Single Agent Metronomic Cyclophosphamide in Refractory,Non-Hodgkin's Lymphoma.

Abstract 4776

n this retrospective review, we report a case series of eight patients with refractory, heavily pre-treated non-Hodgkin's lymphoma(NHL), treated with low dose cyclophosphamide. Median number of prior treatment regimens was 3. The median disease free survival was 15.5 months with three patients in ongoing CR at the time of reporting with 15 - 36 months of followup. In a comparative group of 6 patients with other malignancies beside NHL (3 chronic lymphocytic leukemia, 2 breast cancer, 1 thymoma, and one small cell carcinoma) the median progression free survival was significantly worse at 3 months. Interestingly the thymoma had a progression free survival of 36 months.

Toxicity was minimal. One patient stopped because of thrombocytopenia. One of the patients with ongoing CR at 36 months stopped after 11 months of treatment. One patient died in CR of anal cancer after 15 months of treatment.

These results demonstrate an easily tolerable and surprisingly effective treatment option in patients with non-Hodgkin's lymphoma who are not candidates for bone marrow transplantation.

The mechanism of action of metronomic chemotherapy has been proposed as anti-angiogenic. We suggest an alternate mechanism of action: that of immunomodulation. We are suggesting this alternate explanation in view of the significant difference in the response rate between those disease that are known to immunogenic and those that may be less so, as well as the well-known immunogenic affect of cyclophosphamide. Further studies are ongoing to investigate this hypothesis.