Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS).
OBJECTIVE
In experimental systems, interference with coagulation can affect tumor biology. Furthermore, it has been suggested that low molecular weight heparin therapy may prolong survival in patients with cancer. The primary aim of this study was to assess survival at 1 year of patients with advanced cancer.


METHODS
Patients with advanced malignancy (N = 385) were randomly assigned to receive either a once-daily subcutaneous injection of dalteparin (5,000 IU), a low molecular weight heparin, or placebo for 1 year.


RESULTS
The Kaplan-Meier survival estimates at 1, 2, and 3 years after randomization for patients receiving dalteparin were 46%, 27%, and 21%, respectively, compared with 41%, 18%, and 12%, respectively, for patients receiving placebo (P =.19). In an analysis not specified a priori, survival was examined in a subgroup of patients (dalteparin, n = 55; and placebo, n = 47) who had a better prognosis and who were alive 17 months after randomization. In these patients, Kaplan-Meier survival estimates at 2 and 3 years from randomization were significantly improved for patients receiving dalteparin versus placebo (78% v 55% and 60% v 36%, respectively, P =.03). The rates of symptomatic venous thromboembolism were 2.4% and 3.3% for dalteparin and placebo, respectively, with bleeding rates of 4.7% and 2.7%, respectively.


CONCLUSIONS
Dalteparin administration did not significantly improve 1-year survival rates in patients with advanced malignancy. However, the observed improved survival in a subgroup of patients with a better prognosis suggests a potential modifying effect of dalteparin on tumor biology.
Kakkar
Ajay K
AK
Department of Surgical Oncology and Technology, and Cancer Research UK Laboratories, Imperial College, London, United Kingdom. akkakkar@tri-london.ac.uk
Levine
Mark N
MN
Kadziola
Zbigniew
Z
Lemoine
Nicholas R
NR
Low
Vanessa
V
Patel
Heman K
HK
Rustin
Gordon
G
Thomas
Michael
M
Quigley
Mary
M
Williamson
Robin C N
RC
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D017985:Dalteparin / Q000008:administration & dosage*; D004311:Double-Blind Method; D004739:England; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009864:Ontario; D016019:Survival Analysis; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000139:chemically induced / Q000517:prevention & control*
D000925:Anticoagulants; D017985:Dalteparin