Metastasis is the culmination of tumor progression and remains both the primary cause of mortality for cancer patients, as well as the most challenging aspect of cancer therapy. The main systemic treatment of metastatic disease – chemotherapy – was designed with the aim of killing as many tumor cells as possible by using cytotoxic agents at the maximum tolerated dose (MTD) [1, 2]. However, such regimens are associated with a number of inherent limitations. For instance, the administration of high dosages of chemotherapeutic agents results in toxicity, which is sometimes serious in nature (e.g., myelosuppression and damage to intestinal mucosa). As such, this requires the incorporation of prolonged breaks (often, three weeks) between treatments to allow recovery of depleted cells (e.g., neutrophils from bone marrow progenitors) [3]. Unfortunately, these breaks also allow for tumor regrowth to occur such that any regressions achieved by MTD therapy are usually only transitory [2]. In addition, due to the inherent ability of tumor cells to acquire resistance to cytotoxic agents, most MTD therapies eventually fail, resulting in resumption of disease progression. Overall, most MTD therapies have proven generally ineffective or of modest (mostly palliative) benefit in the treatment of advanced metastatic disease [3].

Clearly, a rethinking of approaches to treat metastatic disease is in order. This involves, at least in part, a reexamination of the dosing schedule regimens of chemotherapeutic agents that are best suited to treat this most intractable aspect of the pathology of cancer.