Low-molecular-weight heparin adherence and effects on survival within a randomised phase III lung cancer trial (RASTEN)

Abstract

Background: Coagulation activation is a hallmark of cancer, and anticoagulants have shown tumour-inhibiting properties. However, recent trials have failed to demonstrate improved survival with low-molecular-weight heparin (LMWH) in cancer populations. This has raised the question of suboptimal adherence as a possible explanation for the lack of benefit. Still, there is no standardised method to directly monitor LMWH in patient plasma. Here, we directly determine LMWH levels in patients using the Heparin Red assay to objectively assess adherence and how this associates with the patient outcome in the RASTEN trial. Methods: RASTEN is a multicentre, randomised phase III trial investigating if the addition of LMWH to standard therapy can improve survival in small-cell lung cancer. LMWH was measured in plasma (N Z 258) by the Heparin Red assay and compared with the antiefactor Xa (anti-FXa) activity assay. Results: Both methods could differentiate patients in the LMWH arm from the control arm and patients receiving therapeutic LMWH owing to thrombosis. Receiver Operating Characteristic (ROC) analysis yielded adherence rates of 85% for anti-FXa and 68% for

Safety profile of preoperative administration of low-molecular-weight heparin on minimally invasive lung cancer surgery: a randomized controlled trial

“…Altinbas et al considered small cell lung cancer patients receiving chemotherapy plus LMWH could gain benefits of progression free survival (PFS) and overall survival [27,29]. However, Gezelius et al conducted a clinical phase III lung cancer trial revealed that addition of LMWH could not provide any survival benefit for small cell lung cancer patients [30,31]. Other investigators made the same conclusion that LMWH did not demonstrate detectable survival advantage for non-small cell lung cancer patients [32,33].…”

Néoplasie révélée par un épisode thromboembolique veineux. Données du registre REMOTEV

“…Cependant, les dernières études réalisées, et notamment l'étude RASTEN [78] n'a pas réussi à démontrer d'impact sur la survie de patients atteints de cancers pulmonaire et bénéficiant d'une cure d'HBPM. L'hypothèse initiale de cette étude était que certains patients ne sont pas répondeurs au traitement par HBPM.…”

Do we need prophylactic anticoagulation in ambulatory patients with lung cancer? A review

“…Interestingly, adherence to the treatment did not correlate with better survival, excluding the nonadherence as a potential cause of bias. 48 An increase in overall survival was not proven in the FRAGMATIC trial, which is the largest one involving patients with lung cancer. Regarding the incidence of VTE events, a statistically significant reduction was reported in the PROTECHT, FRAGMATIC, SAVE-ONCO, and RASTEN trials, as well as in the TOPIC-2 study in the subgroup of patients with lung cancer stage IV.…”