Synopsis of randomized studies evaluating the treatment of cancer patients with low molecular weight heparins
| Study . | Study design . | No. of patients . | Study type . | Tumor entity . | Duration . | Result . |
|---|---|---|---|---|---|---|
| Lee et al (CLOT; 2005)100 | Dalteparin subcutaneously anti-Xa 200 IU/kg once daily for 1 month, then 150 IU/kg for 5 months versus dalteparin 200 IU/kg for1 week followed by a VKA | 676 | Multicenter, open-label, randomized, controlled | Solid tumors (colorectal, breast, lung, gynecologic, genitourinary, brain, pancreas) in patients with VTE | 6 months | No difference in survival at 12 months for the entire population; in the subgroup of patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group versus 36% in the VKA group (P = .03) |
| Altinbas et al (2004)101 | Chemotherapy alone versus dalteparin 5000 IU subcutaneously once daily and chemotherapy | 84 | Randomized, prospective | Small cell lung cancer | 18 weeks | Increase of median survival from 8 to 13 months (chemotherapy vs dalteparin plus chemotherapy, respectively; P = .01) |
| Kakkar et al (FAMOUS; 2004)102 | Placebo or dalteparin, 5000 IU subcutaneously per day | 385 | Randomized, double-blind, placebo-controlled | Advanced cancer breast, colorectal, ovarian, pancreatic, liver, genitourinary, uterus | 1 year | No significant benefit on overall survival at 1, 2, and 3 years after therapy; significant increase in survival after 2 years (78% vs 55%) and 3 years (60% vs 36%) in a subgroup with better prognosis (survival > 17 months; P = .03) |
| Klerk et al (MALT; 2005)103 | Nadroparin, adapted to body weight or placebo; administration twice daily for 14 days and once daily for another 4 weeks | 302 | Randomized, double-blind, placebo-controlled | Advanced cancer: lung, breast, colorectal, gastric or esophageal, melanoma, ovarian, pancreatic, liver, genitourinary, uterus, prostate, renal | 6 weeks | Increase of median survival from 6.6 to 8 months in the nadroparin group versus placebo, respectively (P = .021); in the patient group with an estimated life expectancy ≥ 6 months, median survival increased from 9.4 to 15.4 months (P = .01) |
| Sideras et al (2006)104 | Standard therapy with placebo or in combination with 5000 IU dalteparin subcutaneously per day | 138 | Phase 3, originally randomized, double-blinded, placebo-controlled, later changed to open-label | Advanced cancer: breast, colon, lung, or prostate | Life-long | No survival benefit for LMWH in patients with advanced cancer |
| Griffiths et al (FRAGMATIC; 2009)105 | Standard therapy alone or standard therapy plus dalteparin, 5000 IU subcutaneously per day | 2200 | Phase 3 clinical study, randomized, controlled, open-label | Small cell or nonsmall cell bronchial carcinoma | 24 weeks | Presently running study |
| Study . | Study design . | No. of patients . | Study type . | Tumor entity . | Duration . | Result . |
|---|---|---|---|---|---|---|
| Lee et al (CLOT; 2005)100 | Dalteparin subcutaneously anti-Xa 200 IU/kg once daily for 1 month, then 150 IU/kg for 5 months versus dalteparin 200 IU/kg for1 week followed by a VKA | 676 | Multicenter, open-label, randomized, controlled | Solid tumors (colorectal, breast, lung, gynecologic, genitourinary, brain, pancreas) in patients with VTE | 6 months | No difference in survival at 12 months for the entire population; in the subgroup of patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group versus 36% in the VKA group (P = .03) |
| Altinbas et al (2004)101 | Chemotherapy alone versus dalteparin 5000 IU subcutaneously once daily and chemotherapy | 84 | Randomized, prospective | Small cell lung cancer | 18 weeks | Increase of median survival from 8 to 13 months (chemotherapy vs dalteparin plus chemotherapy, respectively; P = .01) |
| Kakkar et al (FAMOUS; 2004)102 | Placebo or dalteparin, 5000 IU subcutaneously per day | 385 | Randomized, double-blind, placebo-controlled | Advanced cancer breast, colorectal, ovarian, pancreatic, liver, genitourinary, uterus | 1 year | No significant benefit on overall survival at 1, 2, and 3 years after therapy; significant increase in survival after 2 years (78% vs 55%) and 3 years (60% vs 36%) in a subgroup with better prognosis (survival > 17 months; P = .03) |
| Klerk et al (MALT; 2005)103 | Nadroparin, adapted to body weight or placebo; administration twice daily for 14 days and once daily for another 4 weeks | 302 | Randomized, double-blind, placebo-controlled | Advanced cancer: lung, breast, colorectal, gastric or esophageal, melanoma, ovarian, pancreatic, liver, genitourinary, uterus, prostate, renal | 6 weeks | Increase of median survival from 6.6 to 8 months in the nadroparin group versus placebo, respectively (P = .021); in the patient group with an estimated life expectancy ≥ 6 months, median survival increased from 9.4 to 15.4 months (P = .01) |
| Sideras et al (2006)104 | Standard therapy with placebo or in combination with 5000 IU dalteparin subcutaneously per day | 138 | Phase 3, originally randomized, double-blinded, placebo-controlled, later changed to open-label | Advanced cancer: breast, colon, lung, or prostate | Life-long | No survival benefit for LMWH in patients with advanced cancer |
| Griffiths et al (FRAGMATIC; 2009)105 | Standard therapy alone or standard therapy plus dalteparin, 5000 IU subcutaneously per day | 2200 | Phase 3 clinical study, randomized, controlled, open-label | Small cell or nonsmall cell bronchial carcinoma | 24 weeks | Presently running study |
VKA indicates vitamin K antagonist; VTE, venous thromboembolism; and LMWH, low molecular weight heparin.