Concomitant medications, aging-related changes in drug distribution may be predictors of chemotherapy adverse events in elderly patients with cancer

June 1, 2008

Drug-drug and disease-drug interactions in elderly patients with cancer are significant; 33% of elderly patients who are taking 3 or more medications are rehospitalized within 6 months of a hospital discharge. "A better index of predicting tolerance to chemotherapy in the elderly is crucial," said Mihaela Popa, MD, Moffitt Cancer Center, Tampa, Florida. Tolerance to chemotherapy among older patients with cancer may be affected by multiple chronic conditions requiring multiple medications and aging-related alterations that induce changes in drug distribution, she said.

Drug-drug and disease-drug interactions in elderly patients with cancer are significant; 33% of elderly patients who are taking 3 or more medications are rehospitalized within 6 months of a hospital discharge. "A better index of predicting tolerance to chemotherapy in the elderly is crucial," said Mihaela Popa, MD, Moffitt Cancer Center, Tampa, Florida. Tolerance to chemotherapy among older patients with cancer may be affected by multiple chronic conditions requiring multiple medications and aging-related alterations that induce changes in drug distribution, she said.

The results of a study conducted by Dr Popa demonstrated that both cytochrome p450 inhibition and protein-binding characteristics of various drugs can influence chemotherapy effects in the elderly; the study also demonstrated potential predictors of chemotherapy adverse events in this patient population.

Researchers retrospectively analyzed the records of 284 patients with cancer who were aged 70 years or older and who were receiving chemotherapy in the Senior Adult Oncology Program at Moffitt Cancer Center. Severe hematologic side effects from chemotherapy, such as decreased white blood cell count, were more likely to occur in patients taking agents that interfere with protein binding, such as amlodipine, celecoxib, and omeprazole (p = .003). Other predictors of severe hematologic side effects were bone marrow invasion (p = .027), tumor stage (p = .005), mean plasma bilirubin (p=.025), and mean red blood cell count during chemotherapy (p = .012).

Moderate-to-severe nonhematologic chemotherapy adverse events such as fatigue and diarrhea were predicted by concomitant treatment with drugs inhibiting cytochrome p450 enzymes, such as ketoconazole and amiodarone. In addition, a higher body mass index predicted moderate-to-severe hematologic side effects (p = .048), as did liver function before chemotherapy initiation (p = .018). The intrinsic toxicity of the chemotherapy regimen used also affected the occurrence of adverse events.

"The 2-drug interaction mechanism we studied, p450 inhibition and protein binding, work in concert," Dr Popa said. "The drugs older cancer patients take might influence the side effects from chemotherapy and research on the influence of drug interactions on chemotherapy tolerance should account for both p450 and protein binding interactions."