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Using of radiochemotherapy improves short-term and long-term results of treatment in patients with primary Hodgkin’s lymphoma (HL) comparing with treatment by chemotherapy alone. The rates of 5-year, 10-year OS and DFS are 88%, 83% and 90%, 86% in case of radiochemotherapy, versus 73%, 66% and 72%, 68% using chemotherapy alone. The 5-year and 10-year OS, DFS estimates in treatment with ABVD are 84% and 83%, 75% and 74%; BEACOPP-baseline - 83% and 82%, 82% and 81% (p<0.05). At the same time ABVD chemotherapy develops less toxicity (p<0.001). The treatment with 6 cycles of ABVD is considered as the most appropriate in primary Hodgkin’s lymphoma patients with extranodal lesions. Comparison of complications rate during chemotherapy with MOPP, ABVD, BEACOPP-baseline, BEACOPP-escalated reveals major hematologic toxicity and infectious complications rate in BEACOPP-escalated program (p<0,05). The age ≥45 years, hemoglobin <105g/l, B symptoms, fibrinogen >5g/l, involvement of 3 and more areas of lymph nodes, liver involvement, inguinal lymph nodes are defined by the multiple-factor analysis as adverse prognostic factors of patients with primary Hodgkin’s lymphoma (HL) with extranodal lesions (p<0.05). Allocation of group of high risk is proved by correlation between survival and the Prognostic Score (PS). The 5-year and 10-year DFS, OS for patients with PS-0-2 estimates are 88% and 86%, 89% and 83%, for patients with PS-3-4 - 78% and 69%, 80% and 77%, for patients with PS-5-6 - 43% and 42%, 60% and 38% respectively (p<0.001).

Gemcitabine is known to exert a therapeutic effect on brain tumors despite the limited permeability of the blood-brain barrier (BBB). In our experimental research single intraperitoneal (i.p.) injection of gemcitabine 25 mg/kg provided increase in median survival of mice with intracranially transplanted Ehrlich carcinoma by 41-89% (p < 0.001). In this experimental model i.p. administration of gemcitabine (permeability of the BBB of less than 10%), carmustine (good permeability of the BBB), cyclophosphamide (poor permeability of the BBB) and cisplatin (doesn't penetrate through the BBB) increased median survival of mice by 88% (p < 0.001), 59% (p = 0.001), 35% (p = 0.005) and 18% (p = 0.302) respectively. Considering strong correlation between antitumor activity of the drugs (carmustine, cyclophosphamide and cisplatin) and their permeability of the BBB, efficacy of gemcitabine in intracranial tumors could be due to its wide range of therapeutic doses.

In a retrospective study during the primary mode MOPP to primary patients LH II/IVAB stages with a poor prognosis rate of CR, 5--and 10-year DFS, OS was 69%, 71% and 68%, 74% and 64%, ABVD--76%, 78%, 83% and 68%, BEACOPP-baseline--73%, 97%, 85% and 82%, respectively. When the program ran BEACOPP-baseline it was revealed higher rates of DFS compared with ABVD and MOPP. Higher OS rates were observed in the primary patients treated with BEACOPP-baseline compared with MOPP (p = 0.04). In terms of DFS and OS MOPP regimen did not differ from ABVD. Program ABVD and BEACOPP-baseline had no differences in terms of OS. The frequency of primary refractory forms of LH did not depend on the conducted regimens of PCT. Significantly less recurrences occurred during the regimen of BEACOPP-baseline compared to MOPP and ABVD. BEACOPP-baseline was accompanied by a more pronounced reversible hematologic toxicity. Against the background of the program BEACOPP-baseline, neutropenia of III-IV degree was detected in 32%, ABVD--16%, MOPP--13%.

The absolute sensitivity signs of breast cancer to the drug have not yet been developed. Data from clinical trials on the study of experimental laboratory predictive markers of chemosensitivity: TOP2alpha (topoisomerase 2-alpha), beta-tubulin (subunit of dimeric protein tubulin), and BRCA1 (breast cancer 1) are contradictory and not numerous. Analysis of the results by the end of the clinical trial will allow examining the correlation between the effectiveness of preoperative taxane-chemotherapy and the level of experimental and standard molecular markets that is important for development of algorithm of treatment tactics for patients with locally advanced breast cancer.

The retrospective study revealed the 15% relapse rate in patients with stage II-IV unfavorable prognosis Hodgkin lymphoma, 5-year OS in relapsed patients was 84%. Karnofsky score less than 80 (p=0,0001), more than 1 extranodal lesion (p=0,0004), extensive (equal to stage III-IV) involvement on relapse (p=0,001), b-symptoms on relapse (p=0,023), more than 5 lymph nodal lesions (p=0,027), albumin level less than 40 g per liter (p=0,037), detection of new nodal lesions (p=0,041) were shown by discriminative analysis as the therapy effect predictors in patients with Hodgkin lymphoma relapse. In patients with second-line therapy failure the actuarial survival rate was lower by 55% in comparison to patients with chemosensitive relapses (40% and 95%). The secondary therapy resistance was shown to be an unfavorable prognosis predictive factor (p=0,0001). The multifactorial overall survival analysis revealed the following adverse prognostic factors: failure of second-line treatment (p=0,0001), first early relapse (p=0,01), albumin level on relapse less than 40 g per liter (p=0,02), use of standard chemotherapy instead of irradiation (p=0,02). The relapse patients with 1 or less risk factors had 95% 5-year OS, the patients with 3 or more adverse risk factors had 70% OS (p=0,0002). The lowest 10-year OS was observed in patients with 2 or more adverse risk factors, 48% and 28% accordingly. Adverse risk factors must be considered while choosing the optimal treatment strategy aimed at better survival rate.

SHR mice with intracranial transplanted lymphosarcoma LIO-1 received a single intraperitoneal gemcitabine injection in maximal tolerated dose of 25 mg/kg or single maximal tolerated oral dose of lomustine, 50 mg/kg. Compared to control group gemcitabine injection increased the mice lifespan 1.4-fold (p < 0,01) and oral lomustine 1.6-fold (p < 0,01). The median lifespan of the mice receiving both gemcitabine and lomustine in maximal dose underwent a significant 3.3-fold increase (p < 0,01) compared to controls (2.4-fold compared to gemcitabine and 2.1-fold compared to lomustine group). Combined therapy didn't cause an increase of toxicity.

In this retrospective clinical study 100 patients with primary unfavorable prognosis stage II Hodgkin lymphoma (HL) (n = 50) or stage IV HL (n = 50). The ABVD chemotherapy allowed to achieve remission in 90% of cases with 5-year relapse-free survival (RFS) and overall survival (OS) of 64% and 92%, the basic BEACOPP regimen lead to the same 90% remission rate with 74% DFS and 94% OS. These results for ABVD and basic BEACOPP regimens are characterized by similar statistic values (p = 1.0; p = 0.6; p = 0.9), although the use basic BEACOPP lead to statically valid decrease of grade III-IV toxicity (p = 0.005). The occurrence of primary refractory HL was slightly higher in basic BEACOPP group (18% versus 10% in ABVD group), although this difference had no statistical value (p = 0.3) and was probably due to higher number of patients with > 1 extranodal localizations. The occurrence of primary refractory HL correlated to disease stage: 6% in stage II and 22% in stage IV (p = 0.04). HL relapse frequency in ABVD and BEACOPP groups was similar (12% and 8%), there was no statistically valid difference (p = 0.5). In ABVD and basic BEACOPP recipients with stage II/IV HL the primary refractory disease rate was 15%, relapse rate was 10%. Five-year OS in primary refractory and relapsed patients was lower, than in general patient population (64% and 70% compared to 80%), although the difference had no statistical significance (p = 0.6, p = 0.7).

Antitumor activity of a new cytostatic drug combination of gemcitabine and dioxadet have been studied in 86 female SHR mice transplanted with 5 x 10(6) of ascitic Ehrlich's tumor cells each. All mice received a single injection of gemcitabine, dioxadet on combination 48 hams after tumor cells introduction. In first series, experimental animals received maximal tolerable dose of gemcitabine (25 mg/kg) and one half of dioxadet maximal tolerable dose (2.5 mg/kg). In the second series of experiments, the animals received 5 mg/kg of dioxadet along with the same gemcitabine dose. Effect of drugs was compared using the time to ascites detection, body weight increase, and survival time. Gemcitabine and dioxadet administered separately and in combination inhibited the growth of ascitic Ehrlich's tumor in the mice. In both series of experiments antineoplastic activity of gemcitabine and dioxadet combination was significantly higher in comparison to the control groups receiving these drugs separately. The highest antineoplastic activity of the gemcitabine and dioxadet combination was observed when the maximal tolerable doses of both drugs was applied. However, the tumor cells growth was also significantly inhibited in mice receiving half of dioxadet dose. Synergism of antitumor activity of gemcitabine and dioxadet was not accompanied by appreciable increase in toxicity.

Efficiency of gemcitabine plus lomustine treatment of transplantable lymphosarcoma LIO-1 in mice was significantly higher than that of monotherapy. According to the area under the kinetic curve for tumor growth, antitumor action, for single maximum tolerable dose of gemcitabine 25 mg/kg body, rose 4.6 times (p < or = 0.001), for lomustine 50 mg/kg body,--2.9 times (p < or = 0.01). The combination involved moderately increased toxicity. Lethality rate for gemcitabine+lomustine, 50 mg/kg body each, was as low as one and a half times as compared with gemcitabine therapy alone, 50 mg/kg body, (30 and 20%, respectively). The antitumor action of the combination (50 mg/kg body), was 32 times that of gemcitabine 50 mg/kg body (p < or = 0.001) and lomustine 50 mg/kg body--30 times (p < or = 0.001).

Retrospective investigation was carried out of clinical course and effectiveness of therapy in 31 patients with primary hepatic involvement in Hodgkin's disease and 63 cases of hepatic lesions relating to dissemination of relapsing tumor. Clinical diagnosis of hepatic involvement ought to be made using at least two procedures, preferably liver scanning and computed tomography of the abdominal cavity. Special attention should be given to most likely cases of specific lesions of liver who had previously presented with intoxication symptoms and spleen and/or subphrenic lymph node involvement. Dissemination-related hepatic lesions were among the most frequent (78%) in patients with primary tumor while focal and diffuse liver involvement was limited to 71% of cases of dissemination of relapsing tumor. MOPP, ABVD and BEACOPP regimes should be given preference in dealing with primary Hodgkin's disease. The latter procedure should predominate in cases of initial extended involvement or as second-line chemotherapy designed to defeat drug resistance and improve end results.

Spinal cord compression was diagnosed in 33 patients with Hodgkin's disease. Specific involvement of the brain was identified in 17 cases of dissemination relapse. Timely use of cytostatic and/or radiotherapy resulted in sustained and complete recovery of the spinal cord. The results in cases of sustained spinal disorders were worse. Tumor-induced specific changes in the brain and spinal cord compression had worse prognosis and median of survival from time of tumor detection was approx. 12 months. In patients with spinal cord compression or cerebral involvement and with concomitant neurologic symptoms, sustained response after chemotherapy with derivatives of nitrosourea (nitrosomethylurea, lomustine and carmustine) (CCNU-OPP, NVPP/NOPP, DVCPP) was (59%) and (64%), respectively. Adequate polychemotherapy with nitrosourea and radiotherapy derivatives and surgery, if required, can improve the efficacy of treatment of Hodgkin's disease patients with spinal cord compression.

Clinical trials were carried out of the protective action of dicarbamin in 33 patients with Hodgkin's disease (13 males and 20 females, average age--31 years). They received standard chemotherapy ABVD (doxorubicin--25 mg/m2, bleomycin--10 mg/m2, vinblastine--6 mg/m2, dacarbazine--375 mg/m2, intravenously, on days 1 and 15 of each cycle, every 4 weeks. Patients suffering neutropenia after the first injection of the cytostatic drugs were given dicarbamin 100 mg/day on day 5 before a second administration. Treatment with dicarbamin continued for 15 days. Its protective effect was reported in 27 patients (81.8%). Leukocyte and granulocyte count before dicarbamin was 3.74 +/- 0.25 x 10(9)/l and 1.42 +/- 0.17 x 10(9)/l, respectively. On completion of the polychemotherapeutic cycle, the indices rose to 5.0 +/- 0.28 x 10(9)/13 and 2.49 +/- 0.25 x 10(9)/l, respectively. The beneficial effect of dicarbamin was also demonstrated by a quick recovery of leukocyte levels than in controls (p > 0.5). After the next cycle of polychemotherapy (ABVD) plus dicarbamin was given for Hodgkin's disease and grade III-IV leuko- and granulocytopenia, leukocyte and granulocyte concentrations returned back to normal which indicated the protective action of dicarbamin.

The efficacy and tolerability of therapy with gemcitabine plus cisplatin were evaluated in 49 patients with disseminated breast cancer refractory to anthracyclines, docetaxel and capecitabine. Gemcitabine 600-750 mg/m2 and cisplatin 30 mg/m2 were injected intravenously, dropwise, on days 1 and 8 of a 3-week course. Overall response rate was 27%; median response duration - 8.0 months, median mediation time until tumor progression--3.2 months, and median survival time--10.3 months. Untoward side-effects were moderate, reversible and, therefore, did not require dosage to be corrected or cut down.

Fifty patients with confirmed local multiple lesions of bone marrow were selected by 99mTc scintigraphy, magnetic resonance imaging and morphologically-supported trepan biopsy from 155 cases of Hodgkin's disease stage II-IVAB. Bone marrow lesions were relatively more common in younger patients 1-11 months after primary tumor detection (an average of 6.5 months). They were detected within 12-156 months (an average of 48 months) among relapsing patients with nodal sclerosis and mixed-cell tumors stage III-IVAB, mostly concomitant with anemia and lymphopenia. Standard combination chemotherapeutical regimens for primary patients (MOPP, ABVD and LOPP) and relapsing ones (CCNU-OPP and ABVD) were effective in those with bone marrow lesions. Side-effects (myelodepression) did not exceed normal levels, provided human recombinant interleukin-1 beta (beta-leukin) was administered for protection and leukopoietic stimulation.

Human recombinant interleukin-1 beta (IL-1beta), administered by intravenous drop infusion, at doses of 10-20 ng/kg daily over 5 days, to a group of 67 patients suffering from malignant tumors and with grade II-IV toxic leukopenia, caused an increase in the leukocyte count to the normal value, within, on average, 8 +/- 1 days. The leukostimulatory effect of IL-1beta, administered subcutaneously at an average dose of 4.6 +/- 0.3 ng/kg (n = 16), appeared to be almost equal to that found for intravenous drop infusion at a dose of 10-20 ng/kg (n = 67). In patients receiving subcutaneous IL-1beta injections, the peripheral blood total leukocyte and granulocyte counts achieved normal values within 9 days. The side effects of IL-1beta at a dose of 0.1-20.0 ng/kg were well tolerated.

The marked and quick response to betaleukin, a preparation of recombinant human interleukin-1 beta, was demonstrated in 77 cases of extensive solid neoplasms and non-Hodgkin's disease, suffering combination chemotherapy-induced toxic leukopenia. Leukopoiesis was effectively stimulated by intravenous administration, of 10-20 ng/kg weight, dropwise for 5 days. Due to adjuvant betaleukin in identical dosage, chemotherapy was continued, in moderate leukopenia, without causing leukocyte count to drop. The untoward side-effects (chiefly. hyperthermia including fever) were reversible and did not hamper treatment.

Clinical studies were carried out in a group of 71 cancer patients to evaluate the effects of intravenous infusion of human recombinant interleukin-1-beta (betaleukin) (I and II phases). It was shown that daily single doses of 10-20 ng/kg body, for 5 days, markedly stimulated leukopoiesis (granulocytopoiesis) in toxic (grade II-IV) leukopenia which hampered combination chemotherapy. A protective effect on leukopoiesis (granulocy-topoiesis) was recorded in cases of moderate leukopenia when chemotherapy was continued. Such side-effects as stage I-III hyperthermia (13.5%) or their combination (50.0%) were effectively managed with paracetamol and antihistamines administration without causing suspension of the drug.