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Alpha2-adrenoreceptor (α2-AR) is a noradrenergic receptor that is frequently studied for modulation of seizure activity. However, the precise role of this receptor agonists in regulating seizure activity is still unclear. Our aim in this study was to investigate the effects of α2-AR agonist dexmedetomidine (DEX) and atipamezole (α2-AR antagonist, ATI) on seziures in rats. In the study, 32 adult male Wistar Albino rats (weighing 220–260 g) were used. To induce seizures in rats, pentylenetetrazole (PTZ, 35 mg/kg) was injected intraperitoneally (i.p.) and seizure stages were determined according to the Racine scale. After induction of seizures, DEX (0.1 mg/kg, i.p.) and ATI (1 mg/kg, i.p.) were administered to rats and their effects determined on seizures. GABA levels of the brain hippocampal tissue sample were measured using an ELISA kit and c-Fos positive cells of the dentate gyrus and hippocampal regions were quantitatively analyzed with Image J software. The results showed that DEX decreased the seizure stages according to the Racine scale, significantly prolonged the onset time of first myoclonic jerk (FMJ) and reduced the number of spikes and percentage seizure duration (p

Histiocytic sarcoma (HS) is an extremely rare and aggressive hematopoietic tumor. Although it can be seen at any anatomic location, the most common primary sites are skin as extranodal region, locations including the lymph nodes and gastrointestinal tract. To the best of our knowledge, in light of PubMed search, this is the first primary tonsillar HS case presented with disseminated metastases at the time of diagnosis. A 58-year-old male patient applied with swelling on the right side of the neck, difficulty in swallowing, and weight loss. Positron emission tomography computed tomography was performed and increased pathological 18F fluorodeoxy D glucose uptake was detected in the right palatine tonsil, bilateral cervical multiple lymph nodes, liver masses, intra abdominal lymph nodes, and nodular lesion in the left adrenal gland. Tonsillectomy was performed and the pathological result was reported as HS. The patient did not respond to any treatment and had died after 5 months from the date of diagnosis. In conclusion, HS is generally diagnosed at advanced stage, it has limited chemotherapy response and high mortality rates. To understand this rare disease's pathophysiological and clinical features, further investigations are needed.

Soft tissue sarcomas, which originate from the mesenchymal tissue, represent a rare disease group with more than 100 subtypes. Primary treatment is surgical excision. In locally-advanced or metastatic cases, systemic treatment is the only therapeutic approach. Because of their heterogeneity, prognosis and response to the chemotherapy may be relatively different. Monotherapy with doxorubicin and its combination with ifosfamide continue to be the standard approach in the first-line treatment of advanced disease. Histology-directed therapy has become popular with the introduction of novel cytotoxic agents. Successful results have been achieved with recent developments in the field. Currently, the median overall survival rate in advanced stage disease barely exceeds 12 months in spite of the novel treatment options. In this review, our objective was to summarize the current data on cytotoxic treatments in the metastatic soft tissue sarcomas.

Tamoxifen plays a critical role in the treatment of hormone receptor-positive breast cancer. Despite these great benefits against breast cancer, tamoxifen increases the risk of endometrial pathologies such as endometrial hyperplasia, polyp, and neoplasms because of agonistic effect on endometrial tissues. Therefore, gynecologic follow-up should be carried out during tamoxifen treatment. Uterine tumors are frequently detected as the result of presentation with abnormal uterine bleeding. In addition, genital tract's metastases from distant primary tumors can present with abnormal uterine bleeding. Therefore, it is important to determine whether the uterine mass is metastatic or primary because different treatment modalities are used for them. In this context, breast carcinomas are the most frequent metastatic tumors, particularly invasive lobular carcinoma. Here, we report an invasive lobular carcinoma case that presented with abnormal uterine bleeding while receiving tamoxifen therapy and has metastasize in the uterus.

WOS: 000392824000012, PubMed ID: 27768606, The objectives of this study were to compare progression-free survival (PFS) with somatostatin analog (SSA) versus chemotherapy (CTx) in first-line therapy and to determine the patient group in which these treatments were more effective in neuroendocrine tumors (NETs) with a Ki-67 index of 20% or less. Patients who received SSA or CTx and had unresectable locally advanced and metastatic NETs with a Ki-67 index of 20% or less were retrospectively selected from 13 centers in the Turkish database between 2000 and 2015. One hundred and sixty-five patients were enrolled. The median age was 56 years and the male-to-female ratio was 1.09. Seventy-four (45%) patients were of grade 1 NET and 91 (55%) were of grade 2. SSA was given to 104 patients, whereas 61 were treated with CTx. The objective response rate after SSA was 15.4%; another 73.1% had stable disease. The objective response rate after CTx was 36.1%, and 40.9% had stable disease (P = 0.008). The median PFS in SSA patients was 21 months (95% confidence interval: 12.4-29.6), and 8 months for CTx (95% confidence interval: 5.5-10.6) (P < 0.001). There was no significant difference between PFS of receiving SSA and CTx in pancreatic neuroendocrine tumor (PNET) patients; however, the PFS of receiving SSA was longer in non-PNET patients (P < 0.001). SSA was better treatment in advanced NET patients with a Ki-67 index of less than 5%, having a primary resected and a performance status of 0 (P < 0.05). SSA may be preferred over CTx in advanced NET patients with low-to-intermediate grade. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

Most data on prognostic factors for patients with high-grade undifferentiated pleomorphic sarcoma (HGUPS) is obtained from analyses of soft tissue sarcomas. The purpose of this study was to evaluate the clinicopathologic features and their impact on outcomes specifically in patients diagnosed with HGUPS. In this multicenter trial, we retrospectively analyzed 112 patients who were diagnosed and treated at 12 different institutions in Turkey. We collected data concerning the patients, tumor characteristics, and treatment modalities. There were 69 males (61.6 %) and 43 females (38.4 %). Median age was 56 years (19–90). The most common anatomic site of tumor origin was the upper extremity. Pleomorphic variant was the predominant histological subtype. Median tumor size was 8.2 cm (0.6–30 cm). Tumors were mainly deeply seated (57.1 %). Fifty-seven patients (50.9 %) were stage II and the remainder were stage III at the time of diagnosis. Median follow-up was 30 months (2–160). The primary site of distant metastasis was the lung (73.5 %) and the second most common site was the liver (11.7 %). The 5-year overall survival, distant metastasis-free survival, and local recurrence-free survival rates were 56.3, 53.4, and 67.2 %, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of II (p = 0.033), deep tumor location (p = 0.000), and development of distant metastasis (p = 0.004) were negatively correlated with overall survival, and perioperative radiotherapy and negative microscopic margins were significant factors for local control rates (p = 0.000 for each). Deep tumor location (p = 0.003) was the only adverse factor related to distant metastasis-free survival. Deep tumor location, ECOG performance score of II, and development of distant metastasis carry a poor prognostic implication on overall survival. These will aid clinicians in predicting survival and treatment decision. © 2015, International Society of Oncology and BioMarkers (ISOBM).

BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings.METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants.FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [INTERPRETATION: At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events.FUNDING: Wyeth, Pfizer, and Puma Biotechnology.

WOS: 000408269300020 PubMed ID: 27670893 This is a multicenter study to assess the prognostic factors and adjuvant chemotherapy in patients with small bowel adenocarcinoma (SBA). A total of 78 patients with SBA diagnosed with completely resected SBA were involved in the study. Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection. Neither disease-free survival nor overall survival was found to be significantly improved by the adjuvant chemotherapy Background: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA. Materials and Methods: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty-eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1: 1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan-Meier estimates. Results: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow-up duration was 29 months. Three-year median disease-free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11-1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts. Conclusions: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection.

e15056 Background: Gastric cancer (GC) remains a common cancer in Turkey. There is increasing evidence of an association between obesity and risk of GC. Body mass index has been suggested to correl...

Purpose The aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab. Methods Medical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively. Results Median follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER− and PR−) tumor ( p = 0.001, RR: 3.4, 95% CI: 1.33–8.71) and stage 3 disease ( p = 0.0032, RR: 9.39, 95% CI: 1.33–8.71) were significant risk factors for development of brain metastasis as the first site of recurrence. Conclusions In patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER− and PR−) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.

Sorafenib is a multi-targeted tyrosine kinase receptor inhibitor used to treat patients with advanced gastrointestinal stromal tumors (GISTs). The present study evaluated the efficacy and tolerability of sorafenib therapy for patients with GISTs. Between January 2001 and November 2012, 25 patients, from multiple centers, who had received sorafenib as the third- or fourth-line treatment for GISTs were investigated retrospectively. In total, 17 patients were male and eight were female. The median age was 54.0 years (range, 16–82 years). From the patients, 21 received imatinib for longer than six months and four received it for less than six months. The clinical benefit rate of sorafenib was 40.0%. Treatment-related adverse events were reported in 72% of patients. These adverse events were generally mild to moderate in intensity. The median progression-free survival (PFS) and overall survival (OS) times of the patients who received sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage was an independent prognostic factor for PFS and OS. Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.

Medullary thyroid carcinoma (MTC) is an uncommon neuroendocrine tumor (NET) derived from the parafollicular C cells of the thyroid gland. Calcitonin secretion is a universal feature of the tumor. Approximately 25–30 % of the patients present with autosomal dominant hereditary forms as part of multiple endocrine neoplasia (MEN)—MEN-2A, MEN-2B, or familial MTC syndromes. RET proto-oncogene mutations are responsible for the pathogenesis. Hereditary forms are secondary to germline mutations in the RET gene with different penetration rates causing a diversity of disease phenotypes. Majority of the sporadic cases harbor somatic RET gene mutations, whereas about 5 % of those display germline RET gene mutations. Identification of patients genetically at high risk is critical, because affected individuals are best treated with early and prophylactic surgery. Surgical resection remains the principal treatment modality with total thyroidectomy and extended cervical lymph node dissection. Impact of radiotherapy and chemotherapy in the management of MTC is limited, and prognosis of progressive and metastatic disease remains dismal. Improved comprehension of the molecular alterations and discovery of pathways involved in the pathogenesis of MTC have led to the development of specific targeted inhibitors against tyrosine kinases that have changed the way metastatic disease is treated. Vandetanib and cabozantinib are approved by the FDA in the treatment of advanced MTC. Although much progress has been made, there exists an apparent “unmet medical need” for innovative therapeutic approaches in advanced MTC.

50th Annual Meeting of the American-Society-of-Clinical-Oncology -- MAY 30-JUN 03, 2014 -- Chicago, IL, WOS: 000358613200846, …, Amer Soc Clin Oncol

Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 mg/m(2) (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 mg/m(2) i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95% CI 2.65-3.34) and median overall survival (OS) was 6 months (95% CI 2.09-9.90) in the whole group. Median PFS was 3 months (95% CI 2.60-3.39) in group A vs 3 months (95% CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95% CI 2.47-9.53) in group A vs 12 months (95% CI 2.83-21.1) in group B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

e18510 Background: Aim of the study was to determine the relationship between clinicopathologic characteristics and treatment modalities for locally advanced thymic malignancies(TM). Methods: We retrospectively reviewed medical records of 107 patients(pts) who treated from 1992 to 2012 in medical oncology service of 7 tertiary hospital. 21 pts who presented metastatic disease and 31 pts who had early stage at the time of diagnosis were excluded. Results: A total of 55 patient’s data were analyzed. Median age was 46(17-73) years. Median follow-up was 33(1-103) months(mts). 65% of pts was male. Histopathologic diagnosis were as follows: thymoma type A-B2 ( TA-B2) 29 , thymoma type B3 (TB3) 10 and thymic carcinoma (TC) 16. 42 of pts underwent surgery, but total resection of the tumor have been achieved at only 28 pts(6 TC and 22 TA-B2 or TB3).30 pts have stage III diasease (mostly thymoma 23/30). 43 pts treated with mediastinal radiotherapy ( 21 adjuvant, 22 primary). A cisplatin containing regimen has been received 23 pts in the adjuvant setting. 31 pts were given as primary chemotherapy (ADOC, PAC and EP). Overall response rate was 81.6% with first-line chemotherapy. There was no apparent response in 3 pts(3/23) with thymoma and 4 pts(4/8) with TC. 20 pts have experienced a disease progression and 27 pts died ( 8 of these cases died from other unrelated causes). Median progression free survival was 45 (30-59)mts. Kaplan-Meier survival analysis estimated that overall survival of the pts with stage III disease were relatively longer than stage IVA ones, but it can not reach statistical significance (median 78 vs 45 mts,p=.11). Prognosis of TC pts were considerably worse than TB3 and TA-B2 (median 17 vs 45 vs 76 mts respectively,p=.01). Although there was no a statistical difference between pts who underwent total tumor removal and who did not, we have seen a trend toward better survival in pts who were suitable to triple modality therapy(median 79 vs 45 mts,p=.27). Conclusions: Cisplatin based chemo plus mediastinal radiotherapy may provide a chance of achieving a long-lasting remission in locally advanced TM. But, complete surgical removal of the tumor are still the mainstay of treatment.

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.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.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.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.

Background: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy has limited impact on overall survival (OS) so that eligible patients should be selected carefully. The aim of this study was to analyze prognostic factors for survival in Turkish advanced pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving gemcitabine (Gem) alone or gemcitabine plus cisplatin (GemCis). Methods: This retrospective evaluation was performed for patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and who received gemcitabine between December 2005 and August 2011. Twenty-seven potential prognostic variables were chosen for univariate and multivariate analyses to identify prognostic factors associated with survival. Results: Among the 27 variables in univariate analysis, three were identified to have prognostic significance: sex (p = 0.04), peritoneal dissemination (p = 0.02) and serum creatinine level (p = 0.05). Multivariate analysis by Cox proportional hazard model showed only peritoneal dissemination to be an independent prognostic factor for survival. Conclusion: In conclusion, peritoneal metastasis was identified as an important prognostic factor in metastatic pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving Gem or GemCis. The findings should facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

662 Background: Oxaliplatin and irinotecan in combination with 5-fluorouracil and leucovorin for metastatic colorectal cancer (mCRC) accepted as the standard treatment. There is no standard treatment approach for patients after progression with these agents. In this study aimed to evaluate the efficacy and side effects of patients with previously treated metastatic colorectal cancer a salvage combination with oral 5-fluorouracil (tegafur-uracil UFT) or Mitomycin C and Raltitrexed. Methods: In the 7 centers, data of 62 patients who received Raltitrexed 2.6 mg/m2 (max. 5 mg) (day 1) and UFT 500 mg/day (1-14. days), or Mitomycin C 6mg/m2 (day 1) every 3 weeks, with a diagnosis of metastatic colorectal cancer, between December 2008 and June 2013 has been analyzed retrospectively. Overall survival (OS), progression-free survival (PFS), and toxicity profiles were evaluated. Results: The median age of patients was 51 (min-max: 18-76 years), and 35 (56%) were male and 27 (44%) were female. Thirty nine patients (63%) had ECOG performance status 0 and 1. Four patients (10%) received a combination of UFT and Raltitrexed at the second line and 38 patients (90%) had third, fourth, and fifth lines. Otherwise Mitomycin C plus Raltitrexed protocol used at the second and third lines. Twelve patients (19%) developed grade 3/4 toxicities as diarrhea and fatigue and 13 patients (21%) needed to dose reduction. In all patients the median PFS was 3 months (%95 CI, 2,65–3,34) and the median OS was 6 months (%95 CI, 2,09–9,90). Two groups were evaluated separately; the median PFS was 3 months (%95 CI, 2,60–3,39) and median OS was 6 months (%95 CI, 2,47–9,53) in UFT arm and, the median PFS was 3 months (%95 CI, 1,64–4,35) and median OS was 12 months (%95 CI, 2,83–21,1) in Mitomycin C arm. Statistical significance could not be determined (p>0.05). Conclusions: Thecombination of Raltitrexed with UFT and Mitomycin C showed an acceptable survival time and toxicity in the treatment of patients with previously treated mCRC. It could be considered as a salvage treatment option in mCRC.

e14705 Background: The addition of bevacizumab to chemotherapy significantly shows survival advantage in metastatic colorectal cancer (mCRC), but with limited data about irinotecan combination in salvage therapy. Efficacy and toxicity of bevacizumab combination regimens were assessed in first-line and salvage therapies. Methods: Total of 1011 (659 in first-line and 352 in salvage) patients were retrospectively evaluated. Results: In first-line therapy, the ORR was 36.4%. Median PFS was 7 months for FOLFIRI, 6 months for IFL and 6 months for other chemotherapy regimens with a median overall PFS of 7 months. Median survival was 29 months for FOLFIRI, 28 months for IFL and 21 months for others with a median overall survival of 28 months. In salvage therapy, the ORR was 25.2%. Median PFS was 7 months for FOLFIRI, 7 months for IFL and 6 months for others with a median overall PFS of 7 months. Median survival was 19 months for FOLFIRI, 13 months for IFL and 21 months for others with a median overall survival of 19 months. The main toxicities in first-line and salvage therapy were neutropenia, febrile neutropenia, nausea and vomiting, diarrhea, mucositis, bleeding, hypertension, thromboembolism, fistulization and bowel perforation. Conclusions: Bevacizumab combination chemotherapy regimens are effective with a tolerable safety profile in mCRC patients in first-line and salvage therapy.

e12657 Background: Obesity is independently associated with breast cancer (BC) recurrence and poor prognosis despite therapy. However there is no data available about the effect of obesity on the n...