Comparison of Weekly Low Dose Docetaxel with the Standard Protocol in Hormone-resistant Metastatic Prostate Cancer.

OBJECTIVE: To evaluate and compare the effects and toxicity of weekly low dose with three weekly standard doses of docetaxel in hormone-resistant metastatic prostate cancer. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: University of Health Sciences, Ankara Training and Research Hospital, Ankara, Turkey, from January 2013 to July 2021. METHODOLOGY: The study was conducted on 79 patients with refractory prostate cancer. Patients were assessed in 2 groups. One group was treated with the classical standard Docetaxel dose 75 mg/m2/day (every 3-week) + Prednisolone 10 mg/day (daily), whereas the second group consisting of elderly and poor performance status received a low dose Docetaxel 25 mg/m2/day (weekly, 1-week interval) + Prednisolone 10 mg/day (daily). RESULTS: The overall survival and toxicity profile differences between the low dose protocol in this study and the standard treatment protocol were compared. Survival times in both groups were found as 44.3 months and 35.5 months in 1-week and 3-week interval groups, respectively (p = 0.09). The rate of hematologic toxicity associated with systemic treatment was 10% in the 1-week interval treatment group and 41% in the 3-week group (p = 0.002). In particular, the febrile neutropenia was 30.8% in the 3-week interval group and 2.5% (p = 0.001) in the 1-week interval group. CONCLUSION: The study showed that instead of using docetaxel in the standard dose and range, it is more tolerated in elderly and poor performance patients when administered in the revised dose. The disrupting effects of chemotherapy are overperforming, especially in such patients. KEY WORDS: Metastatic prostate cancer, Hormone resistant prostate cancer, Weekly docetaxel.

Optimal timing of adjuvant treatment in patients with early breast cancer.

It is well established that adjuvant treatment reduces mortality after early breast cancer. However, the optimal timing of adjuvant treatment is not well described. To determine the optimal timing of adjuvant treatment, 402 breast cancer patients who received adjuvant treatment at Ankara Oncology Research and Training Hospital between January 1995 and August 2002 were evaluated retrospectively. Three hundred and fifty-seven (88.8%) patients received adjuvant chemotherapy, 204 (50.7%) of these patients received only adjuvant chemotherapy and 153 (38%) patients received tamoxifen following chemotherapy. Remaining 45 (11.2%) patients received only adjuvant tamoxifen. The median time to start adjuvant treatment after surgery was day 21 (range, days 4 to days 258), and the median follow-up was 50 months (range, 6-105 months). The patients were divided into 5 groups according to starting time of chemotherapy (shorter than 14 days, between days 15-29, between days 30-44, between days 45.-59 and more than 59 days). Overall survival (OS) and disease-free survival (DFS) were not shown significantly different between for 5 groups (P>0.05). Secondly, patients were divided into two groups as starting adjuvant treatment equal to or shorter than 44 days and longer than 44 days (n=344, 85.6% and vs. n=58, 14.4%, respectively). OS was significantly better in patients who started to receive adjuvant treatment within 44 days after surgery compared to patients who received adjuvant treatment after 44 days (92 vs. 83.3%, P=0.03) for 5 years, but DFS was not significantly different between two groups (83.4 vs. 82.2%, P>0.05). According to our study, adjuvant treatment of breast cancer should be initiated earlier after surgery.

Risk factors of nasopharyngeal carcinoma in Turkey-an epidemiological survey of the Anatolian Society of Medical Oncology.

BACKGROUND: Nasopharyngeal carcinoma is a rare disease in most parts of the world with a multifactorial etiology involving an interaction of genetic, viral, environmental and dietary risk factors. This is the first epidemiologic study aimed to evaluate the risk factors of nasopharyngeal carcinoma in the Turkish population. METHODS: We conducted a multicentric, retrospective, case-control study using a standardized questionnaire which captured age, sex, occupation, household type, blood group, dietary habits, smoking, alcohol consumption and oral hygiene. The study included 183 cases and 183 healthy controls matched by sex and age. Multiple logistic regression and univariate analysis were employed. RESULTS: The peak age incidence was 40-50 years and the male to female ratio was 2:1. We observed significant associations between elevated nasopharyngeal carcinoma risk and low socioeconomic status, rural household type (OR:3.95, p<0.001), farming (OR:4.24, p<0.001) and smoking (OR:3.15, p<0.001). Consumption of french fries (OR:1.44, p=0.024), fried meat (OR:1.05, p=0.023) and tea (OR:5.55, p<0.001) were associated with elevated risk, while fresh fruit consumption was associated with reduced risk (OR:0.59, p=0.011). An irregular meal pattern was also a risk factor (OR:1.75, p=0.012). There were no significant associations between consumption of grain, diary products, alcohol and nasopharyngeal carcinoma risk (p>0.05); furthermore salty foods had a borderline p value (OR:2.14, p=0.053). Blood type A increased the risk (OR:2.03, p=0.002) while blood type 0 was a protective factor (OR:0.53, p=0.009). Rare habit of teeth brushing (OR:6.17, p<0.001) and ≥ 10 decayed teeth before diagnosis (OR:2.17, p<0.001) increased the risk. CONCLUSIONS: The nasopharyngeal carcinoma risk factors described in the literature are also applicable for the Turkish population. People with type A blood are at risk in Turkey. Salted foods have also a border risk out of the endemic regions. This is the only study showing that poor oral hygiene is a serious risk factor for nasopharyngeal carcinoma.

Primary adult soft tissue sarcomas: analysis of 294 patients.

We retrospectively analyzed 294 patients with primary soft tissue sarcoma followed between 1996 and 2002 in Ankara Oncology Hospital. There were 170 male and 124 female patients with the age range of 16-80 years. The primary tumor was in the extremity in 72.9% of the patients. We determined lung metastasis in 102 (85%) out of the 120 patients as distant metastasis. The most common adult sarcomas were liposarcoma (16.3%), malignant mesenchymal tumor (MMT) (13.9%), malignant fibrous histiocytoma (MFH) (11.2%), rhabdomyosarcoma (10.2%) and synovial sarcoma (10.2%). Seventeen patients (5.3%) had grade 1 tumor, 143 patients (52.2%) had grade 2 tumor, and 112 patients (41.4%) had grade 3 tumor. In 45 patients (15.3%), the grade of the tumors is unknown. The tumor size was 0 to <5 cm in 54 cases (19.4%), 5-10 cm in 117 cases (41.9%) and >10 cm in 108 cases (38.7%). In 15 cases (5.1%), tumor size was unknown. Ninety-five patients (32.4%) were treated with adjuvant chemotherapy, and 125 patients (42.7%)) were treated with palliative chemotherapy. Prognostic factors influencing the overall survival were tumor size, grade, adjuvant radiotherapy and chemotherapy. Adjuvant radiotherapy had influence on disease-free survival. While tumor grade and size showed a significant value for predicting local recurrence, grade, localization of tumor, adjuvant chemotherapy and radiotherapy had an impact on metastasis development. The 1-year overall survival for all patients was 73.4%, 3-year overall survival was 51.8%, and 5-year overall survival was 45.1%.

UFT plus oral folinic acid with alternating oral and intravenous vinorelbine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes.

BACKGROUND: We retrospectively evaluated the activity and toxicity of uracil/tegafur (UFT) plus oral folinic acid in combination with vinorelbine (alternating intravenous (IV) on day 1 and oral on day 8) in patients with metastatic breast cancer. PATIENTS AND METHODS: Treatment consisted of IV vinorelbine 25 mg/m(2) on day 1 and 60 mg/m(2) orally on day 8, and oral UFT 300 mg/m(2) plus leucovorin 60 mg/m(2) on days 1-14 with 21 days interval. All patients were refractory to anthracyclines and taxanes. RESULTS: Partial response (PR) was observed in 3 (9.7%) and stable disease (SD) was observed in 13 (41.9%) patients. Total clinical benefit (PR + SD) of the combination was 51.6%. The median response duration was 3 (range 1-11.8) months. Median overall survival was 9.8 months (95% confidence interval (CI): 7.5-12.1), and median time to progression was 3.4 months (95% CI: 2.3-4.5). The most common toxicities were hematologic, including 4 (12.9%) cases of grade 3 neutropenia and 4 (12.9%) cases of grade 4 neutropenia. Grade 3 diarrhea was reported in 2 (3.2%) patients. 3 (9.7%) patients had hand-foot syndrome. Febrile neutropenia was observed in 1 patient. CONCLUSIONS: Although the combination is safe and convenient in clinical practice, it has only moderate activity in metastatic breast cancer patients.

Gemcitabine combined with uracil-tegafur in patients with advanced pancreatic cancer.

The aim of the study was to evaluate the efficacy and tolerability of gemcitabine and uracil-tegafur (UFT) combination in patients with advanced pancreatic carcinoma, retrospectively. Thirty-one patients, including 27 with metastatic disease, were treated with gemcitabine at a dose of 1000 mg/m2 in 30 minutes on days 1 and 8, and oral UFT 300 mg/m2 on days 1-14, as the first-line regimen in advanced stage. The cycle was repeated every 21 days. A total of 116 cycles of chemotherapy were administered, with a median of 3 cycles per patient (range 1-13). The objective response rate was observed in 6 (19.3%) patients with 1 (3.2%) complete response, and 5 (16.1%) partial responses. The median response duration was 4 (range, 3-14) months. Eight (25.8%) patients had a standard deviation of more than 3 months. Median overall survival was 8 months (95% CI, 6-10 months) and median time to progression was 4.2 months (95% CI, 1-6 months). This combination was generally well tolerated. There were no life-threatening side effects. Most common toxicities were of hematologic and gastrointestinal nature. In conclusion, this regimen was well tolerated and seemed to have a moderate activity in the palliative treatment of advanced pancreatic carcinoma.

Efficacy and toxicity of gemcitabine and pegylated liposomal Doxorubicin in recurrent platinum-resistant/refractory epithelial ovarian cancer.

BACKGROUND: Treatment of patients with platinum resistant/refractory ovarian cancer is a significant problem. In this study, we evaluated the efficacy and tolerability of the combination of gemcitabine and pegylated liposomal doxorubicin (PLD) in patients with platinum resistant/refractory ovarian cancer. PATIENTS AND METHODS: We retrospectively evaluated the activity and toxicity of gemcitabine and PLD combination in 35 patients with recurrent platinum resistant/refractory ovarian cancer who had been treated and followed up in 7 centers in Turkey between December 2005 and June 2008. The patients received gemcitabine 1.000 mg/m(2) on day 1 and 8, and PLD 25 mg/m(2) on day 1 every 28 days. RESULTS: A total of 187 cycles (median, 6 cycles) were delivered. An objective response rate of 28,6 % (1 complete, 9 partial response) was achieved. Additionally, 16 patients (45.7 %) had disease stabilization. The median time-to-progression was 6 months (95 % confidence interval, 4-8) and the median overall survival was 17 months (95 % confidence interval, 12-22). Grade 3-4 hematologic toxicities were as follows: leucopenia (14.3%), neutropenia (8.6%), and anemia (2.9%). One febrile neutropenic episode (2.9%) was observed. Non-hematologic toxicity was well tolerated and easily managed and no grade 3-4 palmoplantar erytrodysestesia (PPE) was observed. CONCLUSION: The combination of gemcitabine and PLD is an effective and tolerable treatment option, with 74.3 % disease control rate for patients with platinum resistant/refractory ovarian cancer.

Vinorelbine in combination with carboplatin followed by single-agent consolidation therapy for unresectable localized or metastatic non-small-cell lung carcinomas.

BACKGROUND: Adding more than four cycles of the combination regimen increase toxicities. The availability of an intravenous (i.v.) and oral form of vinorelbine appeared as a particularly convenient way to provide a consolidation treatment to patients who have achieved an objective response or stable disease. PATIENTS AND METHODS: This study was retrospectively designed to investigate the efficacy in terms of response and safety of i.v. vinorelbine 25 mg/m(2) on day 1 and oral vinorelbine 60 mg/m(2) on day 8 given with carboplatin area under the curve (AUC) 5 once every 3 weeks (q3w) for four cycles followed by consolidation therapy with single-agent vinorelbine in non-progressive patients with advanced non-small-cell lung cancer (NSCLC). RESULTS: Seventy-two patients enrolled into the study from October 2006 to July 2009 received the combination regimen. Thirty-seven patients (51.3%) also received the subsequent consolidation treatment. Partial tumor responses were obtained in 25 patients (34.7%) of 72 evaluable patients. Stable disease was observed in 26 (36.1%) of patients. The median progression free-survival was 4 months (95% CI 3.1-4.8). The median overall survival time was 10 months (95% CI 8.2-11.7) and the 1 year survival was 38.1%. The main toxicities recorded were hematological. Grade 3-4 neutropenia were observed in 17 patients (23.6%). Only two patients experienced grade three febrile neutropenia in the induction period, and there was no occurrence of febril neutropenia in the consolidation period. Nausea and vomiting were the major non-hematological toxicities reported. Toxicities occurred primarily during the initial combination phase of the chemotherapy. CONCLUSIONS: Despite the low dose of vinorelbine (25mg/m(2) i.v. on day 1 and only 60 mg/m(2) oral on day 8, every 3 weeks) achieved during the study, the response rate of 34.7%, the disease control of 70.8% and the 10 months median overall survival with tolerable toxicity profile, confirmed that this combination, offers an active and safe regimen for patients with advanced NSCLC.

Prognostic importance of COX-2 expression in patients with colorectal cancer.

A relationship between cyclooxygenase-2 (COX-2) expression and the pathogenesis of colorectal cancer has been reported in recent studies. Moreover, it has been indicated that COX-2 expression may have a prognostic role in colorectal cancer patients. In this study, we investigated the prognostic significance of COX-2 expression in 83 patients with colorectal cancer. COX-2 expression was assessed using immunohistochemical methods and was evaluated by grading both staining intensity and staining extension. The relationships between COX-2 expression and clinicopathological features of the patients and patient survival were evaluated. There was no relationships between COX-2 expression and tumor size (tm < 3 cm or tm > or = 3 cm), tumor histopathological differentiation (poorly differentiated or moderately + well differentiated), number of metastatic lymph nodes (< 4 or 3 > or = 4), histopathology of the tumor, localization of the tumor (colon or rectum), distant metastasis, and vascular invasion of the tumor. In the multivariate analysis, COX-2 expression was not found as an independent prognostic factor. We demonstrated that COX-2 expression was not correlated with clinicopathological characteristics of colon carcinoma and disease outcome.

Prognostic value of serum IL-18 and nitric oxide activity in breast cancer patients at operable stage.

Interleukin-18 (IL-18) is a multifunctional cytokine that was previously termed interferon-gamma-inducing factor. It has been suggested that serum IL-18 level may be used as a prognostic factor in some cancer types. Nitric oxide is a potent biologic molecule involved in the pathogenesis of cancer. In this study, we measured serum IL-18 and nitrate + nitrite levels in 56 patients with nonmetastatic breast cancer and 14 control subjects. Serum IL-18* and nitrate + nitrite** levels were significantly higher in patients with breast cancer when compared to the control subjects (*p < 0.05, **p < 0.001). Serum IL-18 levels were significantly higher in patients whose tumor size was greater than or equal to 5 cm when compared to patients whose tumor size was less than or equal to 2 cm (p < 0.05). Patients who were axillary lymph node negative (ALN) had lower serum IL-18 levels when compared to patients with positive ALN (p < 0.001). Serum IL-18 levels were significantly higher in patients with stage IIB or IIIA when compared to patients with stage I or IIA (p < 0.05). There was no significant difference in serum nitrate + nitrite levels in terms of age, tumor stage, estrogen receptor, and menopausal and ALN status (p > 0.05). In conclusion, serum IL-18 level may be a useful marker to predict prognosis of patients with breast cancer in complete remission after surgery. Long-term follow-up is required to clarify this hypothesis.