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ABSTRACT: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration.
Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5' UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms.
Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population.
Pharmacogenetics might contribute to tailored therapy.
Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(4):1553-6. · 0.66 Impact Factor
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Yuksel Urun,
Nuriye Yildirim Ozdemir,
Gungor Utkan,
Hakan Akbulut,
Berna Savas,
Berna Oksuzoglu,
Derya Gokmen Oztuna,
Izzet Dogan,
Bulent Yalcin,
Filiz Cay Senler,
Handan Onur, Ahmet Demirkazik,
Nurullah Zengin,
Fikri Icli
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ABSTRACT: Background: Previous studies have observed an association between ABO blood group and risk for certain gastrointestinal malignancies, including pancreatic and gastric cancer. However, it is unclear whether there is such an association with colorectal cancer (CRC). In this study, possible relationships between ABO blood groups and Rh factor and KRAS status in patients with CRC were investigated. Materials and Methods: In 1,620 patients with CRC, blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of the Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with wild type K-ras status was also evaluated. Results: Overall distributions of ABO blood groups as well as Rh factor were comparable between patients (45% A, 7.2% AB, 16.4% B, 31.4% O, and 87.2% Rh+) and controls (42.2% A, 7.6% AB, 16.3% B, 33.9% O, and 87.7% Rh+) (p=0.099). However, there were statistically significant difference between patients and controls with respect to O vs. non O blood group (p=0.033) and marginally significant difference for A vs. non-A blood group (p=0.052). Among patients, the median age was 62 (range 17-97), 58.1% were male. There were no statistically significant differences respect to sex and K-ras status. Conclusion: In present study, the ABO/Rh blood groups were statistically significantly associated with the risk of CRC. There were no relationship between K-ras status and ABO blood group and Rh factor. However further studies with larger numbers of patients are needed to establish the role of blood groups and to define the mechanisms by which ABO blood type affect CRC.
Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(12):6097-100. · 0.66 Impact Factor
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Mutlu Dogan,
Lutfi Dogan,
Feyyaz Ozdemir,
Nuriye Yildirim Ozdemir,
Hasan Senol Coskun,
Ulku Yalcintas Arslan,
Guze Ozal,
Gungor Utkan, Ahmet Demirkazik,
Fazil Aydin,
Nurullah Zengin,
Fikri Icli
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ABSTRACT: Kaposi sarcoma (KS) is a mesenchymal tumor originating from lymphatic endothelial cells. Immunosuppressive patients have higher risk for KS. HHV-8 has a role in immunopathogenesis of KS. Aim Evaluation of demographical properties with tumor characteristics and treatment modalities of KS.
Histopathologically documented KS patients were evaluated retrospectively. Anti-HIV seroprevalence was also evaluated with patient and tumor characteristics besides treatment regimens.
Fifty-one patients were included between September 1998 and February 2009. Male/female ratio was 3.25 (39/12). Median age was 68 (31-94). Lower extremity was the most common site whereas excisional biopsy was the most common diagnostic procedure. Smoking rate was 42.8%. Twenty percent had family history for cancer. Anti- HIV seropositivity rate was 1.9%. Thirty eight percent had local monotherapy, and radiotherapy was most common (26%). Multidisciplinary approach rate was 44%. Most of them had surgery and radiotherapy combination. Two-third of the patients had radiotherapy alone or with other modalities. Rates were as 12% for chemotherapy and 6% for interferon. Vincristine-bleomycin-doxorubicin combination was the most preferred regimen (60%).
Male patients in the sixth decade seem to have higher risk for KS. Smoking rate was almost as high. Local therapy might be sufficient in most of the patients. However, we may also consider systemic chemotherapy for selected patients, including vincristine, bleomycin and doxorubicin.
Clinical and Translational Oncology 09/2010; 12(9):629-33. · 1.33 Impact Factor
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ABSTRACT: In aggressive non-Hodgkin lymphoma (NHL), CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) regimen has been standard for decades, and rituximab has increased response rates and survival in CD20 positive patients, recently. The aim of this prospective trial was to evaluate the long-term efficacy and toxicity of MINE as a consolidation treatment in aggressive NHL patients who had achieved CR or unproven CR after six cycles of CHOP in the first line setting. The primary end-point was disease-free-survival (DFS). Thirty-eight patients were enrolled between February 1992 and May 2000. All of the patients received two cycles of MINE (mesna 1.3 g/m(2), ifosfamide 1.3 g/m(2), etoposide 65 mg/m(2) on days 1-3, and mitoxantrone 12 mg/m(2) on day 1, every 3 weeks) following response to CHOP. Initial bulky disease sites were also applied radiotherapy. Male/female ratio was 1.53(23/15). Median age was 49(30-73). Most of the patients had advanced stage (84.2% for stage >3) and high IPI score (79% for IPI score >2). Sixty percent had diffuse large cell histology. Median follow-up time was 118 months (9-195). Actual mean dose intensity was 88%. There were seven febrile neutropenia episodes. Two patients had grade two neuropathy, one had grade three mucositis and another one had non-neutropenic pneumonia. There was no early toxic death. No serious late toxicity was observed during long-term follow-up. Five- and 10-year DFS rates were both 65.3%. DFS rate in the patients with more than two poor prognostic factors according to IPI score is remarkably high (88%). Five- and 10-year OS was 62.5 and 59%, respectively. MINE regimen seems to be effective as a consolidation regimen, especially, in intermediate/high risk patients and has low early and late toxicities, and it warrants to be evaluated in phase III randomised trials with rituximab in CD20 positive aggressive NHL patients.
Medical Oncology 09/2009; 27(3):942-5. · 2.14 Impact Factor
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ABSTRACT: Telomerase is a specialized cellular reverse transcriptase that adds telomeric repeats (TTAGGG) at the ends of each chromosome. Nearly the complete spectrum of human cancers has been shown to be telomerase positive. The understanding of the telomerase regulation in concert with other genetic alterations in the process of malignant transformation of human cells has important clinical and practical implications. Regulation of telomerase activity (TA) is highly complex, and both putative positive and negative regulators have been reported. However, the mechanisms involved in telomerase regulation are not fully established. Identification of additional telomerase components and associated proteins will certainly contribute to further investigations of the effect of telomerase in telomere elongation, telomere length maintenance, oncogenesis, and functionally new, unidentified cellular functions. In this study our aim was to determine the chromosomal localizations of putative unidentified telomerase activator(s) and/or repressor(s) by high resolution-comparative genomic hybridization (HR-CGH) in highly telomerase expressing gastric tumor samples. For this purpose TAs and genomic imbalances were identified in the same tumor samples and relation between these was evaluated. Genomic changes affecting telomerase activity in 50 gastric tumor samples were investigated by HR-CGH. We have found that genomic imbalances including 1q+, 8p+, 8q+, 10q+, 17p-, and 20p+ are associated with the higher telomerase activity. Our results suggest that 1q24, 8p21-p11.2, 8q21.1-q23, 10q21-qter and 20pter-p11.2 may contain putative telomerase activator(s), whereas the 17p12 region may harbor candidate telomerase suppressor(s).
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 02/2009; 17(10):455-62. · 1.30 Impact Factor
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ABSTRACT: To depict the well-known and atypical magnetic resonance imaging (MRI) findings of non-neoplastic central nervous system (CNS) complications of extra- CNS tumors and portray additional information from advanced techniques, such as diffusion and perfusion MRI.
MRI scans of 92 patients were retrospectively evaluated based on the non-neoplastic effects induced by treatment or the remote effects of the tumor itself. Patients with brain metastases and/or patients who had whole brain radiation therapy were excluded so as not to take the primary radiation effects into consideration.
Sixteen patients (9 females and 7 males; age range, 11-68 years; median age, 45 years) had positive findings other than brain metastases. Six patients had posterior reversible encephalopathies, 3 patients had chemotherapy toxicity to the white matter, and 2 patients had acute strokes involving the posterior fossa and bilateral anterior circulation territory. Three patients had bilateral radionecrosis of the temporal lobe due to radiotherapy given for the vicinal tumor (nasopharyngeal carcinoma). One patient had encephalitis in the bitemporal region and one patient had cerebellar degeneration, each of whom had a paraneoplastic syndrome.
One of the major and noteworthy complications of malignancies directly affecting survival is brain metastasis, but non-neoplastic complications are infrequently encountered and are thus underestimated, either due to the absence of a true diagnosis or the lack of information pertaining to the clinical outcome. It is important for the radiologist to recognize these effects so as to help the clinician develop an optimal treatment strategy and avoid irreversible complications.
Diagnostic and interventional radiology (Ankara, Turkey) 07/2008; 14(2):61-8. · 1.10 Impact Factor
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ABSTRACT: In this non-randomized study we aimed to assess the efficacy of the addition of low molecular weight heparin (LMWH) to gemcitabine (GEM) plus cisplatinum (CDDP) combination chemotherapy on survival by prevention of thromboembolic complications in patients with advanced pancreatic cancer (APC).
Between November 1999 and February 2004, 69 consecutive patients with APC were treated with GEM (800 mg/m2, day 1, day 8) plus CDDP (35 mg/m2, day 1, day 8) every 21 days +/-LMWH (nadroparine calcium, 2,850 IU/day until disease progression). Ten out of 35 patients in LMWH group and 10 out of 34 patients in chemotherapy alone group had primary inoperable locally advanced disease and the rest of the patients had metastatic disease.
Total response rate was 58.8% (11.7% CR) for the patients treated with LMWH and 12.1% for those treated without LMWH (P = 0.0001). LMWH group had a better median time to progression (TTP) and survival when compared to control group (7.3 vs. 4.0 months, P = 0.0001; 13.0 vs. 5.5 months, P = 0.0001). The toxicity was similar and acceptable in both groups.
Addition of LMWH to GEM plus CDDP combination significantly improved the response and survival in patients with APC and the current schedule deserves to be tested in phase III trials.
Journal of Surgical Oncology 06/2007; 95(6):507-12. · 2.10 Impact Factor
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Southern Medical Journal 03/2007; 100(3):334-5. · 0.83 Impact Factor
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Güngör Utkan,
Abdullah Büyükçelik,
Bülent Yalçin,
Hakan Akbulut, Ahmet Demirkazik,
Dilek Dinçol,
Handan Onur,
Deniz Gören,
Umut Mousa,
Filiz Cay Senler,
Fikri Içli
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ABSTRACT: Malignant mesothelioma is a rare but notoriously chemoresistant tumor. An impressive activity of gemcitabine and cisplatin combination in malignant mesothelioma has been shown. However, the hematological toxicity and nephrotoxicity related to this regimen affect the patient's life negatively. The aim of this study is to investigate the efficacy and toxicity of divided dose of cisplatin combined with gemcitabine in chemo-naïve patients with malignant mesothelioma. Twenty-six eligible patients with malignant mesothelioma were enrolled onto the study. Cisplatin 35 mg/m(2) and gemcitabine 800 mg/m(2) were administered on days 1 and 8 as intravenous infusion in a 3-week cycle, up to maximum 6 cycles. Response and toxicity evaluations were performed in 26 patients. Male-female ratio was 11/15 with a mean age of 50.5 years (37-70). Locations of tumor were pleura in 16 patients, and peritoneum in 10 patients. All patients had epitheloid subtype of malignant mesothelioma. The partial response and stable disease were observed in 6 patients (23.1%) and in 13 patients (50%), respectively, with an overall tumor control rate of 73.1%. Seven patients (26.9%) had progressive disease. Median time to disease progression and survival were 4 and 19.5 months, respectively. Grade 3 nausea and vomiting were observed in one patient (3.8%), grade 4 neutropenia developed in one patient (3.8%) and grades 3-4 thrombocytopenia and nephrotoxicity did not develop. There was no treatment related death. Divided dose of cisplatin combined with gemcitabine, at the current dosage and schedule, appears to be an active regimen in chemotherapy-naïve patients with malignant mesothelioma, and well-tolerated.
Lung Cancer 10/2006; 53(3):367-74. · 3.43 Impact Factor
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ABSTRACT: Venous thromboembolism (VTE) is a well-recognized problem in malignancy. Patients with cancer who have VTE have a worse prognosis than other patients with cancer. Hypercoagulability in patients with cancer is related to malignancy itself and its treatment. These patients have multiple risk factors for thromboembolism, such as being immobilized, having central venous catheters, and receiving chemoradiation therapy. Cancer procoagulant, tissue factor, factor VIII, and thrombin have important roles in causing cancer-associated thromboembolism. Tumors require neovascularization for delivering oxygen and other nutrients. Therefore, angiogenesis facilitates tumor growth, invasion, and metastasis. New blood vessels formed by angiogenesis are thrombogenic. Hypercoagulability and tumor growth are closely related. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that may also cause VTE in patients with cancer. The relationship between cancer, angiogenesis, VEGF, and thrombosis is reviewed herein. Studies are ongoing to enhance our understanding of this complex interaction.
Supportive Cancer Therapy 10/2005; 3(1):28-34.
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Lung Cancer 01/2005; 46(3):377-8. · 3.43 Impact Factor
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ABSTRACT: Ifosfamide and doxorubicin are the most effective agents in the treatment of sarcomas, although their contributions to survival are usually limited. High-dose ifosfamide can be used as a salvage treatment in patients with recurrent or advanced sarcoma. We evaluated efficacy and toxicity of high-dose ifosfamide in the patients with recurrent or advanced sarcoma in this study.
39 patients with recurrent or advanced sarcoma were enrolled onto the study between 1996 and 2002. All patients had histological proven high grade sarcoma with measurable or evaluable disease. Ifosfamide was administered at the dose of 2 g/m(2) as continuous intravenous infusion for 24 h on day 1-9, in conjunction with the continuous infusion of mesna. Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor was given every cycle. The efficacy and toxicity of high dose ifosfamide (HDI) were evaluated clinically before subsequent cycle. The objective response was evaluated every two cycles. Histopathologic response was also evaluated in patients who underwent surgical resection.
Male/female ratio was 24/15, with a median age of 20 (11-48) years. 9 patients had locally inoperable advanced disease and 30 patients had metastatic disease. 10 patients were chemo-naive. The total number of HDI-chemotherapy cycles was 103 (median 2 cycles (range, 1 to 7)). 2 patients refused the further treatment after the first cycle and 1 patient died due to neutropenic sepsis in the first cycle of treatment. 36 patients were available for the evaluation of treatment efficacy. Overall response rates were 53.8% and 90% in pre-treated patients and in chemo-naive patients, respectively. Median follow-up time was 43 months. 13 patients underwent total surgical tumor resection. Pathologic complete response was observed in 5 of 13 these patients who underwent surgery. Median progression-free survival (PFS) was 7 months (95%CI: 3.8-10.2). The median progression-free survival (PFS) were 3 and 12 months in patients who did not have tumor resection, and in those having complete tumor resection (p = 0.002). Median overall survival (OS) was 10 months (95%CI: 0.0-20) in all patients. Median OS times were 8 months in patients without tumor resection and 26.5 months in patients with those underwent surgical treatment (p = 0.0369). 2 patients who underwent surgery are still alive and disease-free. Major toxicity was myelosuppression.
HDI seems to be feasible and effective in selected patients with advanced or recurrent sarcomas. Survival advantage of HDI is better when the total tumor resection can be done.
Experimental oncology 01/2005; 26(4):320-5.
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ABSTRACT: Irinotecan is an active drug after fluorouracil (FU) failure in patients with colorectal cancer (CRC). Also a modest activity of cisplatin and dacarbazine combination in FU resistant patients have been reported. We aimed to assess the efficacy of irinotecan, cisplatin and dacarbazine combination in previously treated patients with measurable advanced CRC.
Treatment schedule was irinotecan 150 mg/m2, iv, d1; cisplatin 20 mg/m2 and dacarbazine 200 mg/m2 iv, d1-d3; every 21 days. 48 patients with a median age of 51 were entered the study.
Objective response rate was 33.3%. The overall disease stabilization rate was 75.6%. The median survival was 14 months, and the median progression-free survival was 7 months. Main toxicities were grade 2-3 vomiting (39.2%) and grade 3-4 neutropenia (17.4%).
CPD combination seems to be very active, with acceptable safety profile, in patients with advanced CRC resistant to FUFA.
Experimental oncology 07/2004; 26(2):149-52.
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ABSTRACT: This study was designed to examine the relationship of prior therapy, bone marrow metastases, mobilization, and blood progenitor/stem cell (BSC) collection in breast cancer patients. Cells were collected from 19 breast cancer patients during steady state (nonmobilized group) and from 69 breast cancer patients after cytokine administration (mobilized group). Characteristics of the patients were compared with the cells obtained. A significant inverse association was found between the number of chemotherapy regimens the patients had received prior to BSC collection and the mononuclear cell (MNC) count of the product per liter of blood processed (LBP) with apheresis (P = .0006) and the granulocyte monocyte/macrophage colony-forming cell (GM-CFC) numbers per LBP (P = .0002). This association was evident in both mobilized and nonmobilized patients. Similar results were seen in those 25 patients who had received prior radiation therapy (MNC/LBP, P = .0003; GM-CFC/LBP, P = .0004). Patients in both the mobilized and nonmobilized groups with marrow metastases at the time of collection also had significantly lower levels of MNC/LBP (P = .0039) and GM-CFC/LBP (P = .0001) than did those without marrow metastases. The findings suggest that prior administration of radiation therapy and/or chemotherapy and the presence of marrow metastases all negatively impacted the collection of mobilized and nonmobilized progenitor cells from breast cancer patients. The mechanisms of this impact are not understood.
Biology of Blood and Marrow Transplantation 02/2002; 8(5):268-72. · 3.87 Impact Factor
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Annals of Saudi medicine 24(6):473-5. · 1.07 Impact Factor
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ABSTRACT: Sarcomas are heterogeneous groups of tumors that are seen rarely. Although great efforts have been made to identify prognostic factors apart from grade, histology and tumor size, they're not so obvious yet. In this study, the prognos-tic role of serum matrix metalloproteinase (MMP)-9 levels in patients with sarcoma was evaluated. Eighty-eight patients with a diagnosis of sarcoma were included in the study. Additionally in 14 patients with osteosar-coma, serum MMP-9 levels were analyzed twice, one in preoperative period during neoadjuvant chemotherapy and one in postoperative period. Sixteen healthy volunteers composed the control group. Serum MMP-9 levels have been evaluated quantitively by ELISA method. Serum MMP-9 levels were higher significantly compared to control group (p<0.005). Patients with metastatic disease have higher serum MMP-9 levels compared to the non-metastatic ones which were statistically non-significant (p: 0.9). Similarly, no difference in serum MMP-9 levels was observed between patients with intermediate-high grade tumors and with low grade tumors. Moreover, statistically significant decrease in serum MMP-9 levels was observed in patients in postoperative period compared to preoperative period (p: 0.016). Although this study was performed in small number and heterogeneous group of patients, the difference in serum MMP-9 levels between sarcoma patients and control group, especially in the presence of measurable lesions and in postoperative period of the same patients, suggests that serum MMP-9 levels may be used as a tumor marker in patients with sarcoma. ÖZET Sarkomlu Hastalarda Serum Matriks Metalloproteinaz-9 Düzeyinin Prognostik Değeri Sarkomlar oldukça nadir olarak gözlenen heterojen bir tümör grubudur. Tüm çabalara karşın tümör histolojisi, greydi ve tumor boyutu dışında bir prognostik faktör tayin edilememiştir. Bu çalışmada sarkomlu hastalarda serum matriks metalloproteinaz-9 (MMP-9) düzeyinin prognostik değeri araştırıldı.
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ABSTRACT: Neurologic paraneoplastic syndromes are rare in patients with ovarian cancer. These syndromes may point out an occult or relapsed disease. The management of the majority of neurologic paraneoplastic syndromes is difficult because no standard treatment is available but some type of them may subside with the treatment of underlying can-cer. We present a case of neurologic paraneoplastic syndrome as a first symptom of relapsed ovarian cancer. Howev-er, we could not specify the syndrome with its clinical features and electrophysiological study. It subsided greatly fol-lowing the cytotoxic chemotherapy for ovarian cancer and re-occured with the appearance of resistance to chemother-apy. ÖZET Non-Spesifik Nörolojik Paraneoplastik Sendromla Ortaya Ç›kan Okkült Over Kanser Nüksü: Olgu Sunumu Over kanserli hastalarda nörolojik paraneoplastik sendromlar seyrektir. Bu sendromlar, gizli veya nüks etmiş hastal›ğa işaret edebilir. Nörolojik paraneoplastik sendromlar›n standart bir tedavi seçeneği olmad›ğ› için tedavileri zordur. Ancak baz› tipleri, altta yatan kanserin tedavisiyle düzelebilir. Bu raporda, nüks etmiş over kanserinin ilk semptomu olarak beliren nörolojik paraneoplastik sendromlu bir olguyu sunmaktay›z. Olgunun klinik özellikleri ve elektrofizy-olojik çal›şma ile sendromu tam olarak spesifiye edemedik. Over kanseri için uygulanan kemoterapi ile belirgin olarak düzeldi ve kemoterapi direncinin ortaya ç›kmas›yla yeniden oluştu.
