Metronomic chemotherapy in hematology: lessons from preclinical and clinical studies to build a solid rationale for future schedules

Metronomic chemotherapy (mCHEMO), based on frequent, regular administration of low, but pharmacologically active drug doses, optimizes antitumor efficacy by targeting multiple targets and reducing toxicity of antineoplastic drugs. This minireview will summarize preclinical and clinical studies on cytotoxic drugs given at weekly, daily, or at continuous metronomic schedules alone or in combination with novel targeted agents for hematological malignancies, including lymphoma, multiple myeloma, and leukaemia. Most of the preclinical in vitro and in vivo studies have reported a significant benefit of both mCHEMO monotherapy and combinatorial regimens compared with chemotherapy at the maximum tolerated dose. However, the combination of mCHEMO with targeted drugs is still little explored in the hematologic clinical setting. Data obtained from preclinical studies on low dose metronomic chemotherapy in hematological malignancies clearly suggested the possibility to clinically investigate more tolerable and effective strategies for the treatment of patients with advanced hematological malignancies, or at least for those frail and elderly patients, who are not eligible or resistant to standard treatments.