Prior to the 1970s, therapeutic regimens for oncology consisted largely of surgery, radiation, and the use of non-specific, combination chemotherapy. Working in cooperative groups organized through the National Institutes of Health’s National Cancer Institute, oncologists sought to refine combination regimens for both hematological malignancies and solid tumors. By the 1970s and 1980s, these same oncologists had optimized empiric combinations, offering clinically beneficial and cost-effective cancer treatment in many hematological indications. Multi-drug regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), introduced in the late 1980s, induced 45%-55% complete remissions and 30%-35% cures in non-Hodgkin patients, while refinements to treatment protocols for Hodgkin lymphoma resulted in more dramatic cure rates around 70%. Although these accomplishments are impressive, therapeutic advances have been more muted in solid tumors. Relative success stories like the use of tamoxifen to treat estrogen-responsive breast cancer have been outweighed by the lack of progress against lung and colorectal cancer.
Next-Generation Combination Therapy In Oncology
Despite significant scientific advances tied to the molecular understanding of cancer, clinical advances have been more limited, largely because the complexity of most tumors defies novel single-target approaches. Clinical advances in the future will require developing rational combinations of targeted therapeutics, as well as leveraging advances in biomarkers and clinical trial design. Vetting new targets with a biomarker, pursuing them in combination trials with several targeted agents, and efficiently moving the resulting rational combination through development to regulatory approval will be the roadmap for commercial success.
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