Phase II study of docetaxel plus enoxaparin in chemotherapy-naive patients with metastatic non-small cell lung cancer: preliminary results.

Activation of coagulation appears to play a role in tumor progression. This report describes the preliminary results of a phase II study using docetaxel plus enoxaparin in 15 patients with stage IV non-small cell lung cancer (NSCLC). Time to progression was the primary endpoint. Several surrogate markers of coagulation and angiogenesis were evaluated. Enoxaparin was administered at a daily dose of 1 mg/kg (subcutaneously). The initial dose of docetaxel was 100 mg/m2, given as a 60 min infusion every 21 days with prophylactic dexamethasone. Eight patients achieved an objective response (53%) and four had stable disease, with a median duration of 3.5 months. The median time to progression was 5 months (range, 2 to >15 months). The median survival was 11 months. The most frequent toxicities were neutropenia and asthenia. No significant bleeding or thrombotic events were observed. Eleven patients had elevated D-dimer plasma levels prior to therapy, and seven of these patients with a response or stable disease had a significant decline of the D-dimer during therapy. There were no consistent changes of the plasma levels of the angiogenic factors, except for transforming growth factor-beta-1 (TGF-beta1). The median baseline level of TGF-beta1 prior to therapy was 34,867 pg/ml. Twelve out of 13 patients who achieved a response or stable disease had a significant reduction of the TGF-beta1 levels during therapy. Enoxaparin in combination with chemotherapy was safe and well tolerated in patients with advanced NSCLC. This preliminary data suggests that enoxaparin may prolong the time to progression, and therefore justify the continuation of this trial.