Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856).
Edward S. Newlands,George Blackledge,J. A. Slack,Gordon J. S. Rustin,D. B. Smith,N. S. A. Stuart,C. P. Quarterman,R. Hoffman,Malcolm F. G. Stevens,M. H. Brampton +9 more
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In the extended Phase I trial temozolomide only occasionally exhibited the unpredictable myelosuppression seen with mitozolmide, which is easy to use clinically and generally well tolerated.Abstract:
Temozolomide (CCRG 81045: MB 17%) out of 23 patients with melanoma and in one patient with mycosis fungoides (CR lasting 7 months). Two patients with recurrent high grade gliomas have also had partial responses. Temozolomide is easy to use clinically and generally well tolerated. In the extended Phase I trial temozolomide only occasionally exhibited the unpredictable myelosuppression seen with mitozolomide.read more
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Randomized Phase III Study of Temozolomide Versus Dacarbazine in the Treatment of Patients With Advanced Metastatic Malignant Melanoma
Mark R. Middleton,Jean-Jacques Grob,Neil K. Aaronson,G. Fierlbeck,Wolfgang Tilgen,S. Seiter,M. E. Gore,Steinar Aamdal,Jonathan Cebon,Alan S. Coates,Brigitte Dréno,M. Henz,Dirk Schadendorf,Alexander Kapp,Jürgen Weiss,U. Fraass,P. Statkevich,Martin J. Muller,Nick Thatcher +18 more
TL;DR: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.
Journal ArticleDOI
A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse
W. K. A. Yung,Robert E. Albright,Jeffrey J. Olson,R Fredericks,Karen Fink,Michael D. Prados,Michael Brada,Alexander M. Spence,Raymond J. Hohl,William R. Shapiro,Michael Glantz,Harry S. Greenberg,Robert G. Selker,Nicholas A. Vick,R. Rampling,Henry S. Friedman,Peter C. Phillips,Janet M. Bruner,N. Yue,David Osoba,S Zaknoen,Victor A. Levin +21 more
TL;DR: Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 months in the PCB group, and freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received.
Journal ArticleDOI
Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide
Roger Stupp,Pierre Yves Dietrich,Sandrine Ostermann Kraljevic,Alessia Pica,Ivan Maillard,Phillipe Maeder,Reto Meuli,Robert C. Janzer,Gianpaolo Pizzolato,Raymond Miralbell,F. Porchet,Luca Regli,Nicolas de Tribolet,René O. Mirimanoff,Serge Leyvraz +14 more
TL;DR: This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma.
Journal ArticleDOI
Dose Escalation Methods in Phase I Cancer Clinical Trials
TL;DR: Dose escalation methods for phase I trials are reviewed, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents and specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints.
Journal ArticleDOI
Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials
Edward S. Newlands,Malcolm F. G. Stevens,Stephen R. Wedge,Richard T. Wheelhouse,Cathryn S Brock +4 more
TL;DR: This poster presents a poster presented at the 2016 American Academy of Medical Oncology Congress on Wednesday, 3 March 2016 calling for awareness of the importance of informed consent in the selection of patients for cancer treatment.
References
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Journal Article
Antitumor Activity and Pharmacokinetics in Mice of 8-Carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045; M & B 39831), a Novel Drug with Potential as an Alternative to Dacarbazine
Malcolm F. G. Stevens,John A. Hickman,Simon P. Langdon,David Chubb,Lisa M. Vickers,Robert Stone,Ghousia Baig,Colin Goddard,Neil W. Gibson,John Alfred Slack,Christopher Newton,Edward Lunt,Christian Fizames,François Lavelle +13 more
TL;DR: The 3-methyl analogue, 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045), was investigated further and found to possess good activity, when administered i.p. or p.o. to mice bearing the L1210 leukemia.
Journal Article
DNA Sequence Selectivity of Guanine-N7 Alkylation by Three Antitumor Chloroethylating Agents
TL;DR: The DNA sequence selectivities of guanine-N7 alkylation produced by three chloroethylating antitumor agents, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (cis-2-OH CCNU), 2- chlorineoethyl (methylsulfonyl)methanesulfonate and ethyldiazohydroxide, are examined to suggest that the alkylating intermediates,
Journal Article
Phase I clinical trial of mitozolomide.
E. S. Newlands,G. R. P. Blackledge,J. A. Slack,C. Goddard,C. J. Brindley,L. Holden,M. F. G. Stevens +6 more
TL;DR: In the phase I study reported here, a dose of 115 mg/m2 appeared to be safe, but additional studies have shown that when given orally to an older population, most patients experienced thrombocytopenia less than 50,000 cells/mm3.
Journal Article
Effects of the antitumor agent 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one on the DNA of mouse L1210 cells.
TL;DR: In this paper, the authors showed that 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1- d ]-1,2,3,5-tetrazin-4(3 H )-one (MB at equitoxic concentrations, they produced similar levels of DNA interstrand cross-linking.
Journal ArticleDOI
Antitumour imidazotetrazines--XVI. Macromolecular alkylation by 3-substituted imidazotetrazinones.
TL;DR: The results suggest that specific base alkylations rather than total macromolecular alkylation may be more important in determining relative cytotoxicity.
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