[Combined effect of gemcitabine and lomustine in mice with intracranial transplanted lymphosarcoma LIO-1].

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.

[Relapse in Hodgkin lymphoma].

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.

[Primary refractory and relapsed Hodgkin lymphoma with unfavorable prognosis].

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).

[Primary-refractory forms of Hodgkin's lymphoma].

Retrospective analysis defined risk factors of primary-refractory course of Hodgkin's lymphoma as well as adverse prognostic factors, efficacy of I and II therapy lines in patients with primary-refractory forms of Hodgkin's lymphoma. By means of discriminant analysis risk factors were as follows: massive tumor lesion, chemotherapy as compared to chemoradiotherapy in the I line, intoxication symptoms, IPS > or = 3, LDH level more than 1,5xULN, late beginning of specialized treatment (over 12 months from initial symptoms of disease), damage of 5 and more areas of lymph nodes, age more than 45 years, increase of ESR higher than 30 mm/h in Stage B and 50 MM/H in Stage A, Stage IV of disease, leukocyte rate higher than 15 x 10(9)/l, presence of more than one extranodal lesion. As a result there were revealed 4 prognostic factors unfavorably influencing on survival rates in primary-refractory forms of Hodgkin's lymphoma with originally Stages II/IV with poor prognosis. The worst 5-year survival rates were found in the presence of 3 and 4 adverse prognostic factors. These circumstances should be taken into consideration choosing optimal treatment and predicting of success of the proposed treatment.

[Investigation of gemcitabine plus lomustine treatment in mice with transplantable lymphosarcoma LIO-1].

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).

[Synergism of antitumor activity of gemcitabine and dioxadet in mice with ascitic Ehrlich's tumor].

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.