To the Editor First of all, we congratulate Pramanik et al1 for carrying out the first randomized clinical trial in the field of metronomic chemotherapy. However, we would like to raise some pertinent issues.
This protocol does not exactly fit the definition of metronomic chemotherapy, that is, “long-term administration of chemotherapeutic agents in a relatively low, minimum toxic dose with no prolonged drug-free breaks.” The doses of cyclophosphamide at 2 mg/kg (up to 100 mg per day), as well as 400 mg per day dose of celecoxib, are not exactly in the “relatively low” dose range. Similarly, cyclophosphamide was given from day 22 to 42 in the first 63 days. So in the first 3 cycles, patients will have a cyclophosphamide-free period of 67%! Also, the etoposide-free period is 50% in the first 42 days. These are actually long breaks. Both points are against the principles of metronomics. Unlike in maximum tolerated dose–based protocols, presently the selection of patients, drug dosages, and dosing intervals in metronomic therapies is empirical and thus needs more research.