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Vandetanib: An overview of its clinical development in NSCLC and other tumors

A Morabito1, M C Piccirillo, R Costanzo

  • 1Medical Oncology, Thoraco-Pulmonary Department, National Cancer Institute, Napoli, Italy. alessandromorabito1@virgilio.it

Drugs of Today (Barcelona, Spain : 1998)
|October 23, 2010
PubMed

Insights

Vandetanib, an inhibitor of tumor growth pathways, showed efficacy in medullary thyroid cancer but limited benefit in non-small cell lung cancer. Further research is needed for optimal use and safety.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Vandetanib targets key kinases (VEGFR-2, EGFR, Ret) crucial for tumor growth, angiogenesis, and progression.
  • Phase I studies established a recommended dose of 300 mg/day, with common adverse events including rash, diarrhea, and hypertension.

Purpose of the Study:

  • To evaluate the efficacy and safety of vandetanib across various advanced cancers.
  • To assess vandetanib's role as a single agent and in combination therapies.

Main Methods:

  • Four randomized phase III trials investigated vandetanib in non-small cell lung cancer (NSCLC) with docetaxel, pemetrexed, or as a single agent.
  • Clinical trials also explored vandetanib in other cancers including small cell lung cancer, ovarian, colorectal, breast, prostate, multiple myeloma, and medullary thyroid cancer.

Main Results:

  • The ZODIAC trial met its primary endpoint for progression-free survival (PFS) in NSCLC when combined with docetaxel.
  • Vandetanib demonstrated significant improvements in response rate, PFS, and pain progression time in advanced metastatic medullary thyroid cancer.
  • No overall survival advantage was observed in NSCLC trials, and limited antitumor activity was noted in other investigated malignancies.

Conclusions:

  • Vandetanib shows promise in specific indications like medullary thyroid cancer but has a limited role in NSCLC, particularly regarding overall survival.
  • Key areas for future research include identifying predictive biomarkers, optimizing dosage and schedule, and assessing long-term safety.
  • Ongoing trials aim to clarify vandetanib's optimal clinical application in untreated advanced NSCLC and other tumor types.

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