Rationale for the use of metronomic chemotherapy in gastrointestinal cancer

Introduction: Metronomic chemotherapy (mCT) is endowed with various properties, ranging from antiangiogenic to immunomodulation, and may revert tumor resistance to conventional drug administration. A variety of antineoplastic agents displayed activity when administered with metronomic schedules in preclinical models of gastrointestinal cancers. However, most of the field is still unexplored. Areas covered: Herein, the authors review the existing literature from PubMed, concerning the use of mCT in gastrointestinal oncology. Expert opinion: A mounting body of evidence is emerging in support of mCT as a treatment option for gastrointestinal tumors, but the frequent signs of clinical activity inconsistently translate into a benefit for survival. Research in this field should focus on providing high-quality evidence on the safety and efficacy of mCT, with more prospective, comparative trials; identifying the subgroups of patients for whom mCT would be the best approach; establishing standardized protocols based on mCT pharmacokinetics and pharmacodynamics; developing drug activity biomarkers. mCT is also potentially suitable for combinations with targeted antiangiogenic drugs and may be incorporated with conventional administration into dual regimens.