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Updated: Jun 27, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
An open-label study of vandetanib with pemetrexed in patients with previously treated non-small-cell lung cancer
1Department of Medical Oncology, Western Hospital, Melbourne, Australia. richard.deboer@wh.org.au
Background:
Vandetanib (ZACTIMA; 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.
Insights
Vandetanib combined with pemetrexed showed good safety in advanced non-small-cell lung cancer (NSCLC) patients. The combination therapy was well-tolerated, with manageable side effects in this clinical trial.
Area of Science:
- Oncology
- Pharmacology
Background:
- Vandetanib is an oral inhibitor targeting vascular endothelial growth factor receptor and epidermal growth factor receptor signaling pathways.
- This study evaluated the safety and tolerability of combining vandetanib with pemetrexed in advanced non-small-cell lung cancer (NSCLC).
Purpose of the Study:
- To assess the safety and tolerability of vandetanib plus pemetrexed in patients with advanced non-small-cell lung cancer (NSCLC).
- To determine dose-limiting toxicities (DLTs) for the combination therapy.
Main Methods:
- Patients with previously treated advanced NSCLC (stage IIIB/IV) received daily oral vandetanib (100 or 300 mg) concurrently with pemetrexed (500 mg/m(2) intravenously every 21 days).
- Safety was evaluated based on the incidence of dose-limiting toxicities (DLTs) and adverse events.
Main Results:
- The combination met the protocol definition for tolerable dosing, with one DLT in each cohort (QTc prolongation in the 100 mg group, interstitial lung disease in the 300 mg group).
- Most common adverse events included rash, anorexia, fatigue, and diarrhea, reported in all patients.
- The interstitial lung disease in the 300 mg cohort resolved with steroid treatment.
Conclusions:
- Vandetanib and pemetrexed combination therapy is generally well-tolerated in patients with advanced NSCLC.
- The observed adverse events were manageable, suggesting potential for this combination in NSCLC treatment.
