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    Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer
    (Springer, 2012) Yildiz, Ramazan; Benekli, Mustafa; Ozkan, Metin; Alkis, Necati; Berk, Veli; Kaplan, Mehmet Ali; Ciltas, Aydin
    The efficacy and tolerability of bevacizumab every 2 or 4 weeks using the same dosage in combination with biweekly FOLFIRI were retrospectively evaluated in metastatic colorectal cancer (mCRC) patients in the first-line and second-line therapy. A total of 332 patients from six centers were evaluated. The patients had received biweekly FOLFIRI in combination with bevacizumab 5 mg/kg every 2 weeks or every 4 weeks schedule for various reasons in individual patients. Approximately 70 % of all patients had 2-week treatment schedule. In the first-line therapy (n = 240), the overall response rate (ORR) was 34.1 % in 2-week and 36.3 % in 4-week groups. Median progression-free survival (PFS) was 8 months (95 %CI, 6.8-9.2) and 9 months (95 %CI, 6.6-11.4) (p = 0.074), and median overall survival (OS) was 22 months (95 %CI, 15.8-28.2) and 20 months (95 %CI, 8.1-31.9) (p = 0.612) in 2- and 4-week groups, respectively. One-year survival rate was 76.2 % for 2-week group and 73.2 % for 4-week group. In the second-line therapy (n = 92), the ORR was similar between the groups (24.5 vs 25.9 % in 2- and 4-week groups, respectively). Median PFS was 6 months (95 %CI, 4.7-7.3) and 11 months (95 %CI, 6.3-15.7) (p = 0.074), and median OS was 15 months (95 %CI, 9.6-20.4) and 17 months (95 %CI, 13.7-20.3) (p = 0.456) for 2-week and for 4-week groups, respectively. One-year survival rate was 61.3 % for 2-week and 71.3 % for 4-week groups. Toxicity profile was similar in 2- and 4-week groups and included neutropenia, febrile neutropenia, nausea and vomiting, diarrhea, mucositis, bleeding, hypertension, thromboembolism and fistulization. Bevacizumab 5 mg/kg every 2 weeks or every 4 weeks in combination with biweekly FOLFIRI had similar efficacy and tolerability in mCRC. Because of the retrospective nature of our study, the data should be examined cautiously. However, our study clearly points out the need for determination of optimum biological dosing interval of bevacizumab in well-designed, prospective, randomized trials.
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    Clinicopathological Features in Bilateral Breast Cancer
    (Asian Pacific Organization Cancer Prevention, 2012) Baykara, Meltem; Ozturk, Selcuk Cemil; Buyukberber, Suleyman; Helvaci, Kaan; Ozdemir, Nuriye; Alkis, Necati; Berk, Veli
    Introduction and Purpose: The frequency of bilateral breast cancer is 1.4-11.0% among all breast cancers. It can present as synchronous (SC) or metachronous (MC). Data regarding clinical course of bilateral breast cancer are scarce. In this study, we therefore evaluated demographic, pathological and clinical characteristics, treatments and responses in bilateral breast cancer cases; making distinctions between metachronous-synchronous and comparing with historic one-sided data for the same parameters. Materials and Methods: One hundred fifty bilateral breast cancer cases from ten different centers between 2000 and 2011 were retrospectively scanned. Age of the cases, family history, menopausal status, pathological features, pathological stages, neoadjuvant, surgery, adjuvant and palliative chemotherapy/radiotherapy were examined in the context of the first and second occurrence and discussed with reference to the literature. Results: Metachronous and synchronous groups showed similar age, menopausal status, tumor type, HER2/neu expression; the family history tumor grade, tumor stage, ER-negativity rate, local and distant metastases rates, surgery, adjuvant chemotherapy application rates were identified as significantly different. Palliative chemotherapy response rate was greater in the metachronous group but median PFS rates did not differ between the groups. Conclusion: Although bilateral breast cancer is not frequent, MC breast cancer is different from SC breast cancer by having more advanced grade, stage, less ER expression, more frequent rates of local relapse and distant metastasis and better response to chemotherapy in case of relapse/metastasis.
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    A cross-sectional survey of the diagnosis and management of bone metastasis in breast cancer patients in Turkey
    (Springer, 2014) Arican, Ali; Bozkurt, Tulin; Bozcuk, Hakan; Demirkan, Binnaz; Buyukberber, Suleyman; Alkis, Necati; Sanli, Ulus Ali
    This study aimed to report the practice of managing breast cancer with bone metastasis in Turkey and to determine the adherence to the British Association of Surgical Oncology (BASO) guidelines. This multicenter, cross-sectional epidemiological survey was conducted in 38 centers across Turkey. Data from 1,026 breast cancer patients with bone metastases (mean age 54.0 +/- 11.9 years) were analyzed. Over 30 % of patients had a diagnosis of metastatic breast cancer (stage IV) at the time of primary diagnosis. The imaging modalities used for diagnosing bone metastases were bone scintigraphy (57.8 %), radiography (22.8 %), and bone survey (4.4 %). Tumor markers were detected in 94.9 %, and markers of bone metabolism were measured in 90.4 % of patients. A total of 3.5 % of patients underwent surgery for bone metastasis, 26.4 % underwent palliative chemotherapy (most commonly docetaxel + capecitabine), and 56.5 % endured radiotherapy. Most patients (96 %) also received bisphosphonate. Radiography, bone scintigraphy, and CT were the main imaging tools used for postoperative follow-up of bone metastasis. Our results were > 95 % in line with the BASO guidelines for the management of bone metastasis, except that interventional procedures, such as biopsy, were applied less frequently in our survey. The diagnosis and management practices of breast cancer with bone metastasis in Turkey were generally compatible with international guidelines. However, the awareness and knowledge of physicians on the current guidelines should be increased, and equipment for the appropriate interventional procedures should be provided in every clinic to obtain optimal and standard management of bone metastases.
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    The efficacy and toxicity of irinotecan with leucovorin and bolus and continuous infusional 5-fluorouracil (FOLFIRI) as salvage therapy for patients with advanced gastric cancer previously treated with platinum and taxane-based chemotherapy regimens
    (Maney Publishing, 2012) Kaya, Ali Osman; Coskun, Ugur; Gumus, Mahmut; Dane, Faysal; Ozkan, Metin; Isikdogan, Abdurrahman; Alkis, Necati
    There is no established standard salvage chemotherapy in the second-line setting for patients with advanced gastric cancer (AGC) pre-treated with platinum and taxane-based chemotherapy. Our study aims to evaluate the safety and efficacy of FOLFIRI regimen (irinotecan with leucovorin and bolus and continuous infusion with 5-fluorouracil) as a salvage chemotherapy regimen in patients with AGC. Medical records of 97 patients with AGC who received second-line FOLFIRI regimen between March 2006 and February 2011 were examined. Complete and partial responses were observed in 3 (3.1%) and 23 (23.7%) patients, respectively. The median time to progression (TTP) was 3.5 months (95% CI: 2.4-4.6) and the median overall survival (OS) was 10.5 months (95% CI: 8.8-12.2). The most common observed grade 3/4 toxicities were neutropenia (23.7%), diarrhea (6.2%), and stomatitis (5.2%). FOLFIRI regimen is safe and effective in the second-line treatment of AGC patients pre-treated with cisplatin and taxanes.
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    Outcome of non-metastatic male breast cancer: 118 patients
    (Humana Press Inc, 2012) Arslan, Ulku Yalcintas; Oksuzoglu, Berna; Ozdemir, Nuriye; Aksoy, Sercan; Alkis, Necati; Gok, Ayse; Kaplan, Mehmet Ali
    Studies concerning adjuvant systemic therapy and prognosis in male breast carcinoma (MBC) are limited. We aimed to evaluate outcome of the changing practices of adjuvant systemic treatment and survival in operable MBC patients over the last two decades. The medical records of 148 MBC patients followed between the years 1986 and 2009 at 7 cancer center were evaluated retrospectively. One hundred and eighteen operable non-metastatic patients had sufficient data were included the study. One hundred and eighteen operable MBC were found to be eligible. Median age was 60 (range 29-83) years. Thirty-two percent of the patients had T3-4 tumors. Half of the patients had axillary lymph node-positive disease. The proportion of positivity of estrogen receptor(ER), progesterone receptor (PgR), and HER2 status were 82.9, 75.8, and 23.4%, respectively. Only, 7 patients had triple negative (TN). Adjuvant hormonotherapy was advised for 76.8% whereas adjuvant chemotherapy for 73.7% of the patients. Median follow-up was 40.9 months (range 3.8-186 months). Locoregional and/or distant recurrence developed in thirty-eight patients (32.2%). Twenty-three patients died during the follow-up period. Five-year disease-free survival (DFS) was found to be 60%, whereas overall survival (OS) was 82%. Larger tumor size and lymph node positivity were statistically significant poor prognostic factors for OS. Although statistical insignificant, patients with HER2-positive tumors have worse DFS (52 vs. 120 months, log rank P = .73) and OS (85 vs. 144 months, log rank P = .30) than HER2-negative ones. Although the frequency of the use of adjuvant systemic therapy in MBC has been increasing and survival rates improving for the last decades, lymph node status and tumor size are still the most important determining factors for prognosis. There is a need for further prognostic information in men with HER2-positive or TN breast cancer.
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    Prognostic Factors and Treatment Outcomes in 93 Patients with Uterine Sarcoma from 4 Centers in Turkey
    (Asian Pacific Organization Cancer Prevention, 2012) Durnali, Ayse; Tokluoglu, Saadet; Ozdemir, Nuriye; Inanc, Mevlude; Alkis, Necati; Zengin, Nurullah; Sonmez, Ozlem Uysal
    Introduction: Uterine sarcomas are a group of heterogenous and rare malignancies of the female genital tract and there is a lack of consensus on prognostic factors and optimal treatment. Objective and Methodology: To perform a retrospective evaluation of clinicopathological characteristics, prognostic factors and treatment outcomes of 93 patients with uterine sarcomas who were diagnosed and treated at 4 different centers from November 2000 to October 2010. Results: Of the 93 patients, 58.0% had leiomyosarcomas, 26.9% malignant mixed Mullerian tumors, 9.7% endometrial stromal sarcomas, and 5.4% other histological types. According to the last International Federation of Gynecology and Obstetrics (FIGO) staging, 43.0% were stage I, 20.4% were stage II, 22.6% were stage III and 14.0 % were stage IV. Median relapse free survival (RFS) was 20 months (95% confidence interval (CI), 12.4-27.6 months), RFS after 1, 2, 5 years were 66.6%, 44.1%, 16.5% respectively. Median overall survival (OS) was 56 months (95% CI, 22.5-89.5 months), and OS after 1, 2, 5 years was 84.7%, 78%, 49.4% respectively. Multivariate analysis showed that age >= 60 years and high grade tumor were significantly associated with poor OS and RFS; patients administered adjuvant treatment with sequential chemotherapy and radiotherapy had longer RFS time. Among patients with leiomyosarcoma, in addition to age and grade, adjuvant treatment with sequential chemotherapy and radiotherapy after surgery had significant effects on OS. Conclusion: Uterine sarcomas have poor progrosis even at early stages. Prognostic factors affecting OS were found to be age and grade.
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    Prognostic factors for teenage and adult patients with high-grade osteosarcoma: an analysis of 240 patients
    (Humana Press Inc, 2013) Durnali, Ayse; Alkis, Necati; Cangur, Sengul; Yukruk, Fisun Ardic; Inal, Ali; Tokluoglu, Saadet; Seker, Mehmet Metin
    The aim of this retrospective, multicenter study was to evaluate clinicopathological characteristics, prognostic factors and treatment outcomes of teenage and adult patients with high-grade osteosarcoma. A total of 240 osteosarcoma patients who were diagnosed and treated from March 1995 to September 2011 were analyzed. Median age was 20 years (range 13-74 years), and 153 patients (63.8 %) were male. Primary tumor localization was extremity in 204 patients (85.4 %), trunk in 21 patients (8.8 %) and head and neck region in 14 patients (5.9 %). According to American Joint Committee on Cancer staging system, 186 patients (77.5 %) were stage II, 3 (1.3 %) were stage III and 48 (20.0 %) were stage IV. Median overall survival (OS) was 55 months (95 % CI 36.8-73.1 months). OS after 2, 5 and 10 years were 67, 49 and 42 %, respectively. Univariable analysis for OS showed that male gender (p = 0.032), high baseline lactate dehydrogenase (LDH) level (p < 0.001), high baseline serum alkaline phosphatase level (p = 0.002), telangiectatic subtype (p = 0.023), presence of metastasis at diagnosis (p < 0.001), presence of tumor positive margins after primary surgery (p = 0.015), poor pathological response to preoperative chemotherapy (p = 0.006) and presence of recurrent disease during follow-up period (p < 0.001) were significantly associated with poor survival. Patientswho received postoperative methotrexate plus doxorubicin plus cisplatin (M + A + P) combination regimen (p = 0.019), underwent surgery for recurrent disease (p < 0.001) and received chemotherapy for recurrent disease (p < 0.001) had longer OS. Inmultivariable analysis for OS, only high LDH level (p = 0.002) and the presence of metastasis at diagnosis (p = 0.011) were associated with poor OS, whereas the patients who received chemotherapy for recurrent disease had a longer OS (p = 0.009).
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    Retrospective evaluation of premenopausal hormone-sensitive breast cancer patients treated with adjuvant gonadotropin-releasing hormone analogue.
    (Lippincott Williams & Wilkins, 2014) Demirci, Ayse; Alkis, Necati; Dane, Faysal; Yazilitas, Dogan; Durnali, Ayse; Inanc, Mevlude; Ozcelik, Melike
    [Abstract Not Available]
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    Retrospective evaluation of premenopausal hormone-sensitive breast cancer patients treated with adjuvant gonadotropin-releasing hormone analogue: Anatolian Society of Medical Oncology (ASMO) study
    (Wiley, 2018) Demirci, Ayse; Alkis, Necati; Dane, Faysal; Durnali, Ayse; Yazici, Omer Kamil; Rzayev, Rashad; Kaya, Serap
    AimThe goal of this study is to evaluate possible factors affecting the survival of patients treated with gonadotropin-releasing hormone (GnRH) analogues. MethodsDemographic characteristics, treatment modalities, overall survival (OS) and the possible factors affecting the survival a total of 554 premenopausal breast cancer patients in Turkey evaluated retrospectively. ResultsThe median duration of GnRH analogues use was 2213.6 (range, 1-87) months. Patients were divided into three groups according to the duration of GNRH analogues use; 4-12 months (Group A), 13-24 months (Group B) and 25 months (Group C). Overall, 530 patients were analyzed; 23.2%, 45.8%, 30.9% of the patients were in Group A, B and C, respectively. The median follow-up duration was 34 +/- 30.3 (range, 4-188) months. The OS in patients 35 years of age was found to be significantly longer than that of patients >35 years of age in Group B (log rank, P = 0.023). The disease-free survival of the patients in Group A was significantly shorter than that of patients in Group C (log rank, P = 0.003). The OS of Group A patients was significantly shorter in comparison to that of Group B and Group C patients (log rank, P = 0.000) and the OS of Group B patients was significantly shorter than Group C (log rank, P = 0,000). ConclusionThere is currently no definite data on the optimal duration of GnRH analogues use. One of the important results of this study that will provide an insight to the future studies is the improvement gained in OS by the increase in the duration of GnRH analogues use.