Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856).

@article{Newlands1992PhaseIT,
  title={Phase I trial of temozolomide (CCRG 81045: M\&B 39831: NSC 362856).},
  author={Edward S. Newlands and George R. P. Blackledge and John A. Slack and G. J. S. Rustin and D. B. Smith and Nicholas S. A. Stuart and Charmaine Paulina Quarterman and Richard Hoffman and Malcolm Francis Graham Stevens and M. H. Brampton},
  journal={British Journal of Cancer},
  year={1992},
  volume={65},
  pages={287 - 291}
}
Temozolomide (CCRG 81045: M&B 39831: NSC 362856) is an analogue of mitozolomide displaying similar broad spectrum activity in mouse tumours, but showing considerably less myelosuppression in the toxicology screen. Temozolomide was initially studied intravenously at doses between 50-200 mg m-2 and subsequently was given orally up to 1,200 mg m-2. A total of 51 patients were entered on the single dose schedule. Temozolomide exhibits linear pharmacokinetics with increasing dose. Myelotoxicity was… 
Phase I trial of temozolomide using an extended continuous oral schedule.
TLDR
Toxicity was greatest in higher dose cohorts, with a resultant maximum tolerated dose of 85 mg/m2/day, whereas lower dose cohorts tolerated the schedule well, and the area under the temozolomide plasma versus time curve was noncumulative between the first and last week of the schedule.
Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer.
  • M. Dhodapkar, J. Rubin, +5 authors V. Suman
  • Medicine
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1997
TLDR
It is concluded that TMZ is well tolerated in this oral 5-day schedule with dose-limiting thrombocytopenia and that it has promising activity in glioma and melanoma.
A phase II study of Temozolomide in advanced untreated pancreatic cancer
TLDR
Toxicity was primarily hematological with 3 patients experiencing ≥ grade 3 neutropenia and thrombocytopenia respectively and other toxicities were relatively modest.
A phase I trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood.
TLDR
A phase I trial to determine the maximum tolerated dose (MTD) of temozolomide given in combination with lomustine in newly diagnosed pediatric patients with high-grade gliomas found one patient with a 5-mm enhancing nodule postoperatively had a complete response, one patients with a large residual temporal lobe glioblastoma had a partial response, and eight patients had stable disease.
Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies
TLDR
When given orally once daily for 5 days, temozolomide was well tolerated and produced a non-cumulative, transient myelosuppression, the most common non-haematological toxicities were mild to moderate nausea and vomiting.
Phase I study of O6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors.
  • K. Warren, A. Aikin, +4 authors F. Balis
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2005
TLDR
The combination of O6BG and TMZ was tolerable at TMZ doses less than half of the conventional dose of 200 mg/m2/d, which is recommended in children with solid tumors.
Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.
TLDR
Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose, and the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle.
A Phase I and pharmacokinetic study of temozolomide and cisplatin in patients with advanced solid malignancies.
TLDR
The toxicities, recommended dose, and pharmacological profile of the TMZ/CDDP combination are determined and the recommended doses for Phase II clinical trials are TMZ 200 mg/m2/day for 5 days with 75 mg/ m2 CDDP on day 1, every 4 weeks.
A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse
TLDR
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.
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