated killer cell activity in the spleen; and (5) rhIL-2 protects mice incompletely from the immunologic and hematologic suppression of CEP. Our results suggest that intensive chemotherapy combined with rhIL-2 may be beneficial. The success of any such combination may be schedule dependent.
Rinehart
J J
JJ
Division of Hematology and Oncology, Texas A&M University College of Medicine, Temple 76508.
Triozzi
P L
PL
Lee
M H
MH
Aldrich
W
W
Young
D
D
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL
D007376:Interleukin-2; D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin