[Show abstract][Hide abstract] ABSTRACT: Docetaxel (DTX) is widely used for the treatment of metastatic prostate and breast cancers. Despite the clinical success of DTX, drug-related cumulative toxicity restricts its clinical use in cancer therapy. Thus, there is an urgent need for new therapeutic options. Octreotide (OCT) is a synthetic somatostatin analog that induces apoptosis in different cancer cell lines in vitro. In this study, we investigated the possible synergistic apoptotic effects of DTX in combination with OCT in prostate and breast cancer cell lines.
The XTT cell viability assay was used to determine cytotoxicity. Apoptosis was evaluated by Cell Death Detection ELISA(Plus) Kit. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Levels of SSTR2 and SSTR5 proteins were determined by western blot analysis.
DTX and OCT combination induced apoptosis in both breast and prostate cancer cells in a concentration- and time-dependent manner. Moreover, combination treatment resulted in inhibition of anti-apoptotic proteins such as Bcl-2 and Bcl-xL and induction of pro-apoptotic proteins Bax, Cytochrome c and IAPs in all of the tested cancer cell lines. SSTR2 and SSTR5 protein levels were induced as compared to any agent alone.
These results indicate that this combination treatment is a significant inducer of apoptosis in a synergistic manner in breast and prostate cancer cells. This strong synergism helps to lower the dose of DTX in both types of cancers, thus letting DTX to be used for longer periods by delaying resistance development and lesser side effects.
Cancer Chemotherapy and Pharmacology 04/2015; 75(6). DOI:10.1007/s00280-015-2756-1 · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy.
Asian Pacific journal of cancer prevention: APJCP 09/2014; 15(17):7119-23. DOI:10.7314/APJCP.2014.15.17.7119 · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.
Medical Oncology 09/2014; 31(9):152. DOI:10.1007/s12032-014-0152-z · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG) Abstract Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the fre-quency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopatho-logically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5–92), and the mean survival was 25.8 months (95 % CI 20.4–29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable ana-lysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27–4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.
[Show abstract][Hide abstract] ABSTRACT: The identification of clinical, biochemical and molecular markers to predict or monitor the efficacy of bevacizumab represents a major point in the treatment of patients with metastatic colorectal cancer. Studies and genetic analyses have been conducted to identify a predictive biomarker of bevacizumab efficacy. However, genes of the angiogenic pathway and angiogenic biomarkers vary substantially, thereby causing interindividual differences that complicate the identification of predictors for anti-vascular endothelial growth factor drugs like bevacizumab. So, the current challenge in bevacizumab treatment is to find predictive markers and implement them in clinical practice. In this review we have summarized the potential candidate biomarkers that may have a role in identifying patients who benefit most from bevacizumab treatment.
[Show abstract][Hide abstract] ABSTRACT: Background: Unlike for fit elderly metastatic colorectal cancer (mCRC) patients, general approaches to initial treatment for the frail older mCRC patients are not clear. Our aim was to evaluate the efficiency and safety of first-line single-agent treatment in one such group. Materials and Methods: We retrospectively evaluated mCRC patients aged 70 or older with an Eastern Cooperative Oncology Group performance score of 2. They had no prior treatment and underwent first-line single-agent capecitabine or other monotherapies until disease progression or unacceptable toxicity. Results: Thirty-six patients were included. Most (n:28, 77.8%) were treated with capecitabine. One patient achieved a complete response and 5 patients had a partial response for an overall response rate of 16.6%. Twelve patients (33.3%) remained stable. Median progression free survival was 5 months (confidence interval (CI), %; 3.59-6.40) and median overall survival was 10 months (95 CI%; 8.1-11.8). Grade 3-4 toxicity was found in 6 patients (16.6%). Febrile neutropenia was not observed and there were no toxicity-associated deaths. Conclusions: Capecitabine is a safe chemotherapeutic agent with moderate activity for first-line treatment of older metastatic colorectal cancer patients with limited performance status.
Asian Pacific journal of cancer prevention: APJCP 04/2014; 15(7):3157-61. DOI:10.7314/APJCP.2014.15.7.3157 · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. A high-risk group of patients with stage II colon cancer has been identified by the results of studies in Western populations. The aim of this study was to investigate the prognostic factors of adjuvant chemotherapy in Turkish patients with stage II colon cancer.Methods. A total of 554 stage II colon cancer patients were retrospectively enrolled in the study. Three hundred fifty-three patients had received adjuvant chemotherapy (5-FU-LV, FOLFOX or FLOX) and 201 had received no adjuvant chemotherapy. T4 tumor stage, lymphovascular invasion, perineural invasion, bowel obstruction and/or perforation, <12 harvested lymph nodes, and poor differentiation were defined as high-risk factors. Results. The median age of the patients was 62 years (range 26-88). The median disease-free survival (DFS) was 58.1 months (95% CI, 47.6 months to 68.5 months) in the non-treatment group and has not been reached in the treatment group (P <0.01). In univariate analysis, patient age >60 years and T4 tumor stage were statistically significant factors that affected DFS as poor prognostic factors. Adjuvant chemotherapy reduced the risk of recurrence with statistical significance (P <0.01). In multivariate analysis, patient age >60 years and T4 tumor stage were independent risk factors affecting DFS. In addition, adjuvant chemotherapy was an independent favorable prognostic factor for DFS (P <0.01). Conclusions. Clinical and pathological risk factors in patients with stage II colon cancer may be different in the Turkish population compared to other populations. Further prospective studies in colon cancer are needed to understand the differences in biology and risk factors between races.
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) is among the most frequently diagnosed cancers and a major cause of cancer-related mortality worldwide. The aim of the present study was to determine whether there was an improvement in the time to disease progression (TTP) in patients with metastatic colorectal cancer (mCRC) treated with first-line bevacizumab plus chemotherapy, according to tumor characteristics and metastatic sites. Tumor characteristics and tumor burden were considered to be predictive markers of the therapeutic efficacy of bevacizumab. The medical records of 705 patients with mCRC were retrospectively reviewed in three oncology centers between January, 2005 and September, 2012. A total of 101 patients completed their first-line bevacizumab-containing treatment. The median TTP was 6.93 months [interquartile range (IQR)=4.20-9.80 months] in patients treated with irinotecan, 5-fluorouracil (5-FU) and bevacizumab vs. 7.42 months (IQR=6.08-10.68 months) in those treated with oxaliplatin, 5-FU and bevacizumab (P=0.589). When we compared patients with pulmonary metastases (median TTP, 9.9000 months) or other metastatic patients without pulmonary metastasis (median TTP, 6.9000 months), we observed a statistically significant difference (P=0.046). However, when the efficacy of bevacizumab was compared in terms of other tumor characteristics (tumor grade, size and lymph node involvement) and metastatic sites, the differences were not significant (P>0.05). We concluded that bevacizumab may be effective in all subgroups of patients with mCRC. Furthermore, bevacizumab with combination chemotherapy may be superior to combination chemotherapy only as the first-line treatment of patients with mCRC and pulmonary metastasis.
Molecular and Clinical Oncology 01/2014; 2(1):166-170. DOI:10.3892/mco.2013.212
[Show abstract][Hide abstract] ABSTRACT: PurposeWe aimed to investigate the improvement in symptoms, quality of life, patient and family satisfaction with care, and direct costs resulting from a palliative care program based case management model.Methods
The research was implemented at the Medical Oncology Clinic hospital of a University between September 2009 and September 2011. The research sample consisted of a total of 44 patients (22 control and 22 intervention group). The research tools were the Edmonton Symptom Diagnosis System, the Karnofsky Performance Scale, the EORTCQLQ-C30 Quality of Life Scale, a patient and family satisfaction form, and a patient cost record form.ResultsThe difference between total symptom mean scores and the sub-dimension symptoms of pain, fatigue, nausea, depression, anxiety, lack of appetite, lethargy, well-being, dyspnea, and constipation post-hospitalization and post-discharge of patients in the control and experimental groups were found to be statistically significant (p < 0.05). The level of decrease in symptom severity in the experimental group patients was more than in the control group (p < 0.000). The satisfaction level of patients and family in the palliative care based case management service was higher than that for conventional service in the control group (p < 0.05). No statistical difference was detected between the experimental and control groups regarding health costs and duration of hospitalization (p > 0.05).Conclusion
We provided a better symptom control, improved the patient s quality of life (excluding physical and congnitive functions), and patient and family satisfaction levels were higher in the palliative care based case management intervention group, but direct health costs were not affected.
The American journal of hospice & palliative care 10/2013; 31(6). DOI:10.1177/1049909113506980 · 1.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: The purpose of our study was to evaluate the perioperative complications, toxicity, mortality rates after cytoreductive surgery (CRS), and effects of hyperthermic intraperitoneal chemotherapy (HIPEC) used in the treatment of peritoneal surface malignancies. METHODS: Between September 2007 and March 2012, we performed 118 CRS and HIPEC with the closed abdominal technique on 115 patients with peritoneal carcinomatosis (PC). Systemic toxicities were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria and were analyzed from a prospectively collected database. RESULTS: The mean age of patients was 53.4 (range, 20-82) years; 76.3 % were female. PC was synchronous to primary cancer in 53.4 % of patients, metachronous in 41.5 %, and recurrent in 5.1 % of the patients. PCI was ≥15 in 53.4 % of the patients, and CC-0 cytoreduction was achieved in 68.5 % of the patients. Perioperative mortality was observed in 9 (7.6 %) patients. A total of 98 complications were observed in 46 (39.0 %) patients, and 4 patients underwent 6 reoperations for perioperative surgical complications. We observed toxicity in 25.4 % of the patients, nephrotoxicity in 18.6 %, and hematological toxicity in 13.6 % of patients. No significant difference was observed among age, gender, PCI and CC scores, origin of the primary tumor, and occurrence of toxicity and surgical complications. Prolonged operation times resulted in higher complication and/or toxicity rates (P < 0.01). CONCLUSIONS: Cytoreductive surgery and HIPEC is a combined treatment strategy for peritoneal surface malignancies with acceptable complication and toxicity rates.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Albeit the majority of gastric cancers occur at advanced age, little is known regarding the optimal systemic treatment of elderly patients with advanced gastric cancer (AGC). Methods: Patients with AGC who were ≥ 65 years old and were treated with carboplatin (area under the curve/AUC 5,on day 1, every 3 weeks) plus docetaxel (75 mg/m(2), on day 1, every 3 weeks) at 3 institutions were included in this retrospective analysis. The efficacy and the safety data of the regimen were analyzed. Results: A total of 30 patients were enrolled. They received 128 cycles of chemotherapy, with a median of 4 cycles (range 2-8). Complete response (CR) and partial response (PR) were observed in 2 (6.7%) and 10 patients (33.3%), respectively, amounting to an overall objective response rate (ORR) of 40%. Seven patients (23.3%) had disease stabilization (SD), and 11 (36.7%) showed disease progression (PD). The most common grade 3-4 toxicity was neutropenia occurring in 19 patients (63.3%). The mean progression-free survival (PFS) was 6.0 ± 0.5 months (95% CI: 5.0-7.4), and the mean overall survival (OS) 12.0 ± 1.0 months (95% CI: 9.2-12.1). Conclusion: Carboplatin plus docetaxel seems to be an active and well-tolerated regimen, representing a valuable alternative to cisplatin- and/or fluoropyrimidine-containing regimens for the treatment of elderly patients with AGC.
Journal of B.U.ON.: official journal of the Balkan Union of Oncology 11/2012; 18(1):147-53. · 0.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES • To investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the serine/threonine protein phosphatase inhibitors calyculin A (CA) and okadaic acid (OA) in hormone and drug refractory prostate cancer cells, PC-3 and DU-145. • To discover the effect of these combination treatments on phosphatase 1 (PP1) and PP2A protein expression levels in prostate cancer cells. MATERIALS AND METHODS • An XTT cell viability assay was used to determine cytotoxicity. • Apoptosis was evaluated by enzymelinked immunosorbent assay (ELISA) using a Cell Death Detection ELISA Plus Kit and verifi ed by measuring caspase 3/7 enzyme activity. • The PP1 and PP2A enzyme activities were evaluated by serine/threonine phosphatase ELISA and expression levels of PP1 and PP2A proteins were then re-assessed by Western blot RESULTS • Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis compared with any agent alone in both PC-3 and DU-145 prostate cancer cells. • The combination of ZA with phosphatase inhibitors resulted in enhanced suppression of both PP1 and PP2A enzyme activity andprotein levels, which was more overt with the ZA/CA combination. CONCLUSION • Results from our study increase the translational potential of our in vitro fi ndings and offer the basic rationale for the design of new combinatory strategies with ZA and phosphatase inhibitors for the treatment of prostate cancer, which may become resistant to conventional therapy.
BJU International 08/2012; 110(11c). DOI:10.1111/j.1464-410X.2012.11392.x · 3.13 Impact Factor