Comprehensive Nursing Pharmacology Q 239
Combination chemotherapy is used in the treatment of cancer because:
A. Single-agent therapy produces cell lines that are resistant.
B. Two drugs are more likely to work.
C. Single-agent therapy requires larger doses for long remissions.
D. Two cancers may be present.
Correct Answer: A. Single-agent therapy produces cell lines that are resistant.
Single-agent therapy tends to produce resistant tumor cells, making remission or cure impossible. The most compelling rationale for combination chemotherapy is (1) tumor cell heterogeneity and its implication for drug resistance, and (2) the success of combination chemotherapy in the clinic.
Option B: Current studies have demonstrated evidence for synergy or an additive effect between established chemotherapeutic agents and agents representing other classes. Tamoxifen, when used in combination, is additive and sometimes synergistic. Herceptin, a monoclonal antibody to her 2/neu is synergistic with doxorubicin and paclitaxel. Her 2/neu (erbB2) is present on the cancer cell surface of 25% of the patients with breast cancer.
Option C: The addition of a complement-fixing monoclonal antibody, rituximab, to cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone (CHOP) chemotherapy in non-Hodgkin’s lymphoma increases response without an increase in toxicity. Vincristine and prednisone represent a long-established combination that is highly potent for ALL. All-trans-retinoic acid (ATRA) and arsenic trioxide interact with acute progranulocytic leukemia cells with resultant differentiation and remission.
Option D: While tumors are clonal in origin, the increasing DNA instability that accompanies the onset of neoplasia leads to an increased variation of daughter cells, referred to as clonal evolution to tumor cell heterogeneity. This is associated with the selection for progeny with greater survival capacity, evident as a higher proliferative capacity, resistance to apoptosis, greater metastatic or invasive potential, reduced dependence on normal cellular growth factors, and angiogenesis.