Phase I-II study of DalCM-P [daily dalteparin (Dal), cyclophosphamide (C) and prednisone (P) and bi-weekly methotrexate (M)] as therapy for metastatic breast cancer (MBC)

695 Background: Preclinical and clinical studies indicate that metronomic chemotherapy (dosing at close, regular intervals with no prolonged breaks) inhibits tumour growth through antiangiogenesis. Metronomic C and M have activity in MBC while Dal (‘Fragmin’) and P have anti-angiogenic activity and are synergistic. We designed a two-stage phase I-II study of DalCM-P in MBC (α=5%, β=10%, Po=5% and P1=20%). Methods: Patients with measurable MBC, adequate end-organ function and performance status, and life expectancy >6 months, who had received ≥2 types of chemotherapy for MBC, or were deemed unsuitable for standard 1st or 2nd line chemotherapy were eligible. Treatment was C 50mg and P 5mg by mouth (po) daily, M 2.5mg po twice daily Mon and Tue, and Dal 5000 IU subcutaneously daily, all given continuously. End points were specified as response rate (RR), time to progression (TTP) and overall survival (OS) using standard RECIST criteria. Results: At interim analysis (Sept 2004), 32 patients were accrued. Characteristics were: median age 56 (range 30–84); hormone receptors positive 22 (68.8%); Her-2 negative 18 (56.3%); visceral disease 24 (75.0%); ≥3 sites of metastases 8 (25.0%); disease free survival >1 year 29 (90.6%). Sixteen (50%) had no prior chemotherapy for MBC; 6 (18.8%) had 1 prior regimen; 10 (31.3%) had ≥2 prior regimens. The only ≥ grade 3 toxicities were transient grade 3 transaminitis in 8 patients (25.0%) and grade 3 vomiting in 1 (3.1%). One patient (3.1%) had complete response (CR), 4 (12.5%) had partial response (PR), 2 (6.3%) had prolonged stable disease ≥ 6 mos (PSD) for an overall response rate (CR+PR+PSD) of 7 (21.9%). Of the 16 with no prior chemotherapy for MBC, 1 had CR, 3 PR and 0 PSD (CR+PR+PSD = 4 (25%)). The median TTP was 1.8 mos (range 0.1–9.1+ mos) and median OS 18.3 mos (range 1.1–18.3+ mos). Data will be available on all 41 patients in May, 2005. Conclusions: DalCM-P is safe, well tolerated and demonstrates clinical activity in MBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Biomira, Ortho-Biotech, Pfizer, Pharmacia, Roche, YM Biosciences AstraZeneca, Aventis, Eli Lilly, Novartis, Pfizer, Pharmacia, Roche, Schering AstraZeneca, Aventis

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