1. Pasquier E, Kavallaris M, André N. Metronomic chemotherapy: new rationale for new directions. Nature Rev Clin Oncol 2010;7:455-465.
2. André N, Padovani L, Verschuur A. Metronomic chemotherapy: back to the future. Drug News Perspectives 2010;23: 143-151.
3. Kerbel RS, Kamen BA. The antiangiogenic basis of metronomic chemotherapy. Nature Rec Cancer 2004;4:423-436.

In the US, the active agent of MNX-200 is approved as a component of first-line therapy for patients with metastatic cancer. MetronomX is developing a proprietary oral metronomic formulation of this chemotherapeutic agent coded as MNX-200. The commercially available formulation of MNX-200 is for IV administration but several Phase 1 trials have established safe and antitumor-active doses and schedules of MNX-200 given orally using various oral formulations. Also oral administration of MNX-200 appears to have fewer of the side effects associated with IV administration. Clearly oral administration of MNX-200 would also afford patient convenience and lower cost of drug administration, especially for metronomic regimens (long-term daily dosing).

Laboratory and early clinical studies have shown that metronomic (i.e., low-dose, frequent, long-term or continuous) administration of anticancer drugs has the potential to improve both efficacy and safety compared to conventional treatment based on maximum tolerated doses (MTD) with long treatment holidays required to allow recovery of normal tissues (1,2).

The metronomic mode of treatment is hypothesized to disrupt tumor angiogenesis more effectively and selectively than conventional, MTD-based regimens (reviewed in Reference 3). In addition recent laboratory studies suggest that metronomic regimens may activate immune-mediated anticancer mechanisms and induce tumor dormancy (3).

Encouraging results have emerged from clinical studies of metronomic regimens of the orally administered cytotoxics cyclophosphamide, etoposide, temozolomide and capecitabine, as well as the anti-angiogenic monoclonal antibody bevacizumab and the COX-2 inhibitor celecoxib (1,2). MNX-200 is an exciting candidate for clinical studies of metronomic administration, either as a single agent or in combination with other cytotoxics and/or angiogenesis-targeted agents.

MNX-200 Clinical Development

This study is planned to be a multicenter, open-label study in 24 advanced or metastatic pediatric cancer patients. The phase I trial will not be disease specific, but open to all patients having disease refractory to standard therapy but otherwise healthy enough to take oral medication and have an estimated 4-6 week survival, as for typical phase I trials. The primary objectives of the study will be to evaluate the safety and tolerability of oral administered MNX-200 at pharmacologically active metronomic doses during daily repeated, ascending dose administration to metastatic or locally advanced pediatric cancer patients.