Rationale for the use of metronomic chemotherapy in gastrointestinal cancer

ABSTRACT

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.

KEYWORDS:

• Metronomic chemotherapy
• gastrointestinal tumors
• capecitabine
• cyclophosphamide
• pancreatic cancer
• colorectal cancer
• hepatocellular carcinoma
• gastric cancer; biliary cancer

Article highlights

• Metronomic chemotherapy is an approach intended for low toxicity, and differs from conventional chemotherapy in a spectrum of biological activities, which ultimately results in gross volumetric tumor stabilization.

• The body of preclinical and clinical literature concerning metronomic chemotherapy in gastrointestinal oncology has grown to a considerable extent, yet many questions are still unanswered.

• Although showing encouraging signs of activity in gastrointestinal cancers, the quality of evidence is heterogeneous, and only two published phase-III studies exist to date, which evaluated metronomic capecitabine as a maintenance treatment in metastatic colorectal cancer.

• Improving research may benefit from a closer definition of populations potentially gaining the maximum benefit from metronomic administration.

• Multiple evolutionary paths of metronomic chemotherapy are foreseeable, such as the combination with antiangiogenic drugs, the incorporation into complex schemes, and the use as a platform for cancer vaccines or nanocarriers.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.