Purpose Potential cytochrome P-450 (CYP) drug-drug interactions in adults with metastatic

Purpose Potential cytochrome P-450 (CYP) drug-drug interactions in adults with metastatic sound tumors and their effect on eligibility for Phase I clinical trials were characterized. from 1773 patients were Ombrabulin analyzed: 1489 were not enrolled in a Phase I trial and 284 were enrolled in a Phase I trial. Polypharmacy was significantly more prevalent in the group enrolled in a Phase I trial compared with those not enrolled (95% versus 80% < 0.001). The majority of patients not enrolled in a Phase I trial were taking at least one CYP isozyme inhibitor (87%) and at least one CYP isozyme inducer (45%). In a separate analysis four Phase I trials were evaluated. Of 295 screened patients 3.2% could not enroll due to concurrent medications. Charts from 74 enrolled patients revealed 655 concurrent medications-93 medications required further review for eligibility involving 51 (69%) of patients. Of the 93 medications 38 (41%) were stopped and 41 (44%) were changed for the study. Conclusion Polypharmacy and the use of medications that interact with CYP isoyzmes were common in adult patients with metastatic solid tumors. Patients enrolling in Phase I studies often require medication changes to meet eligibility requirements. In recent decades advances in the management of many chronic diseases have resulted in increased long-term medication use. The use of five or more medications by a patient has become more common in the general populace.1 2 The taking of multiple medications or poly-pharmacy is even more prevalent in patients with Ombrabulin cancer because of frequent preexisting comorbidities as well as the use of medications to manage malignancy symptoms.3 4 Poly-pharmacy is associated with multiple unfavorable clinical outcomes ranging from hospitalization to death.5-8 Over the past decade multiple new anticancer brokers have become available. Many of these are continuously administered oral drugs thereby increasing the potential for unfavorable Rabbit Polyclonal to PPP4R2. outcomes due to pharmacokinetic drug-drug interactions (DDIs) in oncology patients.9-11 Cytochrome P-450 (CYP) isozymes catalyze the biotransformation of chemicals and play a role in the metabolism of many oral medications.12 13 Medications may inhibit or induce the activity of one or more CYP isozymes and thereby interfere with the metabolism of a medication (substrate) by these isozymes.14 Concurrent use of an inducing medication and a substrate leads to decreased plasma concentrations of the substrate medication. This could lead to a subsequent loss of effectiveness. In contrast concurrent use of an inhibiting medication with a substrate can lead to increased substrate concentrations and possible toxicity. The therapeutic range of most oncology brokers is narrow. Thus minor alterations in the concentrations of anti-cancer drugs may significantly affect the drugs’ activity toxicity or both. Many examples of pharmacokinetic DDIs resulting in either decreased effectiveness or increased adverse events with oncological drugs have been reported.10 15 Studies regarding the frequency of actual or potential DDIs in oncology patients are limited; however the existing literature suggests that 30-46% of oncology patients are Ombrabulin at risk.18-20 The patient populations in these studies combined solid and hematologic malignancies being treated Ombrabulin for palliative or curative intent. This heterogeneity limits the extent to which the results can be applied to patients with metastatic solid tumors. Treatment for this populace is usually heavily dependent on systemic therapies rather than local therapies. Furthermore medications for symptom management are common in patients with metastatic cancer. The medical literature describes only the concurrent use of medications with known DDIs rather than reporting the use of medications with significant potential for pharmacokinetic interactions. This leaves a gap in the current knowledge regarding the risk of DDIs in patients with metastatic solid tumors for whom a new anticancer agent is being considered. Potential DDIs are also very important to consider for patients participating in Phase I studies. Although these studies are necessary for drug development the drugs often have a narrow therapeutic range and investigators’ understanding of the toxicities of the study agents is inherently limited.21 This increases the potential risk for harm from a DDI. Our experience has suggested that polypharmacy and the use of medications that interact with CYP isozymes are very common in patients enrolled in Phase I studies. Medication dosages have frequently been adjusted based on.