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Drug resistance and the role of combination chemotherapy in improving patient outcomes.

ABSTRACT: Resistance to cancer chemotherapy is a common phenomenon especially in metastatic breast cancer (MBC), a setting in which patients typically have had exposure to multiple lines of prior therapy. The subsequent development of drug resistance can result in rapid disease progression during or shortly after completion of treatment. Moreover, cross-class multidrug resistance limits patient treatment choices, particularly in a setting where treatments options are few. One attempt to minimize the impact of drug resistance has been the concurrent use of two or more chemotherapy agents with unrelated mechanisms of action and differing modes of drug resistance, with the intent of blocking the development of multiple intracellular escape pathways essential for tumor survival. Within the past decade, an array of mechanistically diverse agents has augmented the list of combination regimens that may be both synergistic and efficacious in pretreated MBC. The aim of this paper is to review mechanisms of resistance to common chemotherapy agents and to consider current combination treatment options for heavily pretreated and/or drug-resistant patients with MBC.

SUBMITTER: Yardley DA

PROVIDER: S-EPMC3707274 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Drug resistance and the role of combination chemotherapy in improving patient outcomes.

Yardley Denise A DA

International journal of breast cancer 20130624

Resistance to cancer chemotherapy is a common phenomenon especially in metastatic breast cancer (MBC), a setting in which patients typically have had exposure to multiple lines of prior therapy. The subsequent development of drug resistance can result in rapid disease progression during or shortly after completion of treatment. Moreover, cross-class multidrug resistance limits patient treatment choices, particularly in a setting where treatments options are few. One attempt to minimize the impac ...[more]

PMID: 23864953

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Project description:BackgroundHigh-value cancer care balances effective treatment with preservation of quality of life. Chemotherapy is known to affect patients' physical and psychological well-being negatively. Patient-reported outcomes (PROs) provide a means to monitor declines in a patients' well-being during treatment.MethodsWe identified 741 oncology patients undergoing chemotherapy in our electronic health record (EHR) system who completed Patient-Reported Outcomes Measurement Information System (PROMIS) surveys during treatment at a comprehensive cancer center, 2013-2018. PROMIS surveys were collected before, during, and after chemotherapy treatment. Linear mixed-effects models were performed to identify predictors of physical and mental health scores over time. A k-mean cluster analysis was used to group patient PROMIS score trajectories.ResultsMean global physical health (GPH) scores were 48.7 (SD 9.3), 47.7 (8.8), and 48.6 (8.9) and global mental health (GMH) scores were 50.4 (8.6), 49.5 (8.8), and 50.6 (9.1) before, during, and after chemotherapy, respectively. Asian race, Hispanic ethnicity, public insurance, anxiety/depression, stage III cancer, and palliative care were predictors of GPH and GMH decline. The treatment time period was also a predictor of both GPH and GMH decline relative to pre-treatment. Trajectory clustering identified four distinct PRO clusters associated with chemotherapy treatment.ConclusionsPatient-reported outcomes are increasingly used to help monitor cancer treatment and are now a part of care reimbursement. This study leveraged routinely collected PROMIS surveys linked to EHRs to identify novel patient trajectories of physical and mental well-being in oncology patients undergoing chemotherapy and potential predictors. Supportive care interventions in high-risk populations identified by our study may optimize resource deployment.Novelty and impactThis study leveraged routinely collected patient-reported outcome (PROMIS) surveys linked to electronic health records to characterize oncology patients' quality of life during chemotherapy. Important clinical and demographic predictors of declines in quality of life were identified and four novel trajectories to guide personalized interventions and support. This work highlights the utility of monitoring patient-reported outcomes not only before and after, but during chemotherapy to help advert adverse patient outcomes and improve treatment adherence.

Project description:National Institute for Health and Care Excellence (NICE) guidelines state that all healthcare organisations should put policies in place for medication reconciliation on admission. At Croydon University Hospital a medication history had previously been taken in Foundation Year 1 (FY1) preoperative clinics. However, when these clinics were deemed unnecessary, this opportunity for drug chart documentation was lost, along with an awareness of this responsibility among the FY1s. As a result patients were being admitted to wards without adequate drug chart documentation which resulted in a serious untoward incident occurring. This project aimed to increase awareness among FY1s of this responsibility and as a result increase drug chart documentation in postoperative elective surgical patients. The drug charts of 40 postoperative elective surgical patients admitted to all surgical wards were reviewed over a 2 week period. 12.5% (4/32) of patients taking regular medication had these correctly prescribed, with 'high risk medication omissions' found in 7.5% (3/40). Documentation of an allergy status was absent in 17.5% (7/40) of patients, including 5% (2/40) of whom had a known drug allergy. To create awareness of this responsibility, first, a presentation was given to the FY1s, second, posters to prompt action were placed on the elective surgical wards, and finally, the Director of Medical Education emailed the FY1s reiterating these facts. We then reviewed the drug charts of 45 elective postoperative patients over a 2 week period following these interventions. The results showed: correct prescription of regular medications improved to 48% (16/33); 'high risk medication omissions' reduced to 4% (2/45); documentation of allergy status on the drug charts increased to 87% (39/45); failure to document a known drug allergy on the drug chart fell to 2% (1/45); and patients with a 'high risk medication omission' or an undocumented known drug allergy decreased from 12.5% (5/40) to 7 % (3/45). This study has highlighted an area in which medication reconciliation and drug chart documentation were inadequate, and posed a risk to patient safety. Interventions designed to educate the FY1s and inform them of their responsibility improved standards in regular medication prescription and allergy documentation. However, leaving the onus with the FY1s was not enough to achieve adequate drug chart documentation. Further project cycles may therefore require the implementation of a step within the patient admission protocol in the preoperative ward that requires the nursing staff to contact the team's doctor when the patient arrives in hospital to ensure satisfactory drug chart documentation. In addition, collaboration with the pharmacists could also allow a 'best possible medication history' to be taken on the day of admission and thus reduce risk to patient safety.

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Drug resistance and the role of combination chemotherapy in improving patient outcomes.

Publications

Drug resistance and the role of combination chemotherapy in improving patient outcomes.

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