C116
A trial of continuous low dose chemotherapy combined with celecoxib for patients with advanced cancer
Omar Khan1, Andrew Blann2, Miranda Payne1, Mark Middleton1, Andrew Protheroe1, Denis Talbot1, Oksana Kirichek1, Marian Taylor1, Cheng Han1, Adrian Harris1
1University of Oxford, UK, 2University of Birmingham, UK
Background
Low doses of chemotherapy given continuously (metronomic dosing) can be selectively toxic to proliferating endothelial cells in tumours, which tend to be resistant to standard episodic scheduling. Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial to treat advanced cancer patients.
Method
Patients received cyclophosphamide 50 mg od, celecoxib 400 mg bd for seven days each week and methotrexate 2.5 mg bd for two consecutive days each week orally. Response was determined every 8 weeks according to WHO criteria; toxicity was evaluated according to the CTC version 2.0 catalogue. Surrogate plasma markers of the endothelium, inflammation, coagulation and angiogenesis were measured.
Results
Sixty seven of 69 patients (median age, 60) were evaluable for response. Nineteen patients had stable disease after 8 weeks but there were no responses. Median time to progression was 65 days. The commonest adverse effect was fatigue and there was a low incidence of haematological and non-haematological toxicities. Amongst angiogenic markers, only matrix metalloproteinase levels were significantly higher amongst patients with progressive disease.
Conclusion
This metronomic approach has only minor efficacy in advanced cancer albeit with minimal toxicity. Patients with breast cancer had a longer median time to progression and more patients had stable disease than in the other tumour types. Further evaluation in metastatic breast cancer is warranted as metronomic approaches have led to some success in heavily pre-treated patients and consideration should be given to newer anti-angiogenic agents.
