Glioblastoma multiforme (GBM) makes up as many as 30% of all primary brain tumors. Despite the employment of multimodal antitumor treatment, the overall survival is less than one year. Between 06/01/1998 and 06/01/2000 17 patients (Group A) with GBM (11 males, 6 females; median age 54.3 years) were administered local chemotherapy with cisplatin incorporated into biodegradable 6-carboxylcellulose polymer (cisplatin-depot (CDDP-D)). After the subtotal removal of GBM, twenty 1.5 x 1.5 cm polymer plates with a total area of 45 cm2 (the density of cisplatin immobilization on 6-carboxylcellulose being 1 mg/cm2, a total cisplatin dose of 45 mg) were implanted into the tumor bed. Group B (21 patients with GBM; 11 males, 10 females; median age 53.2 years) was control: the subtotal tumor ablation without CDDP-D implantation. Two to three weeks after the surgery all the patients of Groups A and B started a course of radiation therapy. A total dose of cranial irradiation was 20 Gy (1 fraction/day, 5 days/week; a daily dose of 2 Gy) followed by a boost tumor bed irradiation (1 fraction/day, 5 days/week; a daily dose of 2 Gy) up to the conventional dose of 60 Gy. Survival data for the patients were processed using the Kaplan-Meier method and analyzed by logrank test. All the patients of Group A tolerated surgical ablation of the brain tumor without side effects (brain edema, seizures, etc.). No patient of Group A had a reduction in blood cell counts during six weeks that would indicate systemic exposure to cisplatin. Blood chemistry and urinalysis did not show evidence of renal injury. No side effects of radiotherapy were registered in Group B either, regarding both the psychoneurological status of the patients and the basic values of homeostasis. Karnofsky performance scale (KPS) score of Group A and Group B patients demonstrated no significant differences before and after the surgery. The median overall survivals for patients of Group A and Group B were 427.5 and 211.0 days respectively (p = 0.00001; overall logrank test). Conclusion. Local chemotherapy of GBM with CDDP-D followed by irradiation is well tolerated and effective.

No abstract

The possibility of determining baclofen in the anionic and cationic forms has been investigated. The main analytical characteristics of a cation-selective electrode reversible to baclofen were determined. A rapid potentiometric technique for baclofen determination in pills without long and laborious sample preparation is proposed.

A simple method for isolating temozolomide, which is used to treat several types of malignant tumors, from its dimethylsulfoxide (DMSO) solvate was investigated. The method consisted of treating temozolomide DMSO solvate with a refluxing Me 2 CO:H 2 O mixture. It was found that decreasing the H 2 O content in the mixture and reducing the reflux time improved the purity of the final product. The best result was obtained by refluxing the sample in anhydrous Me 2 CO. The reproducibility of the proposed method was demonstrated. It was established that the size of temozolomide crystals obtained by this method was much smaller than after recrystallization from aqueous Me 2 CO.Keywords: temozolomide, dimethylsulfoxide solvate.Temozolomide (I, 4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide) is an imidazotetrazine heterocyclic compound that possesses antitumor activity and is used to treat malignant gliomas and melanomas and other malignant tumors [1]. Compound I is stable in acidic solution (pH < 5) and labile in basic solution (pH > 7). Therefore, it can be used perorally. Compound I hydrolyzes spontaneously at physiological pH values to give 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide and then fragments to 5-aminoimidazole-4-carboxamide and methyldiazonium cation. The latter is a methylating agent with respect to DNA [2 -4]. A convenient method for synthesizing I is cycloaddition of methylisocyanate to 5(4)-diazoimidazole-4(5)-carboxamide, which in turn is obtained from 5(4)-aminoimidazole-4(5)-carboxamide (Scheme 1) [5 -7]. The reaction is carried out in dimethylsulfoxide (DMSO). The isolated product requires additional purification in order to be used as a drug. Thus, we observed during reproduction of the described method that I was isolated as its DMSO solvate with a I:DMSO mole ratio of 1:1. However, the product without DMSO is used in medical practice.Compound I can be isolated from the solvate by recrystallization from aqueous Me 2 CO. However, large volumes of solvents must be used because of its poor solubility. A method for purifying I by rinsing with aqueous Me 2 CO was also described [6]. This method consisted of several sequential steps of treating the solvate with Me 2 CO, H 2 O, and again with Me 2 CO. A drawback of this method was the number of operations.The goal of the present study was to develop an improved method for isolating I from its DMSO solvate. EXPERIMENTAL PARTThe DMSO solvate of I was prepared by the literature method [8]. 398 0091-150X/14/4806-0398