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Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856).
- Source :
-
British journal of cancer [Br J Cancer] 1992 Feb; Vol. 65 (2), pp. 287-91. - Publication Year :
- 1992
-
Abstract
- 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 dose limiting. Experimentally, temozolomide activity was schedule dependent and therefore oral administration was studied as a daily x 5 schedule between total doses of 750 and 1,200 mg m-2 in 42 patients. Myelosuppression was again dose limiting. The recommended dose for Phase II trials is 150 mg m-2 po for 5 days (total dose 750 mg m-2) for the first course, and if no major myelosuppression is detected on day 22 of the 4 week cycle, the subsequent courses can be given at 200 mg m-2 for 5 days (total dose 1 g m-2) on a 4 week cycle. Mild to moderate nausea and vomiting was dose related but readily controlled with antiemetics. Clinical activity was detected using the 5 day schedule in four (2CR, 2PR; 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Antineoplastic Agents pharmacokinetics
Breast Neoplasms drug therapy
Colorectal Neoplasms drug therapy
Dacarbazine pharmacokinetics
Dacarbazine therapeutic use
Drug Administration Schedule
Drug Evaluation
Female
Glioma drug therapy
Humans
Kidney Neoplasms drug therapy
Male
Melanoma drug therapy
Middle Aged
Neoplasms metabolism
Stomach Neoplasms drug therapy
Temozolomide
Antineoplastic Agents therapeutic use
Dacarbazine analogs & derivatives
Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0007-0920
- Volume :
- 65
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 1739631
- Full Text :
- https://doi.org/10.1038/bjc.1992.57