• Metronomic chemotherapy
• colorectal cancer
• topotecan
• metastasis
• and animal models

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality and the fourth most common malignant neoplasm in the USA. Depending on the stage at diagnosis, liver and lung metastases occur in about 20–70% and 10–20% of patients, respectively. Unfortunately, distant metastases are the major cause of death for patients with advanced CRC. Despite use of standard therapies for metastatic CRC, treatment has only minimally improved survival, resulting in a medium survival of ∼2 years. As current chemotherapeutic drugs are used at maximum tolerated doses or high dose in standard therapies, toxicity remains a major issue for patients. Therefore, if the standard therapies could have prolonged breaks between successive cycles of drug administration, this could allow for recovery from toxic side effects. To solve this problem, Dr. Timothy Browder at Harvard Medical School first proposed metronomic chemotherapy to minimise toxicity by targeting the tumour-associated endothelium via frequent use of chemotherapeutic drugs at low doses over a longer period of time. Although the definition of metronomic chemotherapy varies, it now generally refers to the continuous administration of traditional chemotherapy, sometimes on a daily basis, at relatively low, minimally toxic doses, for longer periods. This emerging approach has been extensively evaluated in clinical trials and animal models.1 Hackl et al 2 report for the first time that metronomic oral topotecan therapy in adjuvant and metastatic settings prolongs survival and reduces liver metastasis in mouse models of metastatic CRC. Their findings provide a rational for clinical trials of metronomic oral topotecan …