[CDC73 mutations in young patients with primary hyperparathyroidism: A description of two clinical cases]. / Mutatsii v gene CDC73 u molodykh patsientok s pervichnym giperparatireozom (opisanie dvukh klinicheskikh sluchaev).

The article describes two clinical cases of severe primary hyperparathyroidism (PHPT) caused by parathyroid carcinoma in young female patients who underwent molecular genetic testing to rule out the hereditary forms of PHPT. In both patients, heterozygous germline nonsense mutations of tumor suppressor gene CDC73 encoding parafibromin (p.R91X and p.Q166X) were identified using next-generation sequencing with Ion Torrent Personal Genome Machine (Thermo Fisher Scientific - Life Technologies, USA). It is the first description of CDC73 mutations in Russia, one of the mutations is described for the first time in the world. Identification of germline mutations in the CDC73 gene in patients with PHPT necessitates regular lifelong screening for other manifestations of hyperparathyroidism-jaw tumor syndrome (HPT-JT), PHPT recurrence due to parathyroid carcinoma as well, and identification of mutation carriers among first-degree relatives.

[Chemoradiotherapy for locally advanced cervical cancer].

Cervical cancer takes second place in morbidity and third place in mortality from gynecological cancer. Advanced stages among newly diagnosed cases is still large. The "gold standard" of treatment for locally advanced cervical cancer is chemoradiotherapy with cisplatin that results in a lower risk of death. Improvement of radiotherapy methods allowed to bring optimal dose to the primary tumor with the inclusion of regional metastasis areas with less risk of damage to surrounding healthy tissue and organs. The search for alternative combinations of cytostatics, modes of drug administration, adjuvant chemotherapy after chemoradiotherapy showed an increase in survival of patients with locally advanced cervical cancer.

[Pharmacogenomics of cisplatin-based chemotherapy in ovarian cancer patients from Yakutia].

DNA polymorphism is an important component of the interindividual variation in reactions of patients to the same drugs. In this work, evaluation of the association between polymorphisms in 106 genes involved in key processes of cellular activity (xenobiotic metabolism, DNA repair, the cell cycle, and apoptosis), and outcomes in a cohort of Yakut ovarian cancer patients receiving cisplatin-based chemotherapy was carried out. The polymorphism in the CDKN1B gene (rs34330) was found to be associated with complete tumor response and progression-free survival. SNPs in EPXH1 gene (rs2234922 and rs2260863) were correlated with hearing impairment. A SNP in NBN gene (rs1063045) was associated with severe emesis.

[Which patients with ovarian cancer shows the combination of trabectedin with pegylated liposomal doxorubicin].

Given the high rate of recurrence of ovarian cancer, the search for new therapeutic strategies are topical issue. According to various studies the effectiveness of drug treatment relapse depends on the platinum-free interval, increasing in proportion to its duration. If therapy is platinum-resistant recurrent ovarian cancer is a standard approach, the treatment of platinum-sensitive recurrent algorithm is not fully defined. Comparison of platinum and non-platinum combinations revealed the advantage of combined platinum- treatment for patients with platinum-free interval of more than 6 months without an increase in life expectancy. Non-platinum combination of trabected in with pegylated liposomal doxorubicin has shown comparable efficacy with an advantage in overall survival in patients with platinum-free interval of 6-12 months. A platinum-free interval prolongation by the use of non-platinum mode increases the efficiency of subsequent platinum-based therapy, increasing the life expectancy of patients. Currently under study molecular markers and prognostic factors allowing to define a group of patients who have the greatest benefit from the use trabectedin with pegylated liposomal doxorubicin as second-line chemotherapy.

[Current possibilities of targeted therapy in the treatment of breast cancer with overexpression of HER-2/neu and metastatic lesions in the brain].

Targeted therapy (lapatinib and/or trastuzumab) in combination with chemotherapy (capecitabine) is highly effective in metastatic lesions of the brain in breast cancer patients with overexpress HER-2/neu. An objective response in the brain was achieved in 19 patients (55.9%). Complete regression was observed in 5 cases (14.7%), partial regression--14 (41.2%). Stabilization of tumor process in the brain was revealed in 12 patients (35.3%). There was marked improvement in the quality of life of the majority of patients due to the regression of symptoms and good tolerability of treatment.

[Results of combined treatment of patients with metastatic gastric cancer. Case study].

We present the clinical observation of combined treatment of a patient with metastatic gastric cancer. The patient underwent combined chemotherapy for initially inoperable gastric cancer with metastases to the liver, paragastric lymph nodes, and peritoneal carcinomatosis with complete regression of distant metastases, which allowed radical surgery. The patient is currently under regular team observation without signs of disease. His present survival is 44 months.

[CYP2E1 gene polymorphism and ovarian cancer risk in the Yakut population].

The CYP2E1 gene polymorphism has been studied in Yakut women with ovarian cancer and without cancer. The two groups have been found to substantially differ in the frequency of the CYP2E1* 1D allele (with a 96-bp insertion in the promoter region of the gene): it is more frequent in healthy women (16.3 versus 7.4%, P = 0.007).

Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival, surgery, and organ preservation.

BACKGROUND: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points. PATIENTS AND METHODS: These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy. RESULTS: Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030). CONCLUSIONS: In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.

[Combination chemotherapy with newly-developed cytostatics for disseminated small cell lung cancer].

The paper discusses the results of phase II clinical trials of chemotherapy regimens using newly-developed cytostatics for disseminated small cell lung cancer. Taxotere (docetaxel)/cisplatin and campto(irinotecan)/cisplatin were investigated as first-line treatment. Doxorubicin and vincristine in combinations with a novel antitumor cytostatic aranoza were studied for application as second-line treatment. Safety and immediate- and end results were reviewed. Taxotere (docetaxel)/cisplatin and campto(irinotecan)/cisplatin regimens were compared.

[Study on efficacy and toxicity of new combined regimen "taxoter + cisplatin + 5-fluorouracil" in disseminated and locally-spread stomach cancer. Comparative analysis of tolerance and efficacy in patients younger and older than 65 years].

The aim of our study was to evaluate the efficacy and safety of 3-drugs regimen: T 75 mg/m2 d2 + P 75 mg/m2 d2 + F 500 mg/m2 x 3h d 1-3 every 28 days. 31 patients (pts) with morphologically proven advanced gastric cancer of the age 29-77 years (median 61.0) have been treated with this regimen. They received 138 cycles (1-10, median 4.0 cycles per pt). The response rate was evaluated in pts received > or =2 cycles: CR 1/27 (3.7%), PR 12/27 (44.4%), SD 7/27 (25.9%), PD 7/27 (25.9%). The median duration of CR+PR--4.5 mon (1.1-9.9), of SD--6.8 mon (3.0-10.7). Median TTP--5.5 mon. Overall survival: median--11.5 mon, 1-year--46.6%. PS improvement was observed in 54.8%pts, symptomatic improvement--in 71% pts. Toxicity per pt (per cycle) was moderate. There were 11 elderly among these pts. We didn't receive any significant differences in efficacy and severe toxicity in this group compared to non-elderly pts. We observed 55.6% PR, 33.3% SD, 11.1% PD, TTP--4.6 mon, median OS-7.5 mon. in elderly and 5.6% CR, 38.9% PR, 22.2% SD, 33.3 % PD, TTP--6.1 mon, median OS-12.3 mon for non-elderly pts. But dose reduction was performed more frequently in the elderly then non-elderly: 63.6% vs 30.0% pts (p = 0.07) in 64.8% vs 19.1% cycles (p < 0.0001). We consider this regimen to be effective and well tolerated both for elderly and for non-elderly patients.

Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer.

Bone metastases occur in most women with advanced breast cancer and can lead to considerable morbidity and a rapid deterioration in the patient's quality of life. It was the aim of the present study to assess changes in quality of life and bone pain due to intravenous (i.v.) ibandronate, a potent third-generation bisphosphonate. In a phase III randomised, double-blind, placebo-controlled trial in patients with bone metastases due to breast cancer, 466 women were randomised to receive placebo, 2 mg ibandronate or 6 mg ibandronate for up to 96 weeks. Treatment was administered i.v. at 3- or 4-weekly intervals. Clinical endpoints included the incidence of adverse events, quality of life (assessed using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Scale - Core 30 questionnaire (QLQ-C30)), and bone pain (assessed on a 5-point scale from 0=none to 4=intolerable). Ibandronate was generally well tolerated. Compared with baseline measurements, the bone pain score was increased at the last assessment in both the placebo and 2 mg ibandronate groups, but was significantly reduced in the patients receiving 6 mg ibandronate (-0.28+/-1.11, P < 0.001). A significant improvement in quality of life was demonstrated for patients treated with ibandronate (P < 0.05) for all global health status. Overall, at the last assessment, the 6 mg ibandronate group showed significantly better functioning compared with placebo (P = 0.004), and had significantly better scores on the domains of physical, emotional, and social functioning, and in global health status (P < 0.05). Significant improvements in the symptoms of fatigue and pain were also observed in the 6 mg ibandronate group. I.v. ibandronate treatment leads to significant improvements in quality of life, and is an effective and well-tolerated palliative treatment in patients with bone metastases due to breast cancer.

Low titre autoantibodies against recoverin in sera of patients with small cell lung cancer but without a loss of vision.

To date, many authors have described the presence of autoantibodies against various neuronal proteins, paraneoplastic antigens (PNA), in a serum of patients with different kinds of malignant tumors located outside the nervous system. These autoantibodies may cross-react with the corresponding PNA or their epitopes present in neurons and thus initiate the development of a variety of neurological disorders, paraneoplastic syndromes (PNS), even though the primary tumor and its metastases have not invaded the nervous system. Cancer-associated retinopathy (CAR) is a rare ocular PNS induced by autoantibodies against several retinal antigens, one of which is a photoreceptor calcium-binding protein, recoverin. Only several CAR patients with a few kinds of cancer (endothelial carcinoma, breast cancer, epithelial ovarian carcinoma) have so far been found to contain autoantibodies against recoverin in their sera. As for lung cancer, the majority of CAR cases mediated by anti-recoverin autoantibodies have been revealed in patients with the most malignant lung cancer, small cell lung carcinoma (SCLC), and only one similar case has been described for a patient with non-small lung carcinoma. The common feature of all these anti-recoverin-positive patients, irrespective of the type of cancer, is the presence of both the CAR syndrome and high titres (as a rule, more than 1:1000) of the underlying autoantibodies in their serum. In this study, we have used recombinant myristoylated recoverin to screen serum samples of 50 patients with SCLC by Western blot and revealed 5 individuals with low titres of anti-recoverin antibodies, who have no manifestation of a loss of vision. To our knowledge, this is the first report on the presence of low titre autoantibodies against recoverin in a serum of patients with cancer, but without visual dysfunction.

Comparative evaluation of two administration schedules of cis-dichlorodiammineplatinum (DDP) in ovarian and head and neck cancers: a CMEA chemotherapy group study.

The therapeutic effectivity of two administration schedules of DDP were compared. The dose was either 100 mg/m2 infused for 4 h or 20 mg/m2 infused for 1 h on 5 consecutive days. The combined objective remission rate of the two regimens were 37/53 (23% CR ++ 44% PR) for ovarian cancer and 8/35 (9% CR + 14% PR) for head and neck cancer. WHO Grade 1-2 myelo- and nephrotoxicity was observed in 26% and 20%, respectively, out of the 105 cases evaluable for toxicity in the two groups. Nausea and vomiting was moderate to severe. Neither the remission rate nor the toxicity of the two schedules were significantly different.

[Features of chemotherapy of malignant tumors in elderly patients]. / Osobennosti khimioterapii zlokachestvennykh opukholei u patsientov pozhilogo vozrasta.

Elderly patients as a rule have modifications related to age (physiologic changes) and to other concomitant diseases (comorbidity). The glomerular filtration rate decreases with age. Before any chemotherapy is started creatinine clearance should be performed, and the doses of cytotoxic agents with active renal excretion should be modified according to creatinine clearance. Decreased liver blood flow may influence drug disposition. Some changes in liver function do occur with advanced age and may form the basis of some drug toxicities. The lean body mass in elderly people is characterized by an increase in fat, with a decrease in intracellular water, and this change, along with a decrease in serum albumin, can considerably modify drug pharmacokinetics. Decreasing in bone marrow reserve related to age increases the risk of myelotoxicity after cytotoxic therapy. Nevertheless chemotherapy may be tolerable and successful in elderly patients carefully selected. This article contains information about elderly cancer patients treated with cisplatin-based combinations (cisplatin + Vepesid + Nitrullyn, cisplatin + taxotere). There were no serious side effects.

[Experience in treating elderly patients with disseminated stomach and colon cancer]. / Opyt lecheniia pozhilykh bol'nykh disseminirovannym rakom zheludka i tol'stoi kishki.

Colorectal and gastric cancer in usually diagnosed in elderly patients. In metastatic disease systemic chemotherapy has been shown to be of clinical benefit for patients in term of prolongation of survival, symptomatic improvement and quality of life. Compared to its younger counterparts 5-FU-based treatment appears to be equally effective and more toxic according to some reports. Data regarding raltitrexed, oral fluoropyprimidines, Campto or oxaliplatin are limited but suggest no age-specific differences in activity or toxicity. Our experience of using chemotherapy with 5-FU-based combinations, oxaliplatin, Campto, raltitrexed in limited groups of elderly patients confirms this opinion.

[Basic stages of organizing antineoplastic chemotherapy in Russia. Role of the Russian Oncological Scientific Center named for N. N. Blokhina, Russian Academy of Medical Sciences]. / Osnovnye étapy stanovleniia protivoopukholevoi khimioterapii v Rossii. Rol' Rossiiskogo onkologicheskogo naurnogo tsentra im. N. N. Blokhina RAMN.

The paper outlines the history of cancer chemotherapy in our country, starting with the 1950s marked by the first studies made by L. F. Larionov to design cancer chloroethylamine drugs and by studies by N. N. Blokhin who initiated their clinical studies at his headed Institute of Cancer Experimental Pathology and Therapy, USSR Academy of Medical Sciences (now the N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences). The historically established leading role of this center in the development of cancer chemotherapy in Russia is greatly determined by the fact that the country's first specialized department of chemotherapy headed by V. I. Astrakhan was founded in 1960, which has become a center that conducts clinical trials of new Russian and foreign cancer drugs and trains cancer chemotherapeutists. Intensive development of the problem, collaboration with the country's leading research institutions and international cooperation have promoted the development of clinical chemotherapy for cancer diseases, which is an essential component of multimodality treatment in cancer patients now. Alkylating agents, antimetabolites, antitumor antibiotics, taxanes, topoisomerase I and II inhibitors, antiestrogens, antiandrogens, aromatase inhibitors, LH-RH agonists, cytokines. There are prospects for development of basically new approaches to drug therapy for cancer diseases in terms of latest data on the molecular biological features of tumor growth.

[Use of thermal radiochemotherapy in patients with anal epidermoid cancer]. / Primenenie termoradiokhimioterapii u bol'nykh ploskokletochnym rakom anal'nogo kanala.

The authors have developed a new original procedure for combined and multimodal treatment of patients with anal dermoid cancer, which includes radiation therapy, polychemotherapy (platidiam and bleomycin) by using topical superhigh-frequency hyperthermia and antioxidants. The treatment regimen proposed has turned out to be highly effective. It allows sphincter-preserving therapy to be performed without rectal extirpation in most primary patients with anal dermoid cancer.

[Experience with using carminomycin in oncological clinical practice]. / Opyt klinicheskogo primeneniia karminomitsina v onkologicheskoi praktike.

Carminomycin is an original antitumor antibiotic from the anthracycline group isolated at the Institute of New Antibiotics (USSR) in 1973. Pharmacological investigation of carminomycin revealed its satisfactory absorption from the gastrointestinal tract which proved to be a distinguishing property of the antibiotic as compared to other anthracyclines such as adriamycin and rubomycin. The clinical trials of carminomycin showed that it was mainly active against soft tissue sarcoma and breast cancer, lymphosarcoma, neuroblastoma, Wilms' tumor and Ewing's sarcoma in children, as well as acute leukemia. Various regimens for the antibiotic administration were applied: short-term, single and long-term. Suppression of hemopoiesis was considered as a limiting toxic effect. By the data available carminomycin had lower cardiotoxicity as compared with rubomycin and adriamycin. Development of oral carminomycin is believed promising.

[Platinum derivatives in the clinical chemotherapy of malignant tumors]. / Proizvodnye platiny v klinicheskoi khimioterapii zlokachestvennykh opukholei.

Perspectives in clinical chemotherapy with a newly-developed class of compounds - complex derivatives of platinum-are discussed. The history of their development, mechanism of action as well as pharmacokinetics and side-effects of cis-diamminodichloroplatinum are presented. The efficacy of cis-platinum treatment of malignant tumors of the testicle, ovarian and breast carcinoma and other tumors is evaluated on the basis of the literature data and clinical findings of the research staff of the Center.

[Cisplatin (platidiam) and the prospects for using complex platinum compounds in the clinical chemotherapy of malignant tumors]. / Tsiplatin (platidiam) i perspektivy ispol'zovaniia kompleksnykh soedinenii platiny v klinicheskoi khimioterapii zlokachestvennykh opukholei.

The paper discusses the results of combination chemotherapy of 652 patients using platinum derivatives. The treatment proved effective in patients with metastatic tumors (79.7%), ovarian cancer (71.2%) and breast carcinoma (71.2%). Longer survival was obtained in cases of complete regression of ovarian tumor and in effectively treated patients with breast cancer. Response was registered in 30.8% of cases of osteogenic sarcoma. Application of cisplatin in chemoradiation treatment for inoperable bladder cancer resulted in regression of tumor in 57.4%. Literature data on some newly developed platinum derivatives undergoing phase-I and -II clinical trials outside the USSR are discussed.