Urgent: Metronomic and conventional schedules of Cyclophosphamide in C57BL

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abd265's picture
Urgent: Metronomic and conventional schedules of Cyclophosphamide in C57BL

 I have recently started my project on cancer immunotherapy. I came across the paper Dr Browder has published few years ago. The paper is titled "Antiangiogenic Scheduling of Chemotherapy Improves Efficacy against Experimental Drug-resistant Cancer ", published in Cancer research journal in the year 2000. This paper demonstrated the efficacy of a new chemotherapy regimen for Cyclophosphamide and showed the anti-angiogenic effect of this schedule. It is a reference to many articles published later. I am using the same heterothopic model ( s.c injection of LLC cells in C57BL mice). As a metronomic gerimen, the author gave cyclophosphamide (170 mg/kg) s.c. every 6 days for two cycles, and then the tumor was allowed to grow.  However, from what I have learned metronomic chemotherapy  is  a method of giving the drug at a low dose, usually daily; but in that paper, cyclophosphamide was given at its  maximal tolerable dose (MTD) every 6 days. I could not contact neither Dr Browder, nor his supevisor Dr. Folkman since they have passed away few year ago. 
I have another question regarding conventional regimen, which is three times of 150 mg/kg every other day, followed by 2 weeks rest. I have performed a pre-experiment and used this regimen, but unfortunately 75% of the group's mice (10 mice/ group) started dying  from day 7 ( last dose was given on day 6). I am wondering anybody has faced any similar problem. if yes, have you performed any updates on the classic schedule in order to stop mice death?. In case, it's no, could you please tell me your personal suggestion ?

Best regards!