CA2184546A1 - Method for treating pediatric high grade astrocytoma including brain stem glioma - Google Patents
Method for treating pediatric high grade astrocytoma including brain stem gliomaInfo
- Publication number
- CA2184546A1 CA2184546A1 CA 2184546 CA2184546A CA2184546A1 CA 2184546 A1 CA2184546 A1 CA 2184546A1 CA 2184546 CA2184546 CA 2184546 CA 2184546 A CA2184546 A CA 2184546A CA 2184546 A1 CA2184546 A1 CA 2184546A1
- Authority
- CA
- Canada
- Prior art keywords
- temozolomide
- high grade
- brain stem
- stem glioma
- grade astrocytoma
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 21
- 208000037564 High-grade astrocytoma Diseases 0.000 title claims abstract description 17
- 206010006143 Brain stem glioma Diseases 0.000 title claims abstract description 15
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229960004964 temozolomide Drugs 0.000 claims abstract description 37
- 230000004044 response Effects 0.000 claims abstract description 15
- 206010028980 Neoplasm Diseases 0.000 description 36
- 201000011510 cancer Diseases 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 5
- 239000002775 capsule Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- DIWRORZWFLOCLC-UHFFFAOYSA-N Lorazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 229940072698 ativan Drugs 0.000 description 1
- 229940088007 benadryl Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 208000011654 childhood malignant neoplasm Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 208000029824 high grade glioma Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000011614 malignant glioma Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229960005343 ondansetron Drugs 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940078646 other antiemetics in atc Drugs 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- -1 transdermal Substances 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
There is disclosed a method for treating high grade astrocytoma, especially brain stem glioma, in a child by administering to a child in need of such treating an amount of temozolomide sufficient to achieve a clinical response. Preferred dosing schedules are provided.
Description
2 18~546 PATENT
METHOD FOR TREATING PEDIATRIC
HIGH GRADE ASTROCYTOMA
INCLUDING BRAIN STEM GLIOMA
This invention relates to the treatment of certain cancers in children and in particular to the treatment of cancers in children with temozolomide Temozolomide is known for its anti-tumor effects. For example, in one study clinical responses were achieved in 17% of patients having advanced melanoma (Newlands ES, et al. Br J Cancer 65 (2) 287-2981, 1992). In another study a clinical response was achieved in 21% of patients with advanced 15 melanoma (Journal of Clinical Oncology, Vol 13, No. 4 (April), 1995, pp 910-913). Treatment of high grade glioma in adults with temozolomide is also known, Eur. J. Cancer 1993; 29A:940. However treating cancers in children with temozolomide is not well known. This invention is predicated on the discovery that temozolomide is effective in treating a very difficult type of cancer 20 in children -- high grade astrocytoma, including brain stem glioma.
SUMMARY OF THE INVENTION
This invention may be summarized as a method for treating high grade 25 astrocytoma, including brain stem glioma, in a child in need of such treatingcomprising administering temozolomide in an amount sufficient to achieve a clinical response. Preferred dosing schedules are listed below.
As used herein the term children and child is intended to mean a human 30 being of age 18 years or less. As used herein the term patient or patients is intended to mean a child or children.
DETAILED DESCRIPTION
All references cited herein are incorporated herein by reference.
The term "temozolomide" is intended to mean a compound having the formula:
21 84~46 O~NH2 N~N
N N~
~1/ CH3 o One chemical name for temozolomide is 3,4-dihydro-3-methyl-4-oxoimidazo-5 [5,1-d]1,2,3,4-tetrazin-8-carboximide. The synthesis of temozolomide is well known. See, for example, Stevens et al., J. Med. Chem, 1984, 27, 196-201 and Wang et al., J. Chem. Soc., Chem. Commun., 1994, pp 1687-1688.
The pediatric cancer treatable by this invention is high grade astrocytoma, including brain stem glioma. This invention contemplates treating this cancers at any stage from the discovery of the cancer to the advanced stage.
A child suffering from high grade astrocytoma may exhibit one or more of the following signs or symptoms:
(a~ presence of cancerous tumor in the brain or brainstem.
(b) fatigue, (c) pain, (d) decreased performance status from tumor burden, and (e) other well known symptoms associated high grade astrocytoma including brainstem glioma.
To practice the invention, temozolomide is administered to the patieQt exhibiting 30 one of more of the above signs or symptoms in an amount sufficient to eliminate or at least alleviate one or more of the signs or symptoms.
~ ~ 1 84546 The preferred dosage of temozolomide for practicing this invention is a total dose of 500 to 1200 mg/m2 of the patient's body surface area, administered over a period of from 2 to 28 consecutive days, more preferable over a period of from 4 to 7 consecutive days, and most preferably over a period5 5 consecutive days. Thus if the tota~ dose is to be 1000 mg/m2 administered over a period of 5 days, the daily dose for this period would be 200 mg/m2.
The daily doses may be administered once per day after four hours of fasting, followed by two hours of fasting, which is conventional for temozolomide.
Alternatively the temozolomide may be administered more than once per day 10 as disclosed in our co-pending U.S. Patent Application No.
(presently identified as attorney's docket no. OC626) filed of even date herewith.
After a period of about 28 to 42 days, more preferably 28 to 35 days, and 15 most preferably 28 days, from the first day of temozolomide administration, another administration cycle may be performed, with temozolomide being re-administered on day one and on each subsequent day of the administration period.
As another administration method, the temozolomide may be administered for a much longer period at reduced dosage. For example, the temozolomide could be administered daily for up to 6 or 7 weeks at a dosage of 50 to 100 mglm21day, more preferably 75 mg/m2.
Temozolomide may be administered orally in capsule form wherein it is admixed with conventional pharmaceutical carriers. Preferred temozolomide capsule formulations are:
Ingredient mg/Capsule temozolomide 5 20 100 250 Anhydrous Lactose NF 132.8 182.2 175.7 154.3 Sodium Starch Glycolate NF 7.5 11.0 15.0 22.5 Colloidal Silicon Diozide NF 0.2 0.2 0.3 0.7 21 845~6 Tartaric Acid NF 1.5 2.2 3.0 9.0 Steric Acid NF 3.0 4.4 6.0 13.5 Capsule Size~ 3 2 1 0 White opaque, preservative-free, two-piece hard gelatin capsules The treatment cycles may be continued until disease progression or 5 intolerable side effects are encountered. The dosage may be decreased, if intolerable side effects or hemotologic toxicity are encountered.
A common, but tolerable side effect of temozolomide is nausea and vomiting. This can be alleviated by administering an anti-emetic in conjunction 10 with the temozolomide. It is preferred that the anti-emetic Ondansetron be given p.o. in a dose of about 8 mg about 30 minutes before temozolomide administration. Of course other anti-emetics such as Hasaldol, Benadryl, and Ativan may also be used as needed.
Of course, other forms of administration of temozolomide, as they become available, are contemplated, such as by IV injection or infusion, intrathecally, by sustained release dosage form, syrup, suppository, transdermal, nasal spray, etc.. Any form of administration will work so long as the proper dosage is delivered without destroying the temozolomide.
The effectiveness of treatment may be determined by controlled clinical trials. Patients having a cancer treatable by this invention with measurable or evaluable tumors will be included in the study. A measurable tumor is one that can be measured in at least two dimensions. An evaluable tumor is one that 25 can be measured in one dimension.
The tumor will be measured or evaluated before and after treatment by whatever means provides the most accurate measurement, such as CT scan, MRI scan, etc. Newtumorsorthe lackthereof in previously irradiated fields 30 can also be used to assess the anti-tumor response. The criteria for-evaluating response will be similar to that of the WHO Handbook of Reporting Results of Cancer Treatment, WHO Offset Publication 1979, 49-World Health ~ ~5~ ;~ 1 84546 Organization, Geneva. The following results are defined for uni- and bi-dimensionally measurable tumors.
Complete response: Complete disappearance of all clinically detectable 5 malignant disease determined by two observations not less than four weeks apart.
Partial Response: (a) for bidimensionally measurable tumors, a decrease of at least 50% in the sum of the products of the largest perpendicular10 diameters of all measurable tumors as determined by two observations not lessthan four weeks apart. (b) for unidimensionally measurable tumors, a decrease by at least 50% in the sum of the largest diameters of all tumors as determined by two observations not less than four weeks apart. In cases where the patient has multiple tumors, It is not necessary for all tumors to have regressed to 15 achieve a partial response as defined herein, but no tumor should have progressed and no new tumor should appear.
Stable disease: (a) for bidimensionally measurable tumors, less than a 50% decrease to less than a 25% increase in the sum of the products of the 20 largest perpendicular diameters of all measurable tumors. (b) for unidimensionally measurable tumors, less than a 50% decrease to less than a 25 % increase in the sum of the diameters of all tumors. For (a) and (b) no new tumors should appear.
Progressive disease is defined as an increase of 25% or greater in the product of the largest perpendicular diameters for at least one bidimensionally measurable tumor, or an increase of 2~ % or greater at least one unidimensionally measurable tumor, or appearance of a new lesion.
For patients having both uni- and bi-dimensionally measurable tumors, the overall response will be determined in accordance with the following table.
Response in Response in bidimensionally unidimensionally measurable disease measurable disease Overall Response PD any PD
Any PD PD
SD SD or PR SD
SD CR PR
~ 21 84546 PR SD or PR or CR PR
CR SDorPR PR
CR CR CR
Abbreviations: PD: Progressivé Disease CR: Complete Response PR: Partial Response SD: Stable Disease Of course elimination or alleviation of other known signs or symptoms of high grade astrocytoma, especially those listed previously, can also be used to evaluate the effectiveness of ~his invention.
The cancers should be evaluated, i.e. tumors measured, etc., no more than 14 days before the start of the treatment. These cancers should be reevaluated about 28 days after day 1 of administration of the first dose of temozolomide. Twenty eight days after this initial administration another 15 administration and evaluation may be performed. The treatment cycles and evaluations may be continued until disease progression or unacceptable toxicity is encountered.
METHOD FOR TREATING PEDIATRIC
HIGH GRADE ASTROCYTOMA
INCLUDING BRAIN STEM GLIOMA
This invention relates to the treatment of certain cancers in children and in particular to the treatment of cancers in children with temozolomide Temozolomide is known for its anti-tumor effects. For example, in one study clinical responses were achieved in 17% of patients having advanced melanoma (Newlands ES, et al. Br J Cancer 65 (2) 287-2981, 1992). In another study a clinical response was achieved in 21% of patients with advanced 15 melanoma (Journal of Clinical Oncology, Vol 13, No. 4 (April), 1995, pp 910-913). Treatment of high grade glioma in adults with temozolomide is also known, Eur. J. Cancer 1993; 29A:940. However treating cancers in children with temozolomide is not well known. This invention is predicated on the discovery that temozolomide is effective in treating a very difficult type of cancer 20 in children -- high grade astrocytoma, including brain stem glioma.
SUMMARY OF THE INVENTION
This invention may be summarized as a method for treating high grade 25 astrocytoma, including brain stem glioma, in a child in need of such treatingcomprising administering temozolomide in an amount sufficient to achieve a clinical response. Preferred dosing schedules are listed below.
As used herein the term children and child is intended to mean a human 30 being of age 18 years or less. As used herein the term patient or patients is intended to mean a child or children.
DETAILED DESCRIPTION
All references cited herein are incorporated herein by reference.
The term "temozolomide" is intended to mean a compound having the formula:
21 84~46 O~NH2 N~N
N N~
~1/ CH3 o One chemical name for temozolomide is 3,4-dihydro-3-methyl-4-oxoimidazo-5 [5,1-d]1,2,3,4-tetrazin-8-carboximide. The synthesis of temozolomide is well known. See, for example, Stevens et al., J. Med. Chem, 1984, 27, 196-201 and Wang et al., J. Chem. Soc., Chem. Commun., 1994, pp 1687-1688.
The pediatric cancer treatable by this invention is high grade astrocytoma, including brain stem glioma. This invention contemplates treating this cancers at any stage from the discovery of the cancer to the advanced stage.
A child suffering from high grade astrocytoma may exhibit one or more of the following signs or symptoms:
(a~ presence of cancerous tumor in the brain or brainstem.
(b) fatigue, (c) pain, (d) decreased performance status from tumor burden, and (e) other well known symptoms associated high grade astrocytoma including brainstem glioma.
To practice the invention, temozolomide is administered to the patieQt exhibiting 30 one of more of the above signs or symptoms in an amount sufficient to eliminate or at least alleviate one or more of the signs or symptoms.
~ ~ 1 84546 The preferred dosage of temozolomide for practicing this invention is a total dose of 500 to 1200 mg/m2 of the patient's body surface area, administered over a period of from 2 to 28 consecutive days, more preferable over a period of from 4 to 7 consecutive days, and most preferably over a period5 5 consecutive days. Thus if the tota~ dose is to be 1000 mg/m2 administered over a period of 5 days, the daily dose for this period would be 200 mg/m2.
The daily doses may be administered once per day after four hours of fasting, followed by two hours of fasting, which is conventional for temozolomide.
Alternatively the temozolomide may be administered more than once per day 10 as disclosed in our co-pending U.S. Patent Application No.
(presently identified as attorney's docket no. OC626) filed of even date herewith.
After a period of about 28 to 42 days, more preferably 28 to 35 days, and 15 most preferably 28 days, from the first day of temozolomide administration, another administration cycle may be performed, with temozolomide being re-administered on day one and on each subsequent day of the administration period.
As another administration method, the temozolomide may be administered for a much longer period at reduced dosage. For example, the temozolomide could be administered daily for up to 6 or 7 weeks at a dosage of 50 to 100 mglm21day, more preferably 75 mg/m2.
Temozolomide may be administered orally in capsule form wherein it is admixed with conventional pharmaceutical carriers. Preferred temozolomide capsule formulations are:
Ingredient mg/Capsule temozolomide 5 20 100 250 Anhydrous Lactose NF 132.8 182.2 175.7 154.3 Sodium Starch Glycolate NF 7.5 11.0 15.0 22.5 Colloidal Silicon Diozide NF 0.2 0.2 0.3 0.7 21 845~6 Tartaric Acid NF 1.5 2.2 3.0 9.0 Steric Acid NF 3.0 4.4 6.0 13.5 Capsule Size~ 3 2 1 0 White opaque, preservative-free, two-piece hard gelatin capsules The treatment cycles may be continued until disease progression or 5 intolerable side effects are encountered. The dosage may be decreased, if intolerable side effects or hemotologic toxicity are encountered.
A common, but tolerable side effect of temozolomide is nausea and vomiting. This can be alleviated by administering an anti-emetic in conjunction 10 with the temozolomide. It is preferred that the anti-emetic Ondansetron be given p.o. in a dose of about 8 mg about 30 minutes before temozolomide administration. Of course other anti-emetics such as Hasaldol, Benadryl, and Ativan may also be used as needed.
Of course, other forms of administration of temozolomide, as they become available, are contemplated, such as by IV injection or infusion, intrathecally, by sustained release dosage form, syrup, suppository, transdermal, nasal spray, etc.. Any form of administration will work so long as the proper dosage is delivered without destroying the temozolomide.
The effectiveness of treatment may be determined by controlled clinical trials. Patients having a cancer treatable by this invention with measurable or evaluable tumors will be included in the study. A measurable tumor is one that can be measured in at least two dimensions. An evaluable tumor is one that 25 can be measured in one dimension.
The tumor will be measured or evaluated before and after treatment by whatever means provides the most accurate measurement, such as CT scan, MRI scan, etc. Newtumorsorthe lackthereof in previously irradiated fields 30 can also be used to assess the anti-tumor response. The criteria for-evaluating response will be similar to that of the WHO Handbook of Reporting Results of Cancer Treatment, WHO Offset Publication 1979, 49-World Health ~ ~5~ ;~ 1 84546 Organization, Geneva. The following results are defined for uni- and bi-dimensionally measurable tumors.
Complete response: Complete disappearance of all clinically detectable 5 malignant disease determined by two observations not less than four weeks apart.
Partial Response: (a) for bidimensionally measurable tumors, a decrease of at least 50% in the sum of the products of the largest perpendicular10 diameters of all measurable tumors as determined by two observations not lessthan four weeks apart. (b) for unidimensionally measurable tumors, a decrease by at least 50% in the sum of the largest diameters of all tumors as determined by two observations not less than four weeks apart. In cases where the patient has multiple tumors, It is not necessary for all tumors to have regressed to 15 achieve a partial response as defined herein, but no tumor should have progressed and no new tumor should appear.
Stable disease: (a) for bidimensionally measurable tumors, less than a 50% decrease to less than a 25% increase in the sum of the products of the 20 largest perpendicular diameters of all measurable tumors. (b) for unidimensionally measurable tumors, less than a 50% decrease to less than a 25 % increase in the sum of the diameters of all tumors. For (a) and (b) no new tumors should appear.
Progressive disease is defined as an increase of 25% or greater in the product of the largest perpendicular diameters for at least one bidimensionally measurable tumor, or an increase of 2~ % or greater at least one unidimensionally measurable tumor, or appearance of a new lesion.
For patients having both uni- and bi-dimensionally measurable tumors, the overall response will be determined in accordance with the following table.
Response in Response in bidimensionally unidimensionally measurable disease measurable disease Overall Response PD any PD
Any PD PD
SD SD or PR SD
SD CR PR
~ 21 84546 PR SD or PR or CR PR
CR SDorPR PR
CR CR CR
Abbreviations: PD: Progressivé Disease CR: Complete Response PR: Partial Response SD: Stable Disease Of course elimination or alleviation of other known signs or symptoms of high grade astrocytoma, especially those listed previously, can also be used to evaluate the effectiveness of ~his invention.
The cancers should be evaluated, i.e. tumors measured, etc., no more than 14 days before the start of the treatment. These cancers should be reevaluated about 28 days after day 1 of administration of the first dose of temozolomide. Twenty eight days after this initial administration another 15 administration and evaluation may be performed. The treatment cycles and evaluations may be continued until disease progression or unacceptable toxicity is encountered.
Claims (16)
1. A method for treating high grade astrocytoma in a child in need of such treating comprising administering temozolomide in an amount sufficient to achieve a clinical response.
2. The method of claim 1 wherein the amount of temozolomide administered is from 500 to 1200 mg per m2 of the patient's body surface area administered over a period of from 2 to 28 days.
3. The method of claim 2 wherein the temozolomide is administered over a period of from 4 to 7 days.
4. The method of claim 3 wherein the temozolomide is administered over a period of 5 days.
5. The method of claim 2 wherein after a period of 28 to 42 days after the first day of the temozolomide administration period, the temozolomide administrations are repeated.
6. The method of claim 4 wherein after a period of 28 days after the first day of the temozolomide administration period, the temozolomide administrations are repeated.
7. The method of claim 1 wherein the temozolomide is administered daily for at least 6 weeks at a dosage of 50 to 100 mg/m2/day.
8. The method of claim 7 wherein the dosage of temozolomide is 75 mg/m2/day.
9. the method of claim 1 wherein the high grade astrocytoma is brain stem glioma.
10. the method of claim 2 wherein the high grade astrocytoma is brain stem glioma.
11. the method of claim 3 wherein the high grade astrocytoma is brain stem glioma.
12. the method of claim 4 wherein the high grade astrocytoma is brain stem glioma.
13. the method of claim 5 wherein the high grade astrocytoma is brain stem glioma.
14. the method of claim 6 wherein the high grade astrocytoma is brain stem glioma.
15. the method of claim 7 wherein the high grade astrocytoma is brain stem glioma.
16. the method of claim 8 wherein the high grade astrocytoma is brain stem glioma.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US69907196A | 1996-07-31 | 1996-07-31 | |
| US08/699,071 | 1996-07-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2184546A1 true CA2184546A1 (en) | 1998-02-01 |
Family
ID=24807802
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2184546 Abandoned CA2184546A1 (en) | 1996-07-31 | 1996-08-30 | Method for treating pediatric high grade astrocytoma including brain stem glioma |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPH1045590A (en) |
| CA (1) | CA2184546A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000057867A3 (en) * | 1999-03-30 | 2001-04-19 | Schering Corp | Improved cancer treatment with temozolomide |
-
1996
- 1996-08-30 CA CA 2184546 patent/CA2184546A1/en not_active Abandoned
- 1996-09-02 JP JP23239596A patent/JPH1045590A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000057867A3 (en) * | 1999-03-30 | 2001-04-19 | Schering Corp | Improved cancer treatment with temozolomide |
| AU780892B2 (en) * | 1999-03-30 | 2005-04-21 | Merck Sharp & Dohme Corp. | Improved cancer treatment with temozolomide |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH1045590A (en) | 1998-02-17 |
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