[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.

[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.

[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.

[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.

[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.

Sensitivity to further endocrine therapy is retained following progression on first-line fulvestrant.

There is a need for new endocrine agents that lack cross-resistance with currently available treatments to extend the endocrine treatment window and delay the need for cytotoxic chemotherapy. This retrospective analysis evaluated the response of postmenopausal patients with previously untreated metastatic/locally advanced breast cancer to further endocrine treatment following progression on first-line fulvestrant or tamoxifen. Patients received fulvestrant 250 mg (intramuscular injection every 28 days) plus matching tamoxifen placebo (once daily), or tamoxifen 20 mg (orally once daily) plus matching fulvestrant placebo (every 28 days) in a double-blind, randomized, phase III trial. Treatment continued until disease progression or withdrawal, when further endocrine therapy was initiated (at the treating physician's discretion). Information regarding subsequent therapies and responses was obtained by follow-up questionnaire. Two-hundred-and-forty-five questionnaires were returned (from 587 patients), 149 of which yielded follow-up data on patients receiving second-line endocrine therapy following fulvestrant (n=83) and tamoxifen (n=66). Second-line therapy produced objective responses (OR) in 6/44 (13.6%) and clinical benefit (CB) in 25/44 (56.8%) patients who had CB with fulvestrant and produced OR in 5/41 (12.2%) patients and CB in 27/41 (65.8%) patients who had CB with first-line tamoxifen. For patients deriving no CB from trial therapy, second-line therapy produced OR in 3/39 (7.7%) and CB in 15/39 (38.5%) patients in the fulvestrant group and OR in 4/25 (16.0%) and CB in 12/25 (48.0%) patients in the tamoxifen group. Results from this questionnaire-based study suggest that postmenopausal women with advanced breast cancer who respond to first-line fulvestrant or tamoxifen retain sensitivity to subsequent endocrine therapy.

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.

[The hemoprotective effect of Dicarbamin in ovarian cancer patients receiving chemotherapy]. / Mekhanizm gemoprotektornogo deistviia dikarbamina u bol'nykh rakom iaichnikov pri provedenii khimioterapii.

The effect of dicarbamin on the hemopoetic cells of the bone marrow of ovarian cancer patients receiving myelosuppressive combination chemotherapy (cyclophosphamide + carboplatin) is discussed.

Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases.

BACKGROUND: This phase III study compared the efficacy of the new potent bisphosphonate, ibandronate, with placebo as intravenous (i.v.) therapy in metastatic bone disease due to breast cancer. PATIENTS AND METHODS: A total of 466 patients were randomised to receive placebo (n = 158), or 2 mg (n = 154) or 6 mg (n = 154) ibandronate every 3-4 weeks for up to 2 years. The primary efficacy parameter was the number of 12-week periods with new bone complications, expressed as the skeletal morbidity period rate (SMPR). Bone pain, analgesic use and safety were evaluated monthly. Results SMPR was lower in both ibandronate groups compared with the placebo group; the difference was statistically significant for the ibandronate 6 mg group (P = 0.004 versus placebo). Consistent with the SMPR, ibandronate 6 mg significantly reduced the number of new bone events (by 38%) and increased time to first new bone event. Patients on ibandronate 6 mg also experienced decreased bone pain scores and analgesic use. Treatment with ibandronate was well tolerated. CONCLUSIONS: These results indicate that 6 mg i.v. ibandronate is effective and safe in the treatment of bone metastases from breast cancer.

[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.

[Surgical treatment of stage III-IV ovarian cancer]. / Khirurgicheskoe lechenie raka iaichnikov III-IV stadii.

A residual tumor after primary cytoreductive surgery is one of the most important factors of survival of patient with advanced ovarian cancer. Maximal cytoreduction can be achieved by different ways. We studied results of extended, combined and standard operations on patients treated in the Russian Cancer Research Center of the Russian Academy of Medical Sciences in 1989-1999. It was found that only optimal cytoreduction resulted in the absence of recurrences and better overall survival of the patients independent of the operation type (extended, combined or standard).