Clinical Outcomes Associated with Drug–Drug Interactions of Oral Chemotherapeutic Agents: A Comprehensive Evidence-Based Literature Review

  • Manvi SharmaEmail author
  • Aisha Vadhariya
  • Soumya Chikermane
  • Suma Gopinathan
  • Mariana Chavez-MacGregor
  • Sharon H. Giordano
  • Michael L. Johnson
  • Holly M. Holmes
Review Article



Oral chemotherapy use is increasing due to new drug approvals as well as the convenience of the administration of oral drugs. This increased use also raises concern regarding drug–drug interactions (DDIs) with concomitantly administered drugs, resulting in loss of therapeutic effect, decreased tolerability, and/or increased toxicity.


The objective of this study was to review existing evidence of the clinical impact of DDIs with oral chemotherapeutic agents.


A comprehensive search of literature using PubMed was conducted in April 2018 for studies of DDIs associated with oral chemotherapy. Included studies were in English. We included randomized clinical trials, observational studies, and case reports evaluating a DDI between any oral chemotherapy drug and any other drug. Included studies needed to have at least one outcome of clinical relevance potentially attributed to the DDI, for example, effects on survival or toxicity. The quality of the articles was determined using published metrics appropriate for the study design.


There were 2626 studies identified in the initial search, of which 35 met all eligibility criteria. These included 15 retrospective cohort studies, 16 case reports or case series and four post hoc analyses of clinical trials. Among these, DDIs contributed to a statistically significant change in a clinical outcome in 12 studies. Eight of these studies evaluated overall survival and progression-free survival and found that the presence of the DDI was associated with reduced survival.


Our findings suggest that more real-world studies evaluating the association between oral chemotherapy DDIs and clinical outcomes are needed. The adverse clinical outcomes due to DDIs may be a reason for treatment failures and therapy discontinuation.


Compliance with Ethical Standards


The work in this manuscript was supported in part by CCSG P30 CA016672, a Cancer Center Support (CORE) grant to MD Anderson Cancer Center.

Conflict of interest

Mariana Chavez-MacGregor has received institutional research support from Novartis. Manvi Sharma, Aisha Vadhariya, Soumya Chikermane, Suma Gopinathan, Sharon H. Giordano, Michael L. Johnson, and Holly M. Holmes declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmacy AdministrationThe University of MississippiOxfordUSA
  2. 2.Department of Pharmaceutical Health Outcomes and PolicyUniversity of HoustonHoustonUSA
  3. 3.Department of Breast Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Health Services ResearchThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Division of Geriatric and Palliative Medicine, McGovern Medical SchoolThe University of Texas Health Science CenterHoustonUSA

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