The anti-angiogenic basis of metronomic chemotherapy

A pharmacokinetic and pharmacodynamic study on metronomic irinotecan in metastatic colorectal cancer patients

“…Moreover, this suggests further clinical steps that might be explored such as the administration of rubitecan, an oral camptothecin (Clark, 2006), or combination studies with other low-dose oral chemotherapeutic drugs already approved for colorectal cancer such as UFT (Munoz et al, 2006) or capecitabine. In addition, combination of a targeted antiangiogenic drug such as bevacizumab with metronomic irinotecan therapy might also be considered in patients not previously treated with this drug since such combinations show much greater antitumour efficacy compared to metronomic chemotherapy alone or the antiangiogenic drug alone (Klement et al, 2000;Kerbel and Kamen, 2004;Pietras and Hanahan, 2005).…”

“…Colleoni and co-workers have used the metronomic/antiangiogenic strategy, mainly based on the use of daily oral cyclophosphamide (CTX) in combination with low-dose methotrexate given 2 days/week, in clinical trials for the treatment of metastatic breast cancer patients, and reported promising clinical activity in the absence of serious adverse events (Colleoni et al, 2002(Colleoni et al, , 2006Orlando et al, 2006a, b). Moreover, the lowtoxicity profile (Kerbel and Kamen, 2004) and the low costs (Bocci et al, 2005b) of the metronomic CTX regimens enhanced the quality of life of patients and suggested immediate potential use in various clinical settings. Glode et al (2003) and Vogt and co-workers (Vogt et al, 2003;Coras et al, 2004) studied a metronomic chemotherapy schedule based on alkylating agents (CTX and trofosfamide, respectively) in combination with drugs thought to have some antiangiogenic effects (i.e., dexamethasone, rofecoxib and pioglitazone), demonstrating efficacy as a salvage therapy in the treatment of patients with hormone-refractory prostate carcinoma (Glode et al, 2003) or palliative treatment of patients with advanced malignant vascular tumours (Vogt et al, 2003) and endemic Kaposi sarcoma (Coras et al, 2004).…”

Cisplatin, Etoposide, and Bevacizumab Regimen Followed by Oral Etoposide and Bevacizumab Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer: A Single-Institution Experience

“…Oral E administered for a long period of time might be defined as metronomic chemotherapy and it might overcome drug resistance by targeting tumor vasculature. 29 Indeed, it has been suggested that the repeated exposure to low-dose metronomic treatment with oral E might impair the angiogenic potential of endothelial cells and increase their chemosensitivity. 30 These preclinical data might further support the rationale for the current study in which, indeed, the combination of the antiangiogenic agent Bev with low-dose metronomic oral E was used as maintenance treatment after induction chemotherapy in patients with ED-SCLC who responded to treatment.…”

Role of endothelial progenitor cells in breast cancer angiogenesis: from fundamental research to clinical ramifications

“…Accordingly, addition of an antibody against CXCR4 to block EPC mobilization enhanced the antitumor effect of docetaxel in a murine breast cancer model [62]. In line with this, the efficacy of metronomic chemotherapy was thought to be mainly antiangiogenic [63,64]. Metronomic chemotherapy is defined as regular administration of a chemotherapeutic drug at relatively low (nontoxic) doses, over prolonged periods, with no extended drug-free break periods [63].…”

“…In line with this, the efficacy of metronomic chemotherapy was thought to be mainly antiangiogenic [63,64]. Metronomic chemotherapy is defined as regular administration of a chemotherapeutic drug at relatively low (nontoxic) doses, over prolonged periods, with no extended drug-free break periods [63]. Using different preclinical breast cancer models, several studies showed a strong relationship between decreased number of circulating EPC and efficiency of various metronomic chemotherapy regimens [65][66][67][68].…”