Systemic and intrapleural chemotherapy for metastatic tumor pleurisy was carried out in cats with breast carcinoma. The animals (n=18) were divided into 2 groups. Cats of the systemic chemotherapy group received 3-6 courses of taxotere (30 mg/m(2); n=7) or 3 courses of taxotere (20 mg/m(2)) in combination with doxorubicin (20 mg/m(2)at 21-day intervals (n=5) during the adjuvant period of therapy for metastatic tumor pleurisy. Objective effect was attained in 10 (84.6%) cats: partial remission in 3 (25%) and complete remission in 7 (58.3%, p>0.05) cats. Metastatic pleurisy progressed in 2 (16.7%) cats. The median time to progression reached 1.79 months, median lifespan 2.8 months. The animals of intrapleural chemotherapy group (n=6) received 1-4 courses of cyclophosphamide (250 mg/m(2)) at 1-week interval during the adjuvant period without therapy for malignant pleurisy. Malignant pleurisy progressed in all cats. The median time to progression was equal to median lifespan (0.6 months). The therapy for malignant pleurisy in cats with breast cancer is regarded as the second-line chemotherapy with taxotere preferable as a monotherapy or in combination with doxorubicin.
Modeling of a transarterial chemoembolization (TACE) is carried out on rats (n = 6) with hepatocellular cancer of liver RS1 (Vcp = 4.5 cm3) which has developed in muscles of the leg (i.m.). Sensitivity of a tumor to the single introduction of substance of doxorubicine (sDOX) in maximum tolerated doses (MTD) of 5-12 mg/kg with the achievement of significantly tumor growth inhibition on 55-77% (p = 0.001) is previously shown. TACE is executed with the elastic polyvinyl alcohol microspheres in size of 0.2 mm in diameter loaded with doxorubicine (MS/sDOX) with the release within 7 days. MS/sDOX in the volume of 0.034-0.1 ml (a cumulative dose of sDOX of 3.3-10.5 mg/kg) was introduced into a femoral artery (i/a) with a diameter of 0.16 mm under control of an embolization (MS or arterial ligature) and chemotherapy (sDOX). TACE gave rise in the cytoreductive effect of the tumor nodule by 67% (T/C = 33%, p = 0.0004) with the single regression and the development of the grade 1 therapeutical pathomorphosis (TP). The therapeutic gain of MC/sDOX manifested in coupled with the cytoreduction the decline of the tumor growth rate («т» = 11-16 against 1.9-2.0 days in the control group) and at the equal inhibiting action with sDOX dose reduced by 20% against MTD. Side effects of TACE (a necrosis of soft tissues, 7th-16th days) were not associated with the full stagnation of a regional blood flow due to the discrepancy of MS to diameter of the artery. The whole of the revealed effects has allowed to consider the modeling of i/m tumor on rats to be suitable for the screening of the specific activity of agents clients for TACE. The preclinical study of the method is rational to execute on the corresponding model on large animals with regional artery of the sufficient cross section of the vessel permitting to perform TACE satisfactory.
The research is devoted to the study of the efficacy of new Russian microspheres loaded by (MC/DOX) of 0.4-0.6 mm diameter on a basis of cryogel with poly(vinyl alcohol) intended for a transarterial chemoembolization (TACE). MC/DOX in dose of of 0.5-1.0 ml contained Doxorubicin of 16 mg or 32 mg were transarterially injected in a single dose to rabbits (n = 24) with the VX2 anaplastic carcinoma of the moderate volume of 3-5 cm2 which developed in femur muscles (the pool of a femoral artery). The time of complete released of DOX was 16 days up to dose (a cumulative dose) 16 and 32 mg, respectively. The efficacy was controlled with the decrease of the tumor growth rate and significant inhibition through embolization of turnpike blood of a tumor zone under radiological monitoring. MC/DOX were shown both to give rise in the regression of tumor nodes and reduce the growth rate by 2.0-2.5 times in dependence on the dose value. The reliable therapeutic prize of MC/DOX against embolization effect of 0.5 ml MC that achieved at the maximal DOX cumulative dose of 32 mg consists in the achievement of regression of VX2 up to 50% at 5 of 6 rabbits with the development of the cure pathomorphological effect of III degree which is characterized by the gain in the area of a necrosis by 1.5-3.0 times. The maximal efficient cumulative dose of 32 mg Doxorubicin exceeds value of Maximum Planned Dose (MPD) of Doxorubicin by 6 times for systemic injection to rabbits. The embolizing effect of MC/DOX in the form of blocking of shallow arterioles at preservation of turnpike blood supply did not depend on the size of the applied dose. The reliable antineoplastic effect revealed on this model allows good out perspective for a transarterial chemoembolization of a tumor with MC/DOX.
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