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:
·
Each drug used in the combination regimen should have some individual therapeutic activ-ity 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 effi-cacy of a
combined drug regimen.
·
Drugs that act by different
mechanisms may have additive or synergistic therapeutic ef-fects. Tumors
may contain heterogeneous clones of cells that differ in their susceptibility
to drugs. Combination therapy will thus in-crease log cell kill and diminish
the probability of emergence of resistant clones of tumor cells.
·
Drugs with different
dose-limiting toxicities should be used to avoid cumulative damage to a
single organ.
·
Intensive intermittent
schedules of drug treat-ment should allow time for recovery from the acute
toxic effects of antineoplastic agents, pri-marily bone marrow toxicity. The
use of non-myelosuppressive agents can be considered during the recovery
period, especially for treatment of fast-growing cancers.
·
Several cycles of treatment
should be given, since one or two cycles of therapy are rarely sufficient to
eradicate a tumor. Most curable tumors
re-quire 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 sul-fate],
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
in-creased 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 ma-jor 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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