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Biomedical subjects

A Aydiner

Publications and source records attributed to A Aydiner.

At least 19 recordsLinked to original sources

Combination chemotherapy with docetaxel and irinotecan in metastatic malignant melanoma.

AIM: The aim of the current trial was to assess the efficacy and toxicity of 3-weekly intravenous docetaxel and irinotecan in the treatment of patients with metastatic malignant melanoma. MATERIALS AND METHODS: Sixteen patients with no history of previous cytotoxic agents or immunological treatment for advanced disease were treated with docetaxel 50 mg/m2 and irinotecan 150 mg/m2 intravenously over 60 min every 21 days. Prior immunotherapy with interferon and chemotherapy for adjuvant therapies were accepted provided there was a minimum 4-week treatment-free interval. Response evaluation was performed after two cycles. RESULTS: None of the patients had chemotherapy-induced tumour response. Eight patients achieved stable disease and others had progression of disease. The median survival time was 136 days (95% CI: 30.2-241.8), and the 3-month survival rate was 62.5%. Patients with stable disease (n = 8) had a longer survival than non-responders (P = 0.023, Breslow test). Generally side effects were mild and tolerable. Grade III-IV haematological toxicity occurred in approximately 10%. Severe emesis, stomatitis and diarrhoea was seen in less than 20% of the patients. Alopecia was observed in all patients. CONCLUSION: A 3-weekly intravenous docetaxel and irinotecan combination appears to be inactive in the treatment of patients with malignant melanoma and has not been recommended.

Adult↗

Efficacy of cisplatin and cyclophosphamide combination for recurrent and metastatic carcinoma of the uterine cervix.

The efficacy of a combination of cyclophosphamide and cisplatin in patients with metastatic and recurrent carcinoma of the cervix, was tested. Thirty patients were included in the study. Initially, 27 patients (90%) had received pelvic radiation and intracavitary boost and one patient was additionally given paraaortic radiation. Cisplatin was given at 75 mg/m2 followed by cyclophosphamide at 750 mg/m2 on day 1 with three weekly intervals for a maximum of six cycles. All patients received a median of four cycles of chemotherapy. The overall response rate for all eligible patients was 20% (continuous CR: 1, CR: 1, PR: 4 patients). Overall response rate and progressive response in patients with relapse within the previous radiation field were 9.5% and 66.7%, respectively; while for patients who had recurrent disease outside any irradiated area both were 44.4%. Eighteen patients (60%) had early withdrawal from the planned schedule, which was due to patient incompliance in seven patients (23.3%), disease progression in ten (33.3%) and early death after the first cycle in one patient (3.3%). Anemia was the most frequent toxicity, necessiating 24 transfusions in nine patients (30%). WHO grade 3 and 4 toxicity were anemia: 13 (43.3%), leucopenia: one (3.3%), thrombocytopenia: two (6.6%), renal: one, emesis: nine (30.0%) patients. The median survival duration for all eligible patients was 11 months. Univariate analysis revealed that progressive response to chemotherapy was the only prognostic factor for survival (7.1 vs 16.8 months, p = 0.003). The combination of cisplatin and cyclophosphamide did not appear to be more active than single agent cisplatin in this patient group with a relatively poor prognosis. Further studies are required to determine a better therapeutic approach for patients with relapsed carcinoma of the cervix.

Adenocarcinoma↗

Acetaminophen modulations of chemotherapy efficacy in MDAH 2774 human endometrioid ovarian cancer cells in vitro.

Epidemiological data have correlated consumption of nonsteroidal antinflammatory drugs with lowered risk for many types of cancer, and some recent studies indicate a reverse correlation with acetaminophen consumption and ovarian malignancy. In this study we examined effects of acetaminophen on plating, S-phase and colony growth of MDAH 2774 human endometrioid ovarian carcinoma, as well as sensitivity of this cell line to carboplatin in all three tests, and paclitaxel to clonogenic assay. Acetaminophen significantly enhanced S-phase in first 72 hours and enhanced cell population in 96 hours of plating monitorization, but decreased one week colony growth by approximately 80%, which was in the range of cytotoxic drugs. Interestingly with low dose carboplatin in first 72 hours acetaminophen enhanced cell proliferation more profoundly, but only thereafter decreased cell growth synergistically with carboplatin. It did not effect paclitaxel colony growth inhibiting acitivity. MDAH-2774 cell line lack p-53 and MSH-2, which are both 'gatekeeper' apoptosis inducing genes against genome damaging insult. Thus, presence of lower doses of oxidizing drugs may help the induction of proliferative signals, but only their sustained presence may overcome such signals and ultimately bring to cell demise.

Acetaminophen↗

Vascularization pattern of C6 glioma is modified with medroxyprogesterone acetate and ibuprofen in Wistar rat brain.

Beneficial effects of medroxyprogesterone acetate (MPA) in cancer therapy is partly mediated via its antiangiogenic activity. The same is true for the antitumoral action of non-steroidal antiinflammatory drugs. We have studied two liposoluble drugs, MPA and the analgesic ibuprofen, on glioma vascularization in vivo. In this study we have shown that, until the sacrifice at 27. day after tumor inoculation in the right hemisphere, MPA had a slight though insignificant activity to reduce the fatality of C6 glioma, growing in right cerebral hemisphere of male Wistar rats. But ibuprofen both alone or with MPA had no effect on survival with gavage application of a 30 mg/kg/day dosing regime. On histological analysis, intra- and peritumoral vessels were counted. Progesterone seemed to lower intratumoral, but to increase peritumoral vessels, especially glomeruloids, around the tumor mass. Coadministration of ibuprofen acted to suppress the peritumoral vessel increase, and to enhance lymphomonocytic infiltration around tumor vessels.

Animals↗

Thymidine labeling index in epithelial ovarian cancer.

OBJECTIVE: The aim of this study is to determine the thymidine labeling index and its prognostic role in patients with ovarian cancer. METHODS: Tumor cell proliferation in 32 patients with primary ovarian cancer admitted to Istanbul Medical Faculty, Department of Obstetrics and Gynecology, between 1993 and 1997 was investigated using the [3H]thymidine labeling index (TLI). TLI results were compared with other clinical and histopathologic prognostic parameters. RESULTS: The mean and median TLI values of the patients were 9.3+/-6.2% and 9.20% (range: 0.4-23.0%), respectively. Sixteen patients showed high proliferation rates (mean TLI: 14.3%). These patients had an overall survival rate of 46.7% at 3 years. The mean TLI level and overall survival at 3 years in the low proliferation rate group were 4.4 and 68.8%, respectively. Patients with a high TLI had a significantly shorter survival compared to those with a low TLI (P<0.01). There was tendency towards a higher TLI with advanced stage (P>0.05). However, there was no statistically significant correlation between TLI and other prognostic parameters. CONCLUSION: TLI may have a predictive value in determining the outcome of patients with ovarian cancer. Further larger scale studies are needed before definite conclusions can be made about its role as a prognostic factor in this disease.

Adult↗

Biological considerations in locally advanced breast cancer treated with anthracycline-based neoadjuvant chemotherapy: thymidine labelling index is an independent indicator of clinical outcome.

The present retrospective study aims to determine the clinical value of thymidine labelling index (TLI) together with other established clinical and biological factors in 116 locally advanced breast cancer (LABC) patients treated with anthracycline-based neoadjuvant chemotherapy, surgery, adjuvant chemotherapy and radiotherapy. TLI was determined in 71 LABC patients with a median of 2.62% (0-23.64%) and a mean of 4.71% +/- 5.54. As a result of neoadjuvant chemotherapy, 85 patients (73%) responded to chemotherapy (CT), whereas 31 patients were unresponsive (27%). No relationship has been found between the pretreatment biological variables including TLI, estrogen receptor (ER), progesteron receptor (PgR) status and clinical parameters such as the chemotherapy response rates and axillary lymph node involvement following chemotherapy. Median follow-up was 35 months (18-97 months) and the 3-year overall survival (OS) and disease free survival (DFS) rates were 71.6% and 52.2%, respectively. In univariate analysis, patients with inflammatory breast cancer, high TLI-index (> or = 2.62%), lymph node (LN) positivity or > 3 positive lymph nodes following neoadjuvant chemotherapy and without any response to neoadjuvant chemotherapy were found to have worse DFS and OS-rates and high local and systemic recurrence rates. In multivariate analysis, TLI was estimated as the most powerful independent factor affecting the OS in LABC patients among the other established clinical and biological parameters (p = 0.02). These results suggest that TLI is an important independent indicator of clinical outcome in patients with LABC and these patients with high TLI levels require more effective treatment modalities.

Adult↗

Measurement of serum CA 19-9 may be more valuable than CEA in prediction of recurrence in patients with gastric cancer.

In 35 patients with recurrent gastric cancer who had undergone curative gastrectomy, serum carcinoembryonic antigen (CEA) and CA 19-9 (carbohydrate antigen) tumor marker levels were investigated. At least one tumor marker was elevated in 24 (68.6%) patients. The levels of serum CA 19-9 and CEA markers were increased in 20 (57.1%) and 12 (34.3%) patients, respectively. This difference was not statistically significant. However, it may be important in terms of clinical practice.

CA-19-9 Antigen↗

Stevens-Johnson syndrome in a patient receiving anticonvulsant therapy during cranial irradiation.

A 28-year-old female patient with a recent history of breast carcinoma was referred to our clinic with generalized necrotic skin eruptions and severe mucosal erosions, which developed right after the completion of cranial radiotherapy for brain metastases. She had been receiving prophylactic diphenylhydantoin treatment 100 mg three times daily during radiation therapy. The extensive involvement of the oral mucosa with conjunctivitis and synechiae of the eyelids, facial swelling, and extension of the rash over the trunk and shoulders with bullous detachment of less than 10% of the total body surface strongly suggested Stevens-Johnson syndrome caused by phenytoin treatment in our patient. There has been conflicting evidence on the role of radiotherapy in the increased risk of severe drug reactions. Although various authors have emphasized the augmented rate of severe mucocutaneous reactions caused by anticonvulsants given during radiotherapy and suggested discontinuing the prophylactic use of such drugs in patients with no history of seizures, others have argued in favor of prophylactic anticonvulsants. Given the high risk of seizures, reaching 20% in patients with brain tumors, and the low incidence of drug reactions, the suggestion of refraining from prophylactic anticonvulsants in the setting of primary or metastatic brain tumors is controversial.

Adult↗

Serum lactate dehydrogenase levels at presentation predict outcome of patients with limited-stage small-cell lung cancer.

Serum lactate dehydrogenase (LDH) is a biochemical parameter that is elevated in the majority of extensive-stage small-cell lung cancer (SCLC). In this study, distribution and prognostic importance of serum LDH in limited-disease SCLC were investigated. Serum concentrations of LDH were measured in 184 patients at initial examination. These results were compared with prospectively recorded clinicopathologic characteristics and patient outcome data. Significant positive association was found between LDH levels and weight loss, performance status, response to chemotherapy, and albumin but not between age, gender, and hemoglobin values. Patients with high concentrations of LDH had a significantly worse prognosis than did patients with normal levels. The probability of overall survival at 1 year was 60.2% in patients with normal serum LDH levels and 33.1% in patients with higher values (p = 0.0017). Also, the prognostic value of LDH on overall survival was shown in multivariate analysis (p = 0.05). At the time of diagnosis, serum levels of LDH appear to have a significant relation to outcome in patients with limited-stage SCLC.

Adult↗

Prognostic factors in pancreatic carcinoma: serum LDH levels predict survival in metastatic disease.

In this study, our aim was to investigate the impact of various prognostic factors on survival in patients with pancreatic carcinoma. The group consisted of 127 cases with adenocarcinoma histologically. The patients had a median age of 58 years, and 81 (64%) were male. The median survival time of the whole group was 7 months, and the 4-year survival rate was 18%. The median survival duration of the patients without metastases was 8 months, and the survival rate at 1 year was 37.5% and 7.2% at 5 years. It was associated with improved survival compared with the cases with metastatic disease (p < 0.0001). In univariate analysis, decreased performance status (p = 0.0009) and unresectability of tumor (p < 0.0001) were associated with poor outcome. However, only surgery was found to be a statistically significant parameter in multivariate analysis (p = 0.002). The median survival duration of patients with metastases was 5 months, and the 1-year survival rate was 10%. Age younger than 60 years (p = 0.04), decreased serum hemoglobin levels (p = 0.04), and elevated lactic dehydrogenase (LDH) levels (p = 0.0001) were associated with a significantly shorter survival rate. In the Cox model, a high serum LDH level was the only independent unfavorable prognostic factor (p = 0.001). In conclusion, surgical intervention in the group without metastases and serum LDH levels in the group with metastases were the most important prognostic factors influencing survival. Pretreatment serum LDH determinations may provide a useful means of stratifying patient populations when comparing treatment programs for advanced pancreatic cancer.

Adenocarcinoma↗

Autophagy and nuclear changes in FM3A breast tumor cells after epirubicin, medroxyprogesterone and tamoxifen treatment in vitro.

OBJECTIVE: Autophagy is a form of physiological programmed cell death which is observable after hormonal withdrawal. In this study, the FM3A murine breast tumor cell line was treated with epirubicin alone and with medroxyprogesterone acetate (MPA) or tamoxifen, to determine if structural and kinetic signs of autophagy may also occur in an enhanced manner during epirubicin sensitization via hormonal agents. METHODS: One-week soft agar colony growth, 96-hour values of plating and pulse thymidine labeling and electron microscopical examinations were performed following treatment with MPA and tamoxifen alone or with epirubicin. RESULTS: Tamoxifen induced signs of autophagy, which was enhanced when it was combined with MPA. Epirubicin also induced autophagy of secretory granules, which coalesced to form an intracytoplasmic lumen. Combining MPA with epirubicin enhanced the formation of apoptotic blebs and chromatin fragmentation. When epirubicin was combined with tamoxifen, peculiar nuclear structures were formed. CONCLUSIONS: Hormonal agents may modulate anthracycline activity towards specific patterns in eliciting cell death, via autophagy and/or as yet unknown nucleolus-specific interactions.

Antibiotics, Antineoplastic↗

The efficacy of combination chemotherapy including intraperitoneal cisplatinum and mitoxantrone with intravenous ifosfamide in patients with FIGO stage I C ovarian carcinoma.

OBJECTIVE: Patients with stage I ovarian cancer show a high incidence of recurrent disease ranging from 30% to 50%, which may be associated with a shortened survival. Therefore, a subset of early-stage patients with poor prognostic factors who are most likely to present with recurrent disease in the next few years may benefit from adjuvant treatment. PATIENTS AND METHOD: In this pilot study, we evaluated the efficacy of combination chemotherapy including intraperitoneal mitoxantrone (12 mg/ml) and cisplatinum (75 mg/ml) on day 1, in addition to intravenous ifosfamide (4000 mg/m2) given on day 15 with mesna protection. Thirteen patients with a median age of 44 years were included in the study. RESULTS: Following a median of 5 cycles of chemotherapy, 12 patients had a complete response (92.3%), while one patient had progressive disease. At the latest follow-up, ten patients were alive with no evidence of disease, two patients had died and one patient was lost to follow-up. Overall and progression-free survival rates at eight years were 82.5+/-11.3% and 83.9+/-10.5%, respectively. Excluding grade 3 and 4 abdominal pain in three (23.1%) patients, there were no serious complications associated with this combination. Dose delay not longer than one week was observed in 3 cycles (5.6%). Port-related complications observed in three patients were colonic perforation, hematoma and leakage. CONCLUSION: This combination has moderate efficacy and tolerable toxicity. However, further studies are required to make definite conclusions regarding the efficacy of this combination in the adjuvant setting in patients with high-risk early stage ovarian carcinoma.

Adenocarcinoma, Clear Cell↗

The role of chemotherapy in malignant mixed mullerian tumors of the female genital tract.

Thirteen patients with malignant mixed mullerian tumor of the female genital tract, treated and followed in our clinic from 1989 to 1999 were retrospectively evaluated. Seven patients (53.8%) with advanced disease or postoperative residual tumor were treated with adjuvant chemotherapy. The median age at diagnosis was 64 years (range: 26-79). All patients underwent primary surgical cytoreduction. Tumors were localized to the endometrium in five (62.5%), to the ovaries in two (25%) and to the fallopian tube in one (12.5%) patient. One patient with endometrial carcinosarcoma had a simultaneous second primary ovarian epithelial carcinoma. Two patients (25%) had a heterologous sarcomatous component. Myometrial involvement included less than half the thickness in one patient, while there was no myometrial invasion encountered in two patients. Five patients (38.5%) had more than 50% of the myometrium invaded. Two patients received additional radiotherapy. Six patients received cisplatinum-based chemotherapy (4 had doxorubicin including combinations), while one patient was treated with a doxorubicin+ifosphamide combination. Five patients (71.4%) had a complete response (CR) to chemotherapy. Response duration in patients with a CR was +13, +67, +10, +14 and +2 months, respectively. After a median follow-up period of 20 months (3-115 months), six patients have died, five are being followed-up with no evidence of disease, one is alive with metastatic disease and one patient is under treatment. Malignant mixed mullerian tumor of the female genital tract is highly responsive to multimodality treatment strategies. Further prospective studies are required to identify distinct prognostic groups that may benefit from various treatment modalities.

Adolescent↗

Celsite port and catheter as an intraperitoneal access device in the treatment of ovarian cancer.

BACKGROUND AND OBJECTIVES: In ovarian cancer, development of safe and effective methods for providing long-term access to the peritoneal cavity has become increasingly important. METHODS: A modified Port-A-Cath (Celsite-port and catheters, B. Braun, Chasseneuil, France) was used in 56 patients with presumed epithelial ovarian cancer at the conclusion of primary or second-look laparotomy. In 37 patients, ports were located on the right costal margin in the midclavicular region and in 19 in the xiphoid region. RESULTS: In 56 catheters, 8 (13.8%) complications of severe or moderate degree during the treatment were registered. In-flow obstruction of device occurred in 6 patients, and there was 1 viscous perforation and 1 catheter related infectious peritonitis. Grade III-IV pain and in-flow obstruction were developed in the patients with ports implanted on the right costal margin but not with ports implanted in the xiphoid region. CONCLUSION: The complication rate of intraperitoneal access devices is comparatively low.

Adult↗

The roles of chemotherapy and surgery in gastric carcinoma and the influence of prognostic factors on survival.

In this study, we present the results of surgery and chemotherapy and the impact of various prognostic factors on survival in patients with gastric carcinoma with a follow-up of 6 years. All of the 328 cases were adenocarcinoma histologically and had a median age of 55 years. Median survival was 11 months, and the 5-year survival rate was 18%. Nonmetastatic cases were associated with improved survival as compared with the cases with metastatic disease (p<0.001). Patients with gastrectomy had improved survival (p<0.001). Subtotal gastrectomized patients had better survival rates in comparison to the total gastrectomized patients (p = 0.03). Addition of splenectomy to total gastrectomy and adjuvant chemotherapy did not influence survival rates (p>0.05). In metastatic patients, we determined beneficial effects of gastrectomy and chemotherapy on survival. The benefit was most predominant in chemoresponsive patients (p<0.001). Higher serum CA 19.9 levels in patients without metastases, higher serum lactate dehydrogenase and carcinoembryonic antigen levels in patients with metastases, and lower serum albumin levels in both stages were determined as significant predictors of poor survival. On multivariate analysis, only higher serum CA 19.9 level was the independent unfavorable prognostic factor of survival time in nonmetastatic patients (p = 0.008). In metastatic disease, older age (p = 0.03) and male gender (p = 0.05) were associated with poorer survival. In conclusion, gastric cancer is a great health problem, especially in developing countries, and we need more optimal approaches and treatment modalities for gastric cancer.

Adenocarcinoma↗

Multiple primary neoplasms at a single institution: differences between synchronous and metachronous neoplasms.

During the 10-year period (1987-1996) of our study, 26,255 patients with cancer were admitted to our clinic and, of these, 271 (1%) patients had multiple primary malignant tumors. Ninety-two (34%) patients had synchronous tumors (synchronous group), and 179 (66%) patients had metachronous tumors (metachronous group). The mean age at first diagnosis was higher in the former group. The ratio of men to women was 1.36 in the synchronous group and 0.74 in the metachronous group (p = 0.018). Smokers and drinkers were more common in the synchronous group. Breast cancer and lung cancer were most prevalent, and associations between head/neck and lung cancer and between breast and breast cancer were the most frequent associations in both the synchronous and the metachronous group. The frequency of aerodigestive tumors was higher and that of mesenchymal tumors was lower in the synchronous group than in the metachronous group. Localization in the medial region and in the head/neck was more frequent in the synchronous group than in the case of metachronous secondary tumors.

Age Factors↗