- Lancet Oncol. 2009 Aug 31.
for the prevention of thromboembolic events in ambulatory patients with
metastatic or locally advanced solid cancer receiving chemotherapy: a
randomised, placebo-controlled, double-blind study.
Agnelli G, Gussoni G, Bianchini C, Verso M, Mandalà M, Cavanna L, Barni S, Labianca R, Buzzi F, Scambia G, Passalacqua R, Ricci S, Gasparini G, Lorusso V, Bonizzoni E, Tonato M; on behalf of the PROTECHT Investigators.
Internal and Vascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy.
Clinical trials are needed to assess the clinical benefit of
antithrombotic prophylaxis in patients with cancer who are receiving
chemotherapy, since these patients are at an increased risk of
developing a thromboembolism. We did a trial to assess the clinical
benefit of the low-molecular-weight heparin nadroparin for the
prophylaxis of thromboembolic events in ambulatory patients receiving
chemotherapy for metastatic or locally advanced solid cancer.
Between October, 2003, and May, 2007, ambulatory patients with lung,
gastrointestinal, pancreatic, breast, ovarian, or head and neck cancer
were randomly assigned in a double-blind manner to receive subcutaneous
injections of nadroparin (3800 IU anti-Xa once a day, n=779) or placebo
(n=387), in a 2:1 ratio. Study treatment was given for the duration of
chemotherapy up to a maximum of 4 months. The primary study outcome was
the composite of symptomatic venous or arterial thromboembolic events,
as assessed by an independent adjudication committee. All randomised
patients who received at least one dose of study treatment were
included in the efficacy and safety analyses (modified
intention-to-treat population). The study is registered with
ClinicalTrials.gov, NCT 00951574.
FINDINGS: 1150 patients were included
in the primary efficacy and safety analyses: 769 patients in the
nadroparin group and 381 patients in the placebo group. 15 (2.0%) of
769 patients treated with nadroparin and 15 (3.9%) of 381 patients
treated with placebo had a thromboembolic event (single-sided p=0.02).
Five (0.7%) of 769 patients in the nadroparin group and no patients in
the placebo group had a major bleeding event (two-sided p=0.18). The
incidences of minor bleeding were 7.4% (57 of 769) with nadroparin and
7.9% (30 of 381) with placebo. There were 121 (15.7%) serious adverse
events in the nadroparin goup and 67 (17.6%) serious adverse events in
the placebo group.
INTERPRETATION: Nadroparin reduces the incidence of
thromboembolic events in ambulatory patients with metastatic or locally
advanced cancer who are receiving chemotherapy. Future studies should
focus on patients who are at a high risk for thromboembolic events.
FUNDING: Italfarmaco SpA, Milan, Italy.