Randomized phase II trial of capecitabine versus capecitabine, low molecular weight heparin, and prednisone in refractory.......

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Author(s): E. Mak, C. Townsley, R. Buckman, E. Chen, L. Lopez, L. Wang, M. Moore, A. M. Oza; Princess Margaret Hospital, Toronto, ON, Canada
Capecitabine is widely used in the treatment of advanced colorectal
cancer. Continuous low dose chemotherapy has been postulated to have
anti-angiogenic effects discrete from its anti-proliferative effects on
tumors (metronomic therapy). Dalteparin and prednisone have also been
implicated in inhibiting tumour angiogenesis and hypothesized to have
additive benefit to chemotherapy. This randomized phase II study
examined the additive effect of dalteparin and prednisone with
capecitabine in metastatic colorectal cancer.
Methods: Patients with metastatic colorectal cancer were randomized to either capecitabine (C) 2,500 mg/m2
in divided doses from days 1-14 in a 3-week cycle or capecitabine with
dalteparin and prednisone (CDP). There was no restriction on previous
treatment, other than no prior capecitabine. Dalteparin was given at
5,000 units once daily subcutaneously, and prednisone orally 10 mg
daily, both on a continuous basis. Thirty patients were planned for
accrual in each arm with interim analysis when accrual reached fifteen
in each arm. The primary end-point was disease control defined as
treatment response or stable disease >4 months. Radiological
evaluation was performed every 6 weeks. Treatment was discontinued if
patients had progressive disease or intolerable toxicity.
Thirty patients were recruited. Fourteen patients had received ?3
previous regimens (median 3 (C), 2 (CDP)). Median performance statuses
were ECOG 1 (C) and 0 (CDP). Nine patients achieved stable disease
greater than 6 months (5 (C)/4 (CDP)). There was no statistical
difference in the median survival time and time-to- progression for the
two groups (11.1 mth (C)/15.8 mth (CDP); 3.2 mth (C)/2.8 mth (CDP)).
The commonest toxicities overall were myelosuppression and hand-foot
syndrome (HFS). The most common Grade 3+ adverse events were HFS (6
patients) and diarrhea (4 patients).
Conclusions: The
combination of dalteparin, prednisone and capecitabine did not improve
disease control over that seen with capecitabine in refractory
metastatic colorectal cancer.