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Phase II study of ZD1694 in patients with advanced gastric cancer
N J Meropol1, R Pazdur, M Vincent
1Division of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Abstract:
ZD1694 (Tomudex), a quinazoline folate analogue, is a potent and selective thymidylate synthase inhibitor. A phase II trial was undertaken to determine the efficacy and toxicity of ZD1694 in patients with advanced, measurable gastric adenocarcinoma. ZD1694, 3.0 mg/m2, was administered as a 15 min intravenous infusion every three weeks. Tumor measurements were obtained for response assessment every six weeks. Clinical examinations, adverse event assessments, and clinical laboratory tests were performed every three weeks. Thirty-three patients were enrolled. There were no objective responses to ZD1694. In general, treatment was well-tolerated. Grade 3 and 4 toxicities were infrequent, and included mucositis, nausea and vomiting, leukopenia, thrombocytopenia, and elevations of liver enzymes. Mild to moderate asthenia was common. Toxicities with ZD1694 were reversible and manageable. In conclusion, ZD1694 has an acceptable toxicity profile but shows no antitumor activity in patients with advanced gastric cancer.
Insights
ZD1694 (Tomudex), a thymidylate synthase inhibitor, showed no antitumor activity in advanced gastric cancer patients. The drug demonstrated an acceptable toxicity profile with manageable side effects.
Area of Science:
- Oncology
- Pharmacology
Background:
- Gastric adenocarcinoma is a significant cause of cancer-related mortality worldwide.
- Novel therapeutic agents are needed to improve outcomes for patients with advanced disease.
Purpose of the Study:
- To evaluate the efficacy and toxicity of ZD1694 (Tomudex), a thymidylate synthase inhibitor, in patients with advanced gastric adenocarcinoma.
Main Methods:
- A Phase II clinical trial was conducted.
- Thirty-three patients received ZD1694 at 3.0 mg/m2 intravenously every three weeks.
- Tumor response, clinical examinations, adverse events, and laboratory tests were assessed regularly.
Main Results:
- No objective responses were observed in any of the enrolled patients.
- Treatment was generally well-tolerated, with infrequent Grade 3 and 4 toxicities.
- Common toxicities included mucositis, nausea/vomiting, cytopenias, liver enzyme elevations, and asthenia, which were reversible and manageable.
Conclusions:
- ZD1694 exhibits an acceptable toxicity profile in patients with advanced gastric cancer.
- However, ZD1694 demonstrated no significant antitumor activity in this patient population.