Elsevier

Annals of Oncology

Volume 15, Issue 10, October 2004, Pages 1543-1550
Annals of Oncology

Miscellaneous tumors
Metronomic therapy with cyclophosphamide induces rat lymphoma and sarcoma regression, and is devoid of toxicity

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ABSTRACT

Background

Our aim was to investigate the clinical efficacy and toxicity of metronomic administration of low-dose cyclophosphamide (Cy) in lymphoma and sarcoma rat tumour models.

Methods

Adult inbred rats were challenged with lymphoma TACB and sarcoma E100 s.c. on day 0. Animals were divided into two groups: group I, control, injected with saline three times a week; and group II, treated with Cy 10 mg/kg three times a week, from day 10 until the tumour was non-palpable, or 5 mg/kg three times a week from day 7. Tumours were measured and animals were weighed twice weekly. Periodic blood samples were taken for determination of urea, creatinine, serum glutamic-oxaloacetic transaminase, lactate dehydrogenase and haematological parameters.

Results

The administration of low-dose Cy eradicated established rat lymphomas and sarcomas; there was neither metastatic growth nor recurrence at primary sites for 100% of the lymphomas and 83% of the sarcomas. In addition, the treatment did not cause weight loss, and was devoid of haematological, cardiac, hepatic and renal toxicity.

Conclusions

Metronomic administration of Cy at low doses on a thrice weekly schedule to already grown rat lymphomas and sarcomas demonstrated itself to be a successful antitumour therapy that did not cause weight loss and was devoid of haematological, cardiac, hepatic and renal toxicity.

Keywords

cyclophosphamide
lymphoma
metronomic dosing
sarcoma
toxicity

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Present address: Hospital Universitario Vall d'Hebron, Laboratorio de Investigación Oncológica, Barcelona, Spain