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Background: The development of brain metastases (BMs) was associated with poor prognosis in melanoma patients. Patients with BMs have a median survival of <6 months. Melanoma is the third most common tumor to metastasize to the brain with a reported incidence of 10-40 %. Our aim was to identify factors predicting development of BMs and survival. Patients and methods: We performed a retrospective analysis of 470 melanoma patients between 2000 and 2012. The logistic regression analyses were used to identify the clinicopathological features of primary melanoma that are predictive of BMs development and survival after a diagnosis of brain metastases. Results: There were 52 patients (11.1 %) who developed melanoma BMs during the study period. The analysis of post-BMs with Kaplan-Meier curves has resulted in a median survival rate of 4.1 months (range 2.9-5.1 months). On logistic regression analysis site of the primary tumor on the head and neck ( p = 0.002), primary tumor thickness (Breslow >4 mm) ( p = 0.008), ulceration ( p = 0.007), and pathologically N2 and N3 diseases ( p = 0.001) were found to be significantly associated with the development of BMs. In univariate analysis, tumor thickness and performance status had a significant influence on post-BMs survival. In multivariate analysis, these clinicopathologic factors were not remained as significant predictive factors. Conclusions: Our results revealed the importance of primary tumor characteristics associated with the development of BMs. Ulceration, primary tumor thickness, anatomic site, and pathologic ≥N2 disease were found to be significant predictors of BMs development. [ABSTRACT FROM AUTHOR]

Purpose: Combinations of trastuzumab with paclitaxel or capecitabine are effective therapies in human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC). This retrospective study evaluated the efficacy and toxicity of trastuzumab and paclitaxel plus capecitabine in the first-line therapy for patients with HER2-positive MBC. Methods: A total of 40 patients with HER2-positive MBC treated between January 2008 and January 2011 were evaluated retrospectively in 6 institutions. Three patients with performance score of 3 who died before response assessment were excluded from the study. The patients were given trastuzumab 8 mg/kg loading dose followed by then 6 mg/kg dose on day 1 and paclitaxel 175 mg/m on day 1 plus capecitabine 825 mg/m twice daily on days 1-14 every 3 weeks. Results: A total of 287 cycles of chemotherapy were administered with a median of 8 treatment cycles per patient (range 3-12). Median follow-up period was 24.7 months (range 4.7-51). There were 9 patients (24.3 %) with complete responses, 21 (56.8 %) with partial responses, 4 (10.8 %) with stable disease and 3 (8.1 %) with progressive disease resulting in an overall response rate (ORR) of 81.1 %. Median progression-free survival and overall survival were 14 and 38.4 months, respectively. Rates of grade 3 adverse events were neutropenia ( n = 4, 10.8 %), cardiac dysfunction ( n = 1, 2.7 %), hand-foot syndrome ( n = 2, 5.4 %), nausea ( n = 2, 5.4 %), vomiting ( n = 2, 5.4 %), fatigue ( n = 1, 2.7 %), diarrhea ( n = 1, 2.7 %), neuropathy ( n = 1, 2.7 %) and alopecia ( n = 1, 2.7 %). Conclusions: Combination of trastuzumab and paclitaxel plus capecitabine is an effective and well-tolerated regimen in the first-line therapy for women with HER2-positive MBC. [ABSTRACT FROM AUTHOR]

Purposes: The overall prognosis for recurrent malignant glioma (MG) is extremely poor, and treatment options are limited. We evaluated our multicenter retrospective experience for patients with recurrent MG administering bevacizumab and irinotecan in combination therapy. Methods: A total of 115 patients with grade IV glial tumor ( n = 93) and grade III glial tumor ( n = 22) were retrospectively evaluated at 14 centers in Turkey. Primary objectives of the study were to evaluate the efficacy and toxicity of the bevacizumab and irinotecan as salvage treatment based on response to therapy, progression-free survival (PFS), 6 months of PFS, overall survival (OS), and 6 months of OS (OS6). Results: Bevacizumab and irinotecan were performed as second line (79.1 %) and third line treatment (20.9 %). Median chemotherapy cycle was 6 (range 1-37), and median follow-up was 6 months (range 1-36 months). Objective response rate was 39.1 %. Six-month PFS and OS6 were 46.3 % and 67.5 %, respectively. Median PFS was 6 months (95 % CI 2.5-9.5) and 6 months (95 % CI 4.9-7.1) in the grade III and IV groups, respectively ( p = 0.773). Median OS was 9 months (95 % CI 7.1-10.9) and 8 months (95 % CI 6.6-9.4) in the grade III and IV groups, respectively ( p = 0.450). Serious toxicities were observed in 7.8 % of patients. Treatment-related toxic death was observed in 3 patients. There was no treatment related to central nervous system hemorrhage or other serious hemorrhages. Conclusions: Present study results were consistent with previous studies. In addition, we detected similar outcomes in grade III and IV glial tumors. [ABSTRACT FROM AUTHOR]

Purposes: Trastuzumab is known to be effective for early and advanced stages of breast cancer but optimal duration for early-stage breast cancer (EBC) is not well known. We evaluated the efficacy and toxicity of 9- and 52-week trastuzumab therapy for EBC retrospectively. Methods: In this multicenter study, the medical records of all patients with EBC were analyzed in 8 centers retrospectively. Totally consecutive, 479 female patients who received trastuzumab in the adjuvant treatment were evaluated for disease-free survival (DFS), overall survival (OS), efficacy, and toxicity. Results: There were 181 (37.8 %) and 298 (62.2 %) patients in the 9- and 52-week trastuzumab groups, respectively. Median follow-up was 30.6 months (5.7-68.9) in the 9-week trastuzumab group and 29.3 months (5.9-59.6) in the 52-week trastuzumab group. Thirty-six month DFS was 90 and 85 % ( P = 0.132) in the 9- and 52-week trastuzumab treatment groups, respectively, and 36-month OS was 96 and 97 % in the 9- and 52-week trastuzumab groups, respectively ( P = 0.779). Symptomatic cardiotoxicity was observed in 1 (0.6 %) patient in the 9-week trastuzumab group and in 4 (1.3 %) patients in the 52-week trastuzumab group. Conclusions: In this study, similar outcomes were found in the 9- and 52-week trastuzumab treatment groups. [ABSTRACT FROM AUTHOR]

Purpose: 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. Patients and methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Bevacizumab-based chemotherapy has become the standard of care in metastatic colorectal cancer (MCRC). We aimed to measure the levels of serum soluble FAS, FASL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and its death receptors DR4 and DR5 in MCRC patients and to define prognostic significance of these parameters in response to bevacizumab in these patients. The levels of these parameters in serum samples were quantified by a commercially available ELISA kit in 31 MCRC patients before and after 2 cycles of therapy and 25 healthy controls. Pretreatment sFAS levels in MCRC patients was significantly lower than the levels of controls ( p = 0.043). There was no significant difference in sFAS and sFASL levels in MCRC patients before and after bevacizumab-based treatment. There was no significant difference in sFAS/sFASL ratio in MCRC patients before and after treatment and controls. Soluble DR5 levels were significantly higher in pretreatment serum samples compared with controls ( p = 0.008). However, pretreatment sTRAIL and sDR4 levels were similar to the levels of controls. There was no significant difference in sTRAIL, sDR4, and sDR5 levels in MCRC patients before and after treatment. When patients were grouped according to treatment response (responders vs. non-responders), post-treatment sFAS/sFASL ratio was significantly lower in responding patients compared with non-responders ( p = 0.029). Significant correlations were observed between post-treatment sFASL and sDR4, sFAS and sTRAIL, sTRAIL and sFAS/sFASL ratio, and sFASL and sDR5. Non-significant changes in apoptotic markers with bevacizumab-based chemotherapy showed that they have no prognostic significance in MCRC patients. Significant change in sFAS/sFASL ratio according to treatment response could be an indicator of chemosensitivity. [ABSTRACT FROM AUTHOR]