A new perspective in cancer treatment: Low dose metronomic chemotherapy with old known drugs in advanced breast cancer patients--Phase II clinical trial.

PERROUD HA; ALASINO CM; RICO MJ; MENACHO-MARQUEZ MA; MAINETTI LE; PEZZOTTO SM; QUERALT FN; ROZADOS VR; SCHAROVSKY OG

Chicago

Congreso; American Society of Clinical Oncology (ASCO) Annual Meeting; 2015

American Society of Clinical Oncology (ASCO)

Background: The oral administration of Cyclophosphamide (Cy) and Celecoxib (Cel)encourage the use of lowdose metronomic chemotherapy (MC) to treat heavily pretreated, multidrug resistant, advanced breast cancer patients (ABCP). Methods: Study design: Single arm, monoinstitutional, nonrandomized, phase II, two steps clinical trial (Approved by Bioethics Committee #5732/2007 and ANMATArgentine Regulatory Authority#4596/09). 15 patients were enrolled in the first stage, and 5 additional patients in the second one (β error = 0.100.20;α error = 0.05). Treatment plan: Cy 50 mg po.d+Cel 200 mg p.o bid. Patient eligibility criteria: 2180 years old, than 3 month of life expectancy,ABCP progressed to anthracyclines, taxanes and capecitabine, 4 chemotherapyschemes, at least 1 measurable lesion (RESIST 1.1), ECOG scale 2, appropriate bone marrow and renal function. Informed consent signed. Primary endpoint: Progression free survival (PFS) and clinical benefit (CB). Results: The main clinical outcomes were prolonged disease stabilization (SD > 24 weeks) in 10/20 patients (50%) and partial remission (PR) in 1/20 (5%). No complete remissions (CR) were observed. Response rate was 5% (CR+PR: 1/20). CB was 55% (PR+SD 24 weeks: 11/20). TTP was 21.1 weeks (median: 15.5, range: 381). Median TTP in patients who achieved CB was 35.6 weeks (median: 27, range: 2481). PFS at 24 weeks was 50%. Overall survival (OS) rate 1 year after enrollment was 25%. Mean OS was 44.20 weeks (median: 36 range: 5.14232.14 weeks). There were no grade 3/4 toxicities associated to treatment. Quality of life did not change or improved transiently in a high proportion of patients. Conclusions: Treatment was effective to control advanced disease in this group of patients, with a low toxicity profile and excellent tolerability. These results encourage the use of this MC scheme in heavily pretreated ABCP, as well as the development of new oral MC schemes that do not affect the quality of life. Although the main objective was not the evaluation of effectiveness in elderly patients, due to the lack of toxicity and clinical benefit, this kind of treatment could be a valid option for this group of patients