METHOD PAPA TPATAP PEDÍATP ICO OF HIGH GPADO INCLUDING GLYCOMA OF THE CEREBRAL TRUNK This invention refers to the treatment of certain cancers in children and especially to the treatment of cancers in girls with fcafnopoloraide. The anti-tumor effects of temozolomide are canoed. For example in one study, clinical responses were achieved in 17% of patients with me «; > Advanced Mapping < New3ands ES, et al. Br J Cancer 65 (2) 287-2981, 1992). In another study, a clinical response was achieved in e3 21 of patients with advanced melanoma (Journal af Clinical Oncalagy, Vol 13, No. 4 (April), 1995, pp 910-913). The treatment of "high-grade" glumes in patients with temozal omid, Eur, J. C ncer 1993; 29A: 940. However, the treatment of cancers in children with temozole ida is not well understood. This invention relates to the desirability that ozolomide is effective for the treatment of a very difficult type of skin in children-the high-grade astrocyte, including the brainstem gland. COMPENDIUM OF THE INVENTION This invention can be summarized as a method to treat high grade astrocytoma, including the brain stem, in a child who requires such treatment that he complies with the ozolomide admi sion in an amount sufficient to achieve a clinical response Preferred dosing schemes are presented below. As used herein, the term children and child refers to a human being of an age of 18 years or less. How it is used > - ~ > n the present, the patient term "3 patients?" refers to a child to children. DETAILED DESCRIPTION All references referenced here are incorporated by reference. "Term" temozolomide "refers to a compound that has the formula
A chemical name for temozolamide is 3, 4-d? H? Dra-3- and 11-4, oxoimidazo- (5, 1-d) 1, 2,3,4-te rac? N-8-carba! < imida. 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". This invention contemplates the treatment of these cancers in «any». = > Top of the Discovery "I read cancer until the advanced stage. A person who suffers from high-grade astrocytoma may present one > : > several cl > ^ the following signs or symptoms: ía) presen »:: l« Je cancerous tumor in the brain «D tronco c rebr l. < b) fatigue, () pain, id) state of performance diminished by the tumor burden, and
< e > other symptoms well known as «D« t «a« -Jos with high-grade astracitama including brainstem glioma. In order to practice the invention, temazolamin is administered to the patient who presents one or more of the aforementioned signs or symptoms in an amount sufficient to eliminate or at least mitigate one or more of the signs or symptoms. The preferred dosage of ozolomide for practicing this invention is a total dose of 500 to 1200 mg / m 2 in the patient's body surface, administered for a period of 2 to 28 consecutive days, with a greater degree of preference for a period of 4 to 7 consecutive days, and especially during a period of 5 consecutive days. Therefore, if the total dose should be 1000 mg / m2 administered during a 5-day period, the target dose for this period will be 200 mg / m2. Can daily doses be administered once? to the day after 4 hours of fasting, followed by 2 hours of fasting, which is conventional for temozolomide d. When energetically, temozolomide can be administered more than once a day as shown in our co-pending US patent application.
No (currently identified with lawyer identification number No. 0C626) filed on the same date as this one. After a period of approximately 28 to 42 days, with a greater degree of preference of 28 to 35 days, and specifically of 28 days, as of the first day of the year.; When administering ozol or i da, another administration cycle can be performed with a new administration of temozole ida on day 1 and on each subsequent day of the administration period. As another method of administration, ozalomi te can be administered for a much longer period of time at a reduced dosage. For example, temozolomics could be administered daily for up to 6 to 7 weeks at a dosage of 5 to 100 mg / m2 / day, with a greater degree of preference 75 mg / m2. Temozalomide can be administered orally in the form of capsules where it is mixed with conventional pharmaceutical vehicles. Preferred formulations of emorol capsules are: ingredient mg / capsule temozolo ida 5 20 100 250 lactose anhydrous NF 132.8 182.2 ^?.? 154.3 glycalate> ie sodium starch NF 7.5 11.0 15.0 22.5 colloidal ice diocid NF 0.2 < ") .2 0. 0.7 acid t rt no :) NF 1.5 2.2 3.0 .0 standard acid NF 3. 4.4 6.0 13.5 capsule size * 3 2 1 or
* Capsules "Je hard gelatin of two parts, without« ~ «anservH« i «jr, opaque white color. The cycles of treatment can continue until the pragri- tion of the disease or the appearance of intolerable side effects. The dosage can be "decreased if there are" intolerable side effects or hemotolgic toxicity. A common but tolerable side effect of temozolomide is nausea and vomiting. This can be mitigated by the administration of an antiemetic in combination with the temazolomid. It is preferred that the Ondansetran antiemetic be administered p.o. in the dose of approximately 8 mg approximately 30 minutes before the administration of the temazolomuda. Of course, other antiemetics such as Hasaldol, Benadryl, and Activan can also be used as needed. And, of course, other forms of temozolo ida administration, as available, are contemplated as for example TV injection "-_ infusion, in ratecalmente, in the form of prolonged-release administration, syrup, suppository, administ ion to rans'Jérmica , nasal spray, etc. Any form of administration will work to the extent that ^ > It administers in the proper dosage without destroying the temozalomii. The effectiveness of treatment can be determined through controlled clinical trials. Patients with a cancer treatable by this invention with measurable or evaluable tumors will be included in the study. A measurable tumor is a tumor that can be measured in at least two dimensions. An evaluable tumor is a tumor that can go away in one way. The tumor will be measured or evaluated before and after treatment by any means that provides the most accurate measurement, such as CT scan, MPI scan, et > z. New tumors or the absence thereof in previously irradiated fields can also be used to evaluate the anti-tumor response. The criteria for the evaluation of the response will be similar to those in the WHO Handbook of Cancer Treatment Outcomes, WHO Handbook of Peo- phering Results in Cancer Treatment, WHO Offset Publicatian 1979, 49- World Health Organization, Geneva. The following results are defined for edible tumors um- and bi- imensiap lm nte. Complete answer: Complete disappearance of all the malignant disease línicamente «Jetectable determ? Na« Ja by two observations at an interval not less than 4 week-a. Partial Answer: (a) in the > 3so of the tumors I was able to bidi bially, a decrease of at least 5 < "V." The sum of the pro "Juct" -is "Je 1" os perpendicular major Jiámetrss of all measurable tumors in accordance with that determined by two observations at an interval not less than 4 weeks. ) in the case of tumors that can be measured in a single dimension, a decrease of at least 50% by the sum of the "greater diameters of tumors" as determined by observations at an interval no longer than 4 weeks In cases in which the patient has multiple tumors, it is not necessary that all tumors have returned to achieve a partial response as defined herein, but no tumor should have progressed and no tumor should have appeared stable disease: <a) in the case of idimepsion l med med ib les tumors, less than 50 * i decrease or less than 25 * /. increase in the sum of the products «Je diameters perpendicular "Je tol o tumors medí bles. (b) in the case of multidimensionally mecíb les tumors, a decrease less than 5? 4, ', up to an increment of less than 25' / * in the ..urna '1e lus diameters of all tumors. For (a) and (b) n «- > "New tumors must appear. Progressive disease is ine ".rome? N increase of 25 * /. or more in the product of the greater perpendicular diameters for at least one tumor and 1 medially 1 med med med., or an increase of 25 * /. or more "At least one tumor is measured medically, or the appearance of a new lesion. In the case of the patients who have tumors medically and medically as well as tumors medially and medially, the overall response will be determined according to the following table. Disease response Disease response b id imen ion 1 an idi in iona 1mente Response med ib 1 e me «J ib 1e 9 wolf 1 EP cu l uiera EP any EP EP EE EE or RP EE EE PC P PP EE or PP or PC PP RC EE or RP RP RC RC RC Abbreviations: EP: Progressive Disease PC: Respue s ta Comp le ta ta RP: Partial Response EE: Stable Disease. Obviously the elimination or mitigation of other signs of known symptoms of "high" grade astrocytion, especially those previously listed, can also be used to evaluate the effectiveness of this invention. Cancers should be evaluated, that is, I should go 1"3S tumors, etc. no more than 14 days after the start «Jel treatment. These cancers should be evaluated again 28 days after the "Jia 1" administration of the first dose of ozalomide. 28 days "after the initial administration," another administration and evaluation may be performed. The treatment críelos and the evaluations can continue until the progression of the disease or the appearance of a toxicity "na" zeptable.