PMID: 11919253Mar 29, 2002Paper

Phase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
M J A de JongeJ Verweij

Abstract

To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. Patients were treated with oral ZD9331 given once daily (od) or twice daily (bid) for 5, 7, or 10 days; cycles were repeated every 21 days at doses ranging from 2.5 to 40 mg. For pharmacokinetic analysis, plasma sampling was performed during the first course and assayed using a validated liquid chromatographic-tandem mass spectrometry assay. Plasma levels of 2'-deoxyuridine were measured as a surrogate marker for TS inhibition. Forty-two patients received a total of 166 courses. The DLTs were myelosuppression and skin rash. Dose escalation of oral ZD9331 from 2.5 to 40 mg, as a single daily dose, resulted in a less than proportional increase in the plasma area under the concentration-time curve of ZD9331. The plasma drug exposure per cycle for the schedules 20 mg od for 5 days, 10 mg od for 10 days, and 10 mg bid for 5 days, all resulting in a total dose per cycle of 100 mg, were comparable. One partial response was noted in a patient with gastric cancer. DLTs in this phase I study of oral ZD9331 were myelosuppres...Continue Reading

References

Jan 1, 1995·Annual Review of Biochemistry·C W Carreras, D V Santi
Jan 1, 1994·Advances in Experimental Medicine and Biology·A L JackmanF T Boyle
Jan 1, 1994·Advances in Experimental Medicine and Biology·W AherneA Jackman
Jan 1, 1996·Journal of Cancer Research and Clinical Oncology·Y TakemuraA L Jackman
Mar 28, 1996·International Journal of Cancer. Journal International Du Cancer·Y TakemuraA L Jackman
Nov 1, 1995·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A L Jackman, A H Calvert
Jan 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G LiuE Warner
May 20, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D R BudmanT Griffin
Jun 10, 1998·Cancer Chemotherapy and Pharmacology·P BealeM Walker
Sep 17, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G CocconiS M Hietschold
Mar 7, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·B C GohE Douglass

❮ Previous
Next ❯

Citations

Jan 15, 2004·Cancer Chemotherapy and Pharmacology·Joshua H BilenkerPeter J O'Dwyer
Feb 14, 2003·Current Oncology Reports·W Thomas Purcell, David S Ettinger
Apr 20, 2004·Advanced Drug Delivery Reviews·Ann L JackmanDavid D Gibbs
Jun 4, 2013·Experimental and Molecular Pathology·Sung-Wei LeeYow-Ling Shiue
Dec 19, 2002·Journal of the National Cancer Institute·Sharyn D BakerAlex Sparreboom
Dec 4, 2013·Future Oncology·Raj Kumar Shukla
Feb 14, 2012·Expert Opinion on Investigational Drugs·M MorottiS Ferrero
Jul 11, 2006·British Journal of Clinical Pharmacology·Kong M LiStephen J Clarke
Nov 30, 2002·Expert Opinion on Investigational Drugs·Norman L Lehman
Jul 5, 2003·Lancet·Joseph F Pizzolato, Leonard B Saltz
May 2, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael B SawyerGini F Fleming
Aug 3, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gernot BeutelChris Twelves

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.