No 18 (2012)

The article describes the main problems associated with currently used anticancer chemotherapy. The main groups of cytotoxic drugs and details of their mechanism of action are presented. General concepts of promising modern method of anticancer therapy, an application of polymer derivatives of medicines, are explained. Polymeric compounds can alter the pharmacokinetics of drugs and increase their blood circulation time due to high molecular weight. This improves the efficiency of the capture of polymeric derivatives by tumor cells, which are characterized by increased endocytosis in contrast to normal cells. The characteristics of polymers (polycations, polyanions and neutral polymers) used for the transport systems of selective drug delivery are discussed. The features of the development of micellar delivery systems and vaccination type systems represented by the classical Ringsdorf model are determined.

Bone complications of prostate cancer are serious problem faced by both patients and clinicians. Prevention of bone complications remains one of the major challenges for oncourologists. With the advent of new drugs, treatment options are gradually extending; furthermore, effectiveness of the treatment also increases. The use of bisphosphonates, particularly zoledronic acid, is the treatment of choice for the prevention of bone complications in patients with prostate cancer. However, the high efficacy of denosumab in prevention of bone complications and its effect on the tumor process gives the way for thinking about the preferability of treatment.

The article presents the results of evaluation of the effectiveness of EGFR inhibitors erlotinib and gefitinib, an anti-VEGF monoclonal antibody bevacizumab in non-small cell lung cancer (NSCLC). 86 patients received EGFR inhibitors. Objective response (OR) was 18,8 %, tumor growth control (TGC) - 60 %. The median time to progression (MTTP) was 5.3 months, median overall survival (MOS) - 13.3 months. Mutations in the 19th and 21st exons of the EGFR gene were found in 31.6% of cases: deletion in 19th exon (23,7 % and L858R substitution in 21st exon of the EGFR gene (7,9 %. MTTP in patients with EGFR mutations was 13,8 months, in patients without mutations - 2,7 months (p = 0,05); MOS in patients with mutations in EGFR - 21,3 months, and without a mutations - 6,8 months (p = 0,5). The study that examined the efficacy of bevacizumab in combination with standard chemotherapy regimens included 135 patients. OR in the group paclitaxel + carboplatin without bevacizumab was 20 %, with bevacizumab - 43,3 %; MTTP - 4 vs 7 months, MOS - 9,1 vs 15,6 months, respectively (p = 0,00036). A similar comparative analysis was performed for the regimen gemcitabine + cisplatin in combination with or without bevacizumab. OR in the group without bevacizumab was 24 %, with bevacizumab - 47 %. MTTP was 5 vs 7 months (p = 0,023), the MOS - 7,8 vs 15,8 months, respectively (p = 0,00085). Tyrosine kinase inhibitors are effective in NSCLC, but their administration is justified mainly in the case of mutations in EGFR. The addition of bevacizumab to standard chemotherapy improves outcomes in patients with NSCLC.

From 1990 to 2008, in the Department of Surgery of Tumors of the Liver and Pancreas FSBI “ROSC named after N.N. Blokhin RAMS”, 527l iver resections of various sizes for metastases of colon cancer were performed; 41 of them were re-resection. 356 patients received postoperative chemotherapy: 137 patients received the adjuvant treatment with combination of fluorouracil and leucovorin, 193 - with combination of oxaliplatin, fluorouracil and leucovorin (FOLFOX). The remaining 26 patients underwent another chemotherapy. Liver resection in combination with perioperative regional FOLFOX chemotherapy ± bevacizumab was performed in 106 cases. The study showed the feasibility and effectiveness of adjuvant chemotherapy after liver resection for metastases of colorectal cancer. Adding oxaliplatin to postoperative chemotherapy has improved the results of combined treatment. The use of bevacizumab improves the efficacy of regional neoadjuvant therapy without significant improvement of long-term results.

Endocrine therapy is important component in the treatment of receptor-positive metastatic breast cancer (RPBC), and allows achieving good results with low toxicity of treatment. When hormonal therapy should be administered, it is necessary to consider the level of Ki-67 and HER2-status in addition to clinical data. The most effective first-line drugs include aromatase inhibitors (non-steroidal and steroidal), fulvestrant, tamoxifen. If first-line treatment is effective, transition to the second and subsequent lines of hormone therapy is appropriate. A number of studies have shown high treatment effect with adding targeted agents: trastuzumab or lapatinib + aromatase inhibitor for HER2 overexpression in the first line; gefitinib +anastrozole in first-line hormonal therapy of advanced RPBC, everolimus + exemestane or tamoxifen in the second-line hormonal therapy.

Chemotherapy of head and neck squamous cell carcinoma of the (HNSCC) has taken a worthy place in the treatment regimens of locally advanced primary neoplastic processes, and in the treatment of relapses and distant metastases. Modern treatment regimens for locally advanced HNSCC require timely and adequate incorporation of the entire arsenal of chemotherapy effective in this type of tumors. In particular, the use of induction chemotherapy with taxanes, drugs that provide the highest locoregional control, is justified. The use of targeted therapy, including drug cetuximab, has expanded our therapeutic options in the treatment of locally advanced neoplastic processes and provides the high efficiency of 1st line chemotherapy in recurrent HNSCC and distant metastases.

In patients with hormone-sensitive breast cancer and clinical or biochemical signs of ovarian estrogen synthesis, the use of aromatase inhibitors is contraindicated. Pre- and posttreatment measurement of estradiol and follicle-stimulating hormone levels should be performed in women receiving aromatase inhibitors, who are not clearly postmenopausal, or have the risk of resumption of ovarian function. The uses of tamoxifen in perimenopausal women, suppression of ovarian function (SOF) or a combination of POF with tamoxifen remain the standard adjuvant hormonal therapy strategies.