An open-label study of vandetanib with pemetrexed in patients with previously treated non-small-cell lung cancer

Background: Vandetanib (ZACTIMA (TM); ZD6474) is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The safety and tolerability of vandetanib plus pemetrexed was assessed in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients with previously treated NSCLC (stage IIIB/IV) received once-daily oral vandetanib (100 or 300 mg) with pemetrexed (500 mg/m(2) i.v. infusion every 21 days). Results: Patients received vandetanib 100 mg + pemetrexed (n = 10) or vandetanib 300 mg + pemetrexed (n = 11). The protocol definition of a tolerable dose [vandetanib-related dose-limiting toxicity (DLT) in less than 2 patients] was met in both dose cohorts, with one DLT reported in each: asymptomatic QTc prolongation (> 100 ms increase from baseline, but absolute QTc < 500 ms) in the 100 mg cohort and interstitial lung disease, which resolved after steroid therapy, in the 300 mg cohort. The most common adverse events were rash, anorexia, fatigue and diarrhea (all n = 10). Conclusion: Vandetanib and pemetrexed in combination were generally well tolerated in patients with advanced NSCLC.