Metronomic chemotherapy: An attractive alternative to maximum tolerated dose therapy that can activate anti-tumor immunity and minimize therapeutic resistance

Abstract

The administration of chemotherapy at reduced doses given at regular, frequent time intervals, termed ‘metronomic’ chemotherapy, presents an alternative to standard maximal tolerated dose (MTD) chemotherapy. The primary target of metronomic chemotherapy was originally identified as endothelial cells supporting the tumor vasculature, and not the tumor cells themselves, consistent with the emerging concept of cancer as a systemic disease involving both tumor cells and their microenvironment. While anti-angiogenesis is an important mechanism of action of metronomic chemotherapy, other mechanisms, including activation of anti-tumor immunity and a decrease in acquired therapeutic resistance, have also been identified. Here we present evidence supporting a mechanistic explanation for the improved activity of cancer chemotherapy when administered on a metronomic, rather than an MTD schedule and discuss the implications of these findings for further translation into the clinic.

Combinatorial Polymeric Conjugated Micelles with Dual Cytotoxic and Antiangiogenic Effects for the Treatment of Ovarian Cancer

“…The MTD chemotherapy in general is effective in cancers without a complex network of activating mutations such as gestational choriocarcinomas, testicular cancer, Hodgkin's disease, and Bcell non-Hodgkin's lymphoma 81 . Complex cancers such as ovarian, sarcoma, breast, prostate, and lung demonstrate poorer prognosis with conventional MTD treatment regimens 81 .…”

“…The MTD chemotherapy in general is effective in cancers without a complex network of activating mutations such as gestational choriocarcinomas, testicular cancer, Hodgkin's disease, and Bcell non-Hodgkin's lymphoma 81 . Complex cancers such as ovarian, sarcoma, breast, prostate, and lung demonstrate poorer prognosis with conventional MTD treatment regimens 81 . New advances in tumor biology suggest targeting the tumor microenvironment and not just the cancer cells through anti-angiogenic agents and reactivating host immune responses may provide better outcomes in complex cancers 20 .…”

Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial

“…The potential efficacy of metronomic chemotherapy depends on several mechanisms: inhibition of tumoral angiogenesis; reduction of the therapeutic resistance of the tumor; and activation of the adaptive and innate immune response [44,45].…”

Current applications and future prospects of nanomaterials in tumor therapy

“…2 Many methods have been developed for tumor therapy, such as immunotherapy, 3,4 gene therapy, 5,6 and radiofrequency ablation (RFA). [7][8][9] Nevertheless, traditional radiotherapy, 10,11 surgery, [12][13][14] and especially chemotherapy 15,16 are still the major strategies utilized in clinical tumor treatments. However, chemotherapy has a number of problems, including nonspecific distribution of the drug and the lack of tumor-specific treatments.…”