Prospects for clinical cancer treatment using interleukin-2.
Even if many of these immunologic approaches to anticancer therapy show the desired effect, with a greater percentage of patients having antitumor responses (hopefully without need for ICU level toxicity), it may be unrealistic to hope that these biological treatments will significantly prolong the survival of most patients with large progressively growing tumors. It is possible that the large, yet finite, number of cells with LAK activity that can be activated endogenously, or infused into a patient, may only be able to destroy a finite number of neoplastic cells. If so, the smaller the number of neoplastic cells at the time of in vivo LAK induction therapy, the more likely the chance for effective eradication of all tumor cells. Experimental animal studies support this postulate (46). Clinical regimens utilizing IL-2 therapy, alone or combined with other agents, with documented immunologic and antitumor activity, will need to be tested in a large number of patients in randomized adjuvant trials. This testing will probably require the involvement of large cooperative oncology trials groups, in order to determine the potential prolongation of survival by any adjuvant IL-2 approach. A vast number of regimens could presently be suggested for combining these separate approaches in groupwide trials (especially when issues of dose, route, and scheduling are considered). Trials in murine models must continue rapidly and be interpreted with caution in generating regimens to be tested clinically. Further treatment improvements, to be identified in Phase I and Phase II clinical trials, are still required to allow large groupwide randomized Phase III trials to test tolerable and effective IL-2-containing regimens likely to significantly prolong survival.
Sondel
P M
PM
Department of Pediatrics, University of Wisconsin Medical School, Madison 53792.
Hank
J A
JA
D003131:Combined Modality Therapy; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2