e15519 Background: Metronomic therapy (MT) is one of the most promising advances in cancer treatment strategy focused on both tumor cells and their microenvironment, specifically anti-angiogenic, immune and metabolic regulation. The treatment modality is a durable cytostatic drugs exposure with less toxicity. We investigated the efficacy of MT in point of prolonged duration of response (more than 6 months) in pts with the advanced resistant tumors. Methods: A total of 678 pts have been enrolled in the study and have been treated MT cyclophosphamide 50 mg (qd, PO) and methotrexate 2.5 mg (BID, PO) twice per week dosing schedule until progression. 508 pts (75%) had disease progression during first 6 months. Long-term efficacy (more than 6 months) was assessed in 170 pts (25%). The study population characteristics were female 122 (72%) vs male 48 (28%). Among the enrolled pts median age was 70 years (range from 37 to 91 years). ECOG status ranged from 0 to 4 (median - 1). The majority of pts received MT as a 2nd and 3rd line (57%) of the therapy (range from 1 to 11): 1-2 – 106 (62%), 3-4 - 52 (31%), 5 and more - 12 (7%). The distribution of pts by diagnosis is presented in the table 1. The majority of MT pts were represented by advanced clinical stage III-IV (97,6%): I - 1 (0,5%), II - 3 (2%), III - 7 (4%), IV - 159 (93,5%). MT commonly used in early-stages cancer in elderly patients with multiple comorbidities contraindicated to standard treatment. Most pts had two or multiple metastatic sites. Results: The ongoing long-term effect for MT indication was from 6 to 46 months. The main group consisted of the breast and colorectal cancer, 27% and 15%, respectively. The median time to progression was 9 months (16 months in CR was achieved (0,4%), 11 months and 9 months with a partial response (3,4%) and stable disease (21,2%), respectively). 12 (1,7%) pts are on ongoing long-term follow up more than 24 months. MT was well-tolerated. Drug related adverse events were described upon the study: hematological (10,2%, Gr 3-4 – 3,5%) vs non-hematological (6,6%, Gr 3-4 1,7%) toxicity. Conclusions: MT schedule demonstrated effectiveness in patients with advanced resistant tumors. The median duration of the effectiveness doesn’t depend on the line of therapy, tumor localization and objective response. The role of possible predictive markers of clinical benefit is question of further trials. [Table: see text]
e13005 Background: Gemcitabine has a very modest potency to penetrate blood-brain barrier (BBB). So far it's therapeutic activity in intracranial tumors is unknown. Methods: we explored the effect of gemcitabine (G) on overall survival in models of intracranial Ehrlich's tumor and lymphosarcoma LIO-1. As a comparison for the investigation group we've chosen drugs with different ability to penetrate into brain. We injected BCNU (50 mg/kg), cyclophosphamide (C) (150 mg/kg) and CDDP (9 mg/kg) intraperitoneally once 24 hours after transplantation. Results: The mean overall survival (OS) of mice in a selected model is 9,6+/-0,4 days. The injection of G resulted in substantial increase in OS up to 16,2 +/-0,4 (69%, p = 0,0000). In comparative groups administration of BCNU resulted in an increase in OS of 49% (the average OS 14,3+/-0,8, p = 0.000289), C - in 20% OS increase (11,5+/-0,4, p = 0.00272) and CDDP did not influence OS comparing with control group (10,2+0,4 days, p = 0.315). In other experiment mice with intracranial transplantated lymphosarcoma LIO-1 lived 15.4+1.3 days after single i.p. administration of G (25 mg/kg in 24 hours after transplantation) in comparison with 11.2+0.4 days in control group. The absolute increase of life expectancy was 37.5% (p = 0.013). In control group at 14 day after the transplantation all animals died whereas in G group only 3 mice out of 10 (30 %, g = 0.0003) died. Single i.p. administration of 25 mg/kg G on the 5th day after the intracranial transplantation of LIO-1, increased average OS of the animals from 10,9+ 0,4 days in control group to 13.5±0.5 days (increase in OS 24%, p = 0.0003). Conclusions: In our series of experiment we showed the potency of gemcitabine in treatment of various intracranial tumors. Until our work we can not find any data obtained on efficacy of gemcitabine in this tumor types.
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