Design of combination biotherapy studies: future goals and challenges.
The recent large-scale production of biomodulators, also known as biologic response modifiers, made possible through recombinant DNA technology, offers the potential for significant advances in the treatment of cancer. The antitumor activity of these agents, such as interferons, interleukins, and tumor necrosis factor, have generated enthusiasm for further investigation. In an effort to improve response rates, combinations of these agents both with and without conventional therapies are currently being examined. Clinical trials have been conducted with various therapeutic combinations, including a biomodulator plus chemotherapy, combinations of different biomodulators, a biomodulator with concomitant chemotherapy and radiation, and multiple combinations of chemotherapies and biomodulators. These approaches are promising and some limited successes have been reported; however, the goal of increased anticancer activity without greater toxicities or antagonism between various agents is not always achieved. Synergism among active agents is not necessarily assured and quite unexpected and unpredictable toxicities have been noted. The studies to date suggest that important new therapies will emerge, but many questions have to be answered before the specific roles of these new treatments are defined.
Section of Hematology/Oncology, University of Chicago Medical Center, IL 60637.
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Gilewski
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Golomb
D000970:Antineoplastic Agents / Q000627:therapeutic use; D004274:DNA, Recombinant / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000379:methods / Q000639:trends; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007372:Interferons / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D009369:Neoplasms / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004274:DNA, Recombinant; D007155:Immunologic Factors; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons