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ZD-9331 AstraZeneca.

I Niculescu-Duvaz¹

¹CRC Centre for Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey, SM2 5NG.

Current Opinion in Investigational Drugs (London, England : 2000)

|March 16, 2001

Summary

This summary is machine-generated.

ZD-9331, a novel thymidylate synthase inhibitor, shows promise for treating solid tumors. Early trials indicate myelosuppression is the dose-limiting toxicity, comparable to existing treatments.

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Area of Science:

Oncology
Pharmacology

Background:

AstraZeneca is developing ZD-9331, a non-polyglutamatable thymidylate synthase inhibitor.
It is being investigated as a treatment for solid tumors, including colorectal cancer.

Purpose of the Study:

To evaluate the safety and efficacy of ZD-9331 in patients with solid tumors.
To determine the dose-limiting toxicity and maximum tolerated dose (MTD) of ZD-9331.

Main Methods:

Phase I and II clinical trials were conducted.
Dose escalation studies were performed to identify the MTD.
Intracellular 2'-deoxyuridine (dUrd) elevation was measured as a marker of thymidylate synthase inhibition.

Main Results:

Myelosuppression was identified as the dose-limiting toxicity in Phase I studies.

Related Experiment Videos

ZD-9331 demonstrated intracellular dUrd elevation, indicating thymidylate synthase inhibition.

Observed myelosuppression was comparable to raltitrexed and less than bolus 5-FU.

Conclusions:

ZD-9331 is a potential treatment for solid tumors.
Further clinical trials are warranted to establish its efficacy and optimal dosing.
The safety profile appears manageable, with myelosuppression being the primary dose-limiting toxicity.