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Antitumour herbal medicines based on pink periwinkle and yew tree alkaloids are included in combination therapies for many types of cancer. The use of these classes of products may entail cardiotoxic effects leading to life-threatening conditions. The aim of the study was to analyse scientific literature on cardiotoxic effects of anticancer drugs based on yew tree alkaloids (taxanes) and pink periwinkle alkaloids (vinca alkaloids). The results of the analysis demonstrated that the main manifestations of taxane-induced cardiotoxicity were bradycardia, atrioventricular block, atrial and ventricular arrhythmias. Concomitant use of taxanes and anthracycline antibiotics exacerbated cardiotoxic effects of both drug classes. The use of vinca alkaloids was associated with haematological toxicity in the form of neutropenia, while cardiotoxic effect was rarely observed during monotherapy. Raising awareness among oncologists, cardiologists, and other specialists involved in the management of cancer patients about potential cardiac complications of antitumour therapy contributes to early detection of adverse reactions and allows for individual correction of treatment regimens, especially in patients with predisposition to cardiovascular disease.

Objective: comparative assessment of the economic effect of oral vinorelbine when used as indicated, taking into consideration the new registered price.Material and methods. A clinical-economic study was performed to compare active platinum-containing chemotherapy regimens of the first line for stage IV non-small-cell lung cancer with oral vinorelbine and pemetrexed as well as first-line chemotherapy regimens for metastatic breast cancer presented with oral vinorelbine and ixabepilone alone. A systematic search for information in medical databases was carried out, the cost estimate was made out in accordance with the recommendations of The Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. The direct medical costs were estimated, formed on the basis of the dosage, frequency and dosage regimen of the compared drugs, based on the data of the State Register of maximum selling prices, clinical guidelines for the studied nosologies, and instructions for medical use. The comparison of the economic effect of the studied drugs was carried out in pairs using the cost minimization method with a sensitivity analysis. Further, the calculations of the amounts of reimbursement of medical care provided were made using each of the compared drugs. An economic assessment of the economic effect of oral vinorelbine was carried out taking into consideration the change in the price of the drug and a budget impact analysis with a sensitivity analysis.Results. It was determined that the use of oral vinorelbine provides financial savings for a medical organization at the amount of 246,042.34 rubles per 6 cycles of chemotherapy for each patient with stage IV non-small-cell lung cancer compared with the use of pemetrexed, and 558,659.32 rubles per year – for the treatment of each patient with metastatic breast cancer compared with ixabepilone. The results of the budget impact analysis showed that the indication of oral vinorelbine saved 3,287,470.56 rubles for the budget fund considering the change in the cost of 1 mg of the drug for a hypothetical population of patients with stage IV non-small-cell lung cancer in 1000 people. This would create the possibility of therapy for additional 15 patients with this diagnosis. The indication of oral vinorelbine in first-line chemotherapy of metastatic breast cancer for a similar target population would save 18,355,043.96 rubles for the budget fund, which makes it possible to treat 15 more patients with this diagnosis.Conclusion. The use of oral vinorelbine is associated with the saving of financial resources of a medical organization. In addition, the reimbursement for medical care provided from the compulsory medical insurance funds when using regimens with oral vinorelbine is primarily lower than for comparison drugs. Thus, the use of regimens with oral vinorelbine is more beneficial for the payer (the Federal Compulsory Health Insurance Fund) and for the medical organization. The change in the cost of the drug is associated with an increase in the availability of medical care for patients with stage IV non-small-cell lung cancer and patients with metastatic breast cancer.

Modern therapeutic approaches allow achieving stable therapeutic effect, extension and maximum long-term preservation of the quality of life of metastatic mammary gland cancer patients. Currently there is no optimal consequence of cytostatic agents use. The advantage of using cytostatic peroral forms is related to easiness of their use in clinical practice, no necessity in venopuncture and reduction of need in hospitalization, as well as with the possibility of a more convenient therapy domiciliary. Due to active use of peroral forms of vinorelbine, fluoropyrimidines, methotrexate, cyclophosphamide, ethopozide, patients received a possibility to choose: to remain in the inpatient hospital or to undergo outpatient therapy domiciliary with minimum changes of the style of life.

Drug therapy of disseminated forms of breast cancer involves the use of monoand polychemotherapy with the possible combination with target-therapy in various clinical situations. The article presents the choices of treatment approaches, demonstrated the efficacy and safety of chemotherapeutic regimens on the basis of vinorelbine

Vinca-alkaloids, such as vinblastine, and some of their derivatives, as for example vinorelbine, are widely used in clinical therapy of leukemia and several types of tumors. Their effects are associated with the disfunctioning of the mitotic spindle, which leads to mitosis blockage and a shutdown of the cell cycle. Their primary target is tubulin, however recent research has shown that some of the vinca-alkaloids inhibit calmodulin binding to its targets. Vinka-alkaloids binding with other proteins could be responsible for their efficiency and neuroprotection. Here we investigated the thermodynamics of vinorelbine interactions with calmodulin and tubulin. It was determined that unlike the other vinca-alkaloids both vinorelbine binding sites are located in the C-domain of calmodulin, and characterized by association constants of 4.0 x 10(5) and 5.4 x 10(4) M(-1). At the same time the thermodynamics of vinorelbine binding to tubulin are not much different from that of other vinca-alkaloids. These results will allow getting a better insight on the reaction mechanisms of vinca-alkaloids on a secondary protein target.

The study was concerned with efficacy and tolerability of radiochemotherapy for inoperable non-small cell lung cancer using fractionated single focal dose of radiation in conjunction with vinorelbine or 5-fluorouracil. The treatment proved moderately toxic and was frequently followed by complete regression and survival lasting 12-36 months. Also, it was cost-effective due to shorter courses of radiotherapy.

A total of 59 patients with hormone-resistent prostatic cancer (HDPC) treated in 1999-2004 entered the trial. Three schemes of first-line chemotherapy were examined for clinical efficacy and toxicity in the above patients. Anticancer combined treatment vinorelbin + cycloplatam was given to 23 patients, mitoxantron + prednisolone--to 23 patients, mitoxantron+cysplatin+prednisolone--to 13 patients. The latter scheme was most effect and toxic. Partial regression of metastases and a 50% decrease in the initial PCA level were seen in 23% cases. Vinorelbin+cycloplatam was less effective and toxic: partial regression of metastases--13%, PSA regression-- 17.4%. The least efficacy and toxicity were observed in the treatment with mitoxantron+prednisolone --.7%. Thus, the above first-line HDPC therapy was most effective but has the highest toxicity in using the scheme mitoxantron+cysplatin+prednisolone.

Cycloplatam, a new platinum derivative, evolved at N.S. Kurnakov Institute of General and Inorganic Chemistry in 1982, has been added to the arsenal of Russian cytostatic drugs. Having passed phase I trials, it was approved for treatment of pleural mesothelioma, ovarian carcinoma and multiple myeloma. Leukothrombocytopenia formation indicates toxicity-related limit of dosage. Phase II clinical trials are under way at the Center. They include treatment of solid tumors with cycloplatam alone in urinary bladder tumors, cervical carcinoma and malignant pleurites of various etiology as well as in combination with other cytostatics (carcinoma of the prostate, pleural mesothelioma and urinary bladder tumors). The drug may be recommended both for oral and intracavitary administration; side-effects may include moderate toxicity, chiefly, hematological one.

The efficacy of different antitumor therapies was evaluated in a study involving 53 patients with metastatic breast cancer resistant to anthracyclin antibiotics. Complete and partial regression of tumor was recorded following combined administration of vinorelbin and doxorubicin (27.3%) and taxanes (21.3%). Median therapeutic benefit duration was 22 and 28 weeks, respectively. Response frequency for mitomicin C + mitoxantron + methotrexate regimen was 11.1%. However, no objective therapeutic effects were observed in patients on ifosfamide + mitoxantron and regular 5-fluorouracil infusins.