Influence of schedule on the therapeutic efficacy of chemoimmunotherapy with doxorubicin and interleukin-2.
Combinations of chemotherapeutic agents with recombinant interleukin-2 are currently under investigation in Phase I/II clinical trials as a possible means of improving response rates for metastatic melanoma, breast cancer, non small cell lung and head/neck carcinomas. As chemotherapy often induces marked immune suppression in vivo, the way in which these agents are combined may be of critical consideration to the therapeutic outcome. Using a rat tumour model, this study aimed to define an optimal schedule for the combined administration of doxorubicin (DOX) with interleukin-2 (IL-2). DOX (4.5 mg/kg bolus i.v.) was administered 24 hours before, during, or 24 hours after, IL-2 immunotherapy (1 x 10(5) Cetus U/rat/day for 5 days continuous i.v. infusion) to WAG rats bearing hind limb solid colonic adenocarcinoma implants. Tumour measurements taken over the 4 weeks study period revealed that there was no significant difference in tumour growth inhibition between the three schedules. Furthermore, DOX invariably caused a marked suppression in the rebound lymphoproliferation after cessation of IL-2 therapy (P less than 0.001). These results demonstrate that the therapeutic efficacy of the DOX/IL-2 combination is not influenced by the schedule for the administration of these agents within the times of administration investigated in this study.
Lumsden
A J
AJ
University Department of Surgery, Royal Perth Hospital, Australia.
Codde
J P
JP
Gray
B N
BN
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D007376:Interleukin-2; D011994:Recombinant Proteins; D004317:Doxorubicin