ABSTRACT
Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-ß-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age- and sex-matched controls treated with paclitaxel and low-dose aspirin. By a cumulative dose of 1,500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% confidence interval, 0.9-3.0). Among those receiving a high-dose paclitaxel regimen, the hazard ratio was 2.3 (95% confidence interval, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy in patients treated with high-dose paclitaxel.
Subject(s)
Cytochrome P-450 CYP2C8/metabolism , Paclitaxel/administration & dosage , Peripheral Nervous System Diseases/chemically induced , Platelet Aggregation Inhibitors/administration & dosage , Ticlopidine/analogs & derivatives , Aged , Aspirin/administration & dosage , Clopidogrel , Dose-Response Relationship, Drug , Drug Interactions , Female , Humans , Liver/metabolism , Male , Middle Aged , Paclitaxel/adverse effects , Paclitaxel/pharmacokinetics , Peripheral Nervous System Diseases/epidemiology , Pharmacoepidemiology , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/pharmacokinetics , Retrospective Studies , Severity of Illness Index , Ticlopidine/administration & dosage , Ticlopidine/adverse effects , Ticlopidine/pharmacokineticsABSTRACT
BACKGROUND: Aims of this study were to describe the prevalence of comorbidity in newly diagnosed elderly cancer cases compared with the background population and to describe its influence on overall and cancer mortality. METHODS: Population-based study of all 70+ year-olds in a Danish province diagnosed with breast, lung, colorectal, prostate, or ovarian cancer from 1 January 1996 to 31 December 2006. Comorbidity was measured according to Charlson's comorbidity index (CCI). Prevalence of comorbidity in newly diagnosed cancer patients was compared with a control group by conditional logistic regression, and influence of comorbidity on mortality was analysed by Cox proportional hazards method. RESULTS: A total of 6325 incident cancer cases were identified. Elderly lung and colorectal cancer patients had significantly more comorbidity than the background population. Severe comorbidity was associated with higher overall mortality in the lung, colorectal, and prostate cancer patients, hazard ratios 1.51 (95% CI 1.24-1.83), 1.41 (95% CI 1.14-1.73), and 2.14 (95% CI 1.65-2.77), respectively. Comorbidity did not affect cancer-specific mortality in general. CONCLUSION: Colorectal and lung cancer was associated with increased comorbidity burden in the elderly compared with the background population. Comorbidity was associated with increased overall mortality in elderly cancer patients but not consistently with cancer-specific mortality.
