The effect of low molecular weight heparin on survival in patients with advanced malignancy.
OBJECTIVE
Studies in cancer patients with venous thromboembolism suggested that low molecular weight heparin may prolong survival. In a double-blind study, we evaluated the effect of low molecular weight heparin on survival in patients with advanced malignancy without venous thromboembolism.


METHODS
Patients with metastasized or locally advanced solid tumors were randomly assigned to receive a 6-week course of subcutaneous nadroparin or placebo. The primary efficacy analysis was based on time from random assignment to death. The primary safety outcome was major bleeding.


RESULTS
In total, 148 patients were allocated to nadroparin and 154 patients were allocated to placebo. Mean follow-up was 1 year. In the intention-to-treat analysis the overall hazard ratio of mortality was 0.75 (95% CI, 0.59 to 0.96) with a median survival of 8.0 months in the nadroparin recipients versus 6.6 months in the placebo group. After adjustment for potential confounders, the treatment effect remained statistically significant. Major bleeding occurred in five (3%) of nadroparin-treated patients and in one (1%) of the placebo recipients (P = .12). In the a priori specified subgroup of patients with a life expectancy of 6 months or more at enrollment, the hazard ratio was 0.64 (95% CI, 0.45 to 0.90) with a median survival of 15.4 and 9.4 months, respectively. For patients with a shorter life expectancy, the hazard ratio was 0.88 (95% CI, 0.62 to 1.25).


CONCLUSIONS
A brief course of subcutaneous low molecular weight heparin favorably influences the survival in patients with advanced malignancy and deserves additional clinical evaluation.
Klerk
Clara P W
CP
Department of Vascular Medicine, Academic Medical Center F4-139, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.p.klerk@amc.uva.nl
Smorenburg
Susanne M
SM
Otten
Hans-Martin
HM
Lensing
Anthonie W A
AW
Prins
Martin H
MH
Piovella
Franco
F
Prandoni
Paolo
P
Bos
Monique M E M
MM
Richel
Dick J
DJ
van Tienhoven
Geertjan
G
Büller
Harry R
HR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D017762:Nadroparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy*; D010919:Placebos; D016019:Survival Analysis
D000925:Anticoagulants; D017762:Nadroparin; D010919:Placebos