Combination Chemotherapy

The value of combination chemotherapy has been proved in humans. The combined use of two or more drugs often is superior to single-agent treatment in many cancers, and certain principles have been used in designing such treatments:

1. Each drug used in the combination regimen should have some individual therapeutic activity against the particular tumor being treated. A drug that is not active against a tumor when used as a single agent is likely to increase tox-icity without increasing the therapeutic efficacy of a combined drug regimen.

2. Drugs that act by different mechanisms may have additive or synergistic therapeutic effects. Tumors may contain heterogeneous clones of cells that differ in their susceptibility to drugs. Combination therapy will thus increase log cell kill and diminish the probability of emergence of resistant clones of tumor cells.

3. Drugs with different dose-limiting toxicities should be used to avoid cumulative damage to a single organ.

4. Intensive intermittent schedules of drug treatment should allow time for recovery from the acute toxic effects of antineoplastic agents, primarily bone marrow toxicity. The use of non-myelosuppressive agents can be considered during the recovery period, especially for treatment of fast-growing cancers.

5. Several cycles of treatment should be given, since one or two cycles of therapy are rarely sufficient to eradicate a tumor. Most curable tumors require at least six to eight cycles of therapy.

The chemotherapy of advanced Hodgkin's disease is one of the best examples of successful combination chemotherapy. Combination therapy with the MOPP regimen (mechlorethamine, Oncovin [vincristine sulfate], procarbazine, prednisone), alternating with ABVD (Adriamycin [doxorubicin hydrochloride], bleomycin, vinblastine, dacarbazine), has resulted in cure rates of 50 to 60%.

The treatment of Hodgkin's disease also illustrates the use of combined modalities, that is, radiation plus chemotherapy. The combined modality approach to several childhood tumors (e.g.,Ewing's sarcoma,Wilms' tumor, and rhabdomyosarcoma) has dramatically increased the cure rates for these diseases.

Adjuvant chemotherapy involves the use of antineo-plastic drugs when surgery or radiation therapy has eradicated the primary tumor but historical experience with similar patients indicates a high risk of relapse due to micrometastases. Adjuvant chemotherapy should employ drugs that are known to be effective in the treatment of advanced stages of the particular tumor being treated. Adjuvant chemotherapy has played a major role in the cure of several types of childhood cancers as well as breast cancer, colorectal cancer, and osteosar-coma in adults.

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