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|Title:||Potentiation of temozolomide in human tumour cells|
|Abstract:||The toxicity of temozolomide, an anti-tumour agent useful in the treatment of various mammalian neoplasms, can be potentiated by the prior administration of an ATase inhibiting agent, i.e., O.sup.6 -benzylguanine.|
|Inventor(s):||Baer; John Colin (London, GB2), Freeman; Azadeh Alison (Croydon, GB2), Newlands; Edward Stuart (London, GB2), Watson; Amanda Jean (Godley Hyde, GB2), Rafferty; Joseph Anthony (Edgeley Stockport, GB2), Margison; Geoffrey Paul (Poynton, GB2)|
|Assignee:||Cancer Research Campaign Technology (Regent's Park, GB2)|
|Filing Date:||Jun 07, 1995|
|Claims:||1. A method of potentiating the toxicity of temozolomide in human cancer cells by administering to a patient in need of such therapy an ATase inhibiting amount of O.sup.6 -benzylguanine and an effective amount of temozolomide. |
2. The method of claim 1 wherein said O.sup.6 -benzylguanine is administered prior to the administration of said temozolomide.
3. The method of claim 1 wherein the dosage administered of said O.sup.6 -benzylguanine is about 1-2000 mg/kg of patient body weight.
4. The method of claim 1 wherein the dosage administered of the O.sup.6 -benzylguanine is 10-800 mg/kg of patient body weight.
5. The method of claim 4 wherein the temozolomide is administered at a rate of 150-300 mgm.sup.-2 of body surface area per day.
6. The method of claim 1 wherein said ATase inhibitor is administered in a dose of 10-800 mg/kg of patient body weight prior to the administration of the temozolomide, said temozolomide is administered in an amount of 150-300 mgm.sup.-2 of body surface area per day, and said O.sup.6 -benzylguanine and said temozolomide are administered in divided doses on consecutive days.
7. The method of claim 6 wherein the total dose of temozolomide is divided into at least four individual doses which are administered on at least four consecutive days.
8. The method of claim 7 wherein said O.sup.6 -benzylguanine is administered two to eight hours prior to the administration of said temozolomide.
9. The method of claim 1 wherein said O.sup.6 -benzylguanine and said temozolomide are administered in divided doses on consecutive days.
10. A method according to claim 1 wherein the human cancer cells are breast cancer tumour cells, astrocytoma tumour cells, colorectal tumour cells, melanoma rumour cells, mycosis fungoides tumour cells or glioma tumour cells.
11. A pharmaceutical composition, for use in treating human cancer cells in a patient in need of such treatment, comprising an effective amount of an O.sup.6 -benzylguanine and an effective amount of temozolomide.
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