Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy

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Abstract

Purpose

Increased risk of drug interactions due to polypharmacy and aging-related changes in physiology among older patients with cancer is further augmented during chemotherapy. No previous studies examined potential drug interactions (PDIs) from polypharmacy and their association with chemotherapy tolerance in older patients with cancer.

Methods

This study is a retrospective medical chart review of 244 patients aged 70 + years who received chemotherapy for solid or hematological malignancies. PDI among all drugs, supplements, and herbals taken with the first chemotherapy cycle were screened for using the Drug Interaction Facts software, which classifies PDIs into five levels of clinical significance with level 1 being the highest. Descriptive and correlative statistics were used to describe rates of PDI. The association between PDI and severe chemotoxicity was tested with logistic regressions adjusted for baseline covariates.

Results

A total of 769 PDIs were identified in 75.4% patients. Of the 82 level 1 PDIs identified among these, 32 PDIs involved chemotherapeutics. A large proportion of the identified PDIs were of minor clinical significance. The risk of severe non-hematological toxicity almost doubled with each level 1 PDI (OR = 1.94, 95% CI: 1.22-3.09), and tripled with each level 1 PDI involving chemotherapeutics (OR = 3.08, 95% CI: 1.33-7.12). No association between PDI and hematological toxicity was found.

Conclusions

In this convenience sample of older patients with cancer receiving chemotherapy we found notable rates of PDI and a substantial adjusted impact of PDI on risk of non-hematological toxicity. These findings warrant further research to optimize chemotherapy outcomes.

Introduction

Increasing age and polypharmacy are associated for a number of reasons. These include: increased prevalence of multimorbidity;[1], [2], [3], [4], [5], [6] absence of a primary care provider able to coordinate the care of different specialists;[7], [8] and increased use of alternative forms of treatments.9 Also older individuals may keep taking medications they no longer need when multiple physicians and multiple sites of care are involved.8

Information related to polypharmacy in older patients with cancer is limited.10 Six studies[5], [11], [12], [13], [14], [15] were conducted in ambulatory and three[16], [17], [18] in hospitalized patients with cancer. All studies revealed high prevalence of polypharmacy, and its associated risk of drug interactions. The risk of interaction ranged from 29 to 58%,[13], [15], [16] and in two studies[16], [17] the risk of inappropriate prescriptions varied between 29 and 41%. None of the studies assessed the clinical consequences of polypharmacy. In our program, older patients take an average of 6 medications, 2 of them being metabolized by p450, a key player (although not the only one) in drug interactions.19

In the present study we investigated the prevalence and severity of drug–drug interactions in older patients with cancer receiving chemotherapy, the association between drug interactions and chemotherapy-related toxicity, and the correlation between the risk of drug-drug interactions and the number of medications taken by each patient. The Senior Adult Oncology Program (SAOP) at the Moffitt Cancer Center in Tampa represents a suitable setting for this research. Established in 1993 for the management of patients with cancer aged 70 and over, the SAOP collects comprehensive baseline information, including a geriatric screening and a record of all medications the patients take at initial presentation, using self reports, brown bag approach, and previous medical records. It updates the medication list at each subsequent visit.

Section snippets

Study Design and Participants

This is a retrospective medical record review of patients with cancer aged ≥ 70 years who received chemotherapy in the SAOP in 1995–2005. This study was approved by the Institutional Review Board at the University of South Florida. It uses a cohort that we created to study the impact of p450 interactions on tolerance of chemotherapy in the elderly.19 We reviewed the records of all patients who received regimens including at least one chemotherapeutic agent metabolized by the cytochrome p450 (CYP)

Epidemiology

The sample characteristics are presented in Table 2. Sixty-six patients (27%) experienced a G4 hematological toxicity; 126 patients (51.6%) experienced grades 3–4 non-hematological toxicity; among them, 40 (16.4%) experienced both types of toxicity.

At the time of chemotherapy initiation, patients in our sample reported taking a mean of 11.7 ± 4.6 drugs (range 3–41), including prescription chemotherapy and non-chemotherapy drugs, over the counter drugs, herbals, and supplements. We identified 769

Prevalence

Our study confirms the high number of medications taken by patients with cancer, with the resulting PDI, and provides data more specific to patients above the age of 70. This is the first study to establish the incidence and severity of PDIs and their association with severe chemotherapy adverse events in these patients.

In comparison with studies in general outpatient oncologic populations, our proportion of patients presenting PDIs is higher: Riechelmann et al. report a proportion of 27%, and

Conclusions

In conclusion, in a sample of cancer patients aged ≥ 70 years we found notable rates of PDI and a substantial association between high-level PDI and risk of non-hematological toxicity from chemotherapy. This is a call for oncologists to carefully review and trim down the list of medications of their older patients before initiating chemotherapy. The electronization of medical records and prescribing offers opportunities for an integrated use of drug interaction software. Since not all PDIs can be

Disclosures and Conflict of Interest Statements

Dr. Popa is presently employed by Biovest International (this company has no relationships with the software used in this article). Dr. Extermann has research funding from Gtx and Dr. Balducci has honoraria from AMGEN, TEVA and Janssen. Drs. Wallace and Brunello have nothing to disclose. The work was supported in part by NIH funds.

Author Contributions

Study concept and design: M.A. Popa, M. Extermann, L. Balducci

Data acquisition: M.A. Popa, A. Brunello

Data analysis and interpretation: M.A. Popa, K. Wallace, M. Extermann, L. Balducci

Manuscript preparation: M.A. Popa, M. Extermann, L. Balducci

Manuscript editing and review: M.A. Popa, K. Wallace, A. Brunello, M. Extermann, L. Balducci

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