Joon Oh Park

Sungkyunkwan University, Sŏul, Seoul, South Korea

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Publications (137)513.24 Total impact

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    ABSTRACT: The benefit of adjuvant chemotherapy for patients with locally advanced rectal cancer who have received neoadjuvant concurrent chemoradiation therapy (CCRT) and undergone curative resection remains unclear. This study was a retrospective review of prospectively collected data. Patients with locally advanced rectal cancer who underwent curative surgery after neoadjuvant CCRT between January 2006 and March 2011 were identified. Four hundred forty-one patients who completed adjuvant chemotherapy (chemo group) were compared with 35 patients who did not receive any adjuvant treatment (nonchemo group). The 5-year disease-free survival (DFS) was significantly higher in the chemo group (78.5% vs. 63.1%, P = 0.016). After stratification of the patients according to nodal status, these differences were no longer significant, but there were trends toward inferior DFS in the nonchemo group in all survival curves. In multivariate Cox regression analysis, no adjuvant chemotherapy (HR, 2.306; 95% CI, 1.101-4.829; P = 0.027) emerged as an independent prognostic factor associated with decreased DFS. Adjuvant chemotherapy was significantly associated with increased DFS among patients who had undergone neoadjuvant CCRT and radical resection for locally advanced rectal cancer. Adjuvant chemotherapy should be considered in every patient after neoadjuvant CCRT irrespective of the final pathology stage. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 12/2014; · 2.64 Impact Factor
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    ABSTRACT: The aims of this study were to demonstrate the tumorigenicity of CD133+ colon cancer cells in vitro, analyze the correlations between spheroid formation and clinicopathologic variables, and screen for overexpressed genes in CD133+ colon cancer stem cells. Moreover, the aim of this study was to establish a living tumor tissue bank using surgically resected specimens. Using LoVo cell line, we isolated CD133+ cells and performed clonogenic assay and animal experiment to test tumorigenicity of CD133+ cells. Twenty-nine surgical samples were freshly collected from 27 patients who received curative or palliative surgery, and the samples were mechanically and enzymatically dissociated into single cells. We confirmed the enhanced tumorigenicity of CD133+ cells isolated from LoVo cell line both in vitro and in vivo. Of these 29 samples, 8 (28%) contained >3% CD133+ cells. Sphere formation was significantly higher in samples from patients with lymphatic invasion than in those without lymphatic invasion [54.5% (6/11) vs. 12.5% (2/16); P=0.033] and in samples containing >3% of CD133+ cells than in those containing ≤3% of CD133+ cells [36.4% (4/11) vs. 0% (0/16); P=0.019]. These findings indicate that CD133 is a valid marker for identifying cancer stem cells from fresh surgically resected colorectal cancer tissues. Furthermore, we successfully established a living tumor tissue bank using surgically resected colorectal tissues with a viability of >70%.
    Journal of gastrointestinal oncology 12/2014; 5(6):447-456.
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    ABSTRACT: Purpose: We retrospectively analyzed the feasibility and adverse events for two regimens, postoperative chemoradiation (CRT) with 5-fluorouracil/leucovorin (5-FU/LV) compared to S-1 in D2-resected gastric cancer patients. Patients and Methods: The study included 405 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection and received adjuvant therapy between January 2008 and July 2009. Feasibility and adverse events for the CRT and S-1 regimens were analyzed. Results: Out of the 405 patients, 244 (60.2%) had CRT and 161 (39.8%) had S-1 treatment. The regimen was selected based on the preferences of the physician and the patient. S-1 was more frequently administered to patients with older age (age ≥70) and those with early-stage disease (stage II). The stage was significantly more advanced in the CRT group compared to the S-1 group (S-1 vs. CRT: stage II, 59.6% vs. 36.1%; stage III/IV, 28.0% vs. 48.3%, respectively; p<0.001). The completion rate of the planned therapy was significantly higher in the CRT group than in the S-1 group (95.1% vs. 72.8%, respectively; p<0.001). Regarding severe adverse events (grade 3-4), neutropenia (CRT vs. S-1; 40.2% vs. 8.7%, respectively, p<0.001), nausea (CRT vs. S-1; 5.7% vs. 0%, respectively; p=0.002) and stomatitis (CRT vs. S-1; 7.4% vs. 2.5%, respectively; p=0.034) were significantly more frequent in the CRT cohort compared to the S-1 group. Conclusion: Both adjuvant CRT with 5-FU/LV and adjuvant S-1 are safe and feasible in D2-resected gastric cancer patients. Patients with old age or early stage disease tend to prefer S-1 therapy to chemoradiation.
    Anticancer research 11/2014; 34(11):6585-6591. · 1.71 Impact Factor
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    ABSTRACT: This study investigated the outcomes of salvage radiation therapy (RT) for isolated local recurrence of extrahepatic cholangiocarcinoma (EHCC) after radical surgery.
    Annals of Surgical Oncology 10/2014; · 4.12 Impact Factor
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    ABSTRACT: Background The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy. Methods In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3–4N0) or III (ypTanyN1–2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m2 and leucovorin 20 mg/m2 on days 1–5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov, number NCT00807911. Findings Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4–50·6). 3-year disease-free survival was 71·6% (95% CI 64·6–78·6) in the FOLFOX group and 62·9% (55·4–70·4) in the fluorouracil plus leucovorin group (hazard ratio 0·657, 95% CI 0·434–0·994; p=0·047). Any grade neutropenia, thrombocytopenia, fatigue, nausea, and sensory neuropathy were significantly more common in the FOLFOX group than in the fluorouracil plus leucovorin group; however, we noted no significant difference in the frequency of these events at grade 3 or 4. The most common grade 3 or worse adverse events were neutropenia (38 [26%] of 149 patients in the fluorouracil plus leucovorin group vs 52 [36%] of 146 patients in the FOLFOX group), leucopenia (eight [5%] vs 12 [8%]), febrile neutropenia (four [3%] vs one [<1%]), diarrhoea (four [3%] vs two [1%]), and nausea (one [<1%] vs two [1%]). Interpretation Adjuvant FOLFOX improves disease-free survival compared with fluorouracil plus leucovorin in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision, and warrants further investigation. Funding Korea Healthcare Technology R&D Project (South Korean Ministry of Health and Welfare).
    The Lancet Oncology 10/2014; · 25.12 Impact Factor
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    ABSTRACT: Pazopanib is an orally bioavailable, ATP-competitive, multi-targeted kinase inhibitor mainly targeting VEGFR2 and PDGFR tyrosine kinases, but the biological sequences of pazopanib activities beyond anti-angiogenesis are poorly defined. We used a panel of 38 GC cell lines in order to test the efficacy of pazopanib. In a growth inhibition assay, genomic changes indicated that pazopanib had differential effects on cell growth. Treatment of the KATO-III, OCUM-2M, SNU-16 and HSC-39 GC cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 - 2.0 microM, while the same treatment of those cell lines without FGFR2 amplification had no growth inhibitory effects. In the ectopic FGFR2-expressing model, treatment with the indicated concentrations of pazopanib significantly inhibited cell growth and colony formation by FGFR2-expressing NIH 3T3 cells with WT FGFR2 and mutant FGFR2 (S252W). Pazopanib also selectively suppressed constitutive FGFR2 signaling and phosphorylation of downstream effectors. In cell cycle analysis, FGFR2-amplified cells underwent cell cycle arrest at the G1-S phase after pazopanib treatment, whereas there were no significant effects on cell cycle progression in cells without FGFR2 amplification treated with pazopanib. In addition, pazopanib increased a substantial fraction of sub-G1 only in FGFR2-amplified cells. These findings show that the activation of FGFR2 signaling by amplification may be a critical mediator of cell proliferation in a small subset of GC patients and that pazopanib may provide genotype-correlated clinical benefits beyond the setting of highly vascular tumors.
    Molecular Cancer Therapeutics 09/2014; · 5.60 Impact Factor
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    ABSTRACT: We aimed to the addition of synthetic 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin to capecitabine-cisplatin (XP) in patients with previously untreated advanced gastric cancer (AGC).
    European journal of cancer (Oxford, England: 1990) 09/2014; · 4.12 Impact Factor
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    ABSTRACT: Capecitabine is known to increase mean corpuscular volume (MCV). To define the incidence of capecitabine-induced macrocytosis and its association with chemotherapy outcomes, we investigated data of 89 patients with advanced gastric cancer (AGC) who were enrolled in a randomized chemotherapy trial involving capecitabine.
    Cancer research and treatment : official journal of Korean Cancer Association. 08/2014;
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    ABSTRACT: Growth factor receptors, often carrying tyrosine kinase activities in their cytoplasmic domains, are overexpressed in many cancers. Coactivation of receptor tyrosine kinases (RTKs) plays a critical role in tumor response to targeted therapeutics. We examined concomitant overexpression of EGFR and MET in patients with HER2+ and HER2- gastric cancers (GCs). Tissue microarray samples obtained from 1,589 GC patients who received R0 gastrectomy with extensive node dissection and adjuvant chemoradiationtherapy were analyzed by immunohistochemistry and fluorescence in situ hybridization. HER2+ was observed in 169 patients (11%). Out of 169 HER2+ patients, 15 (9%) were EGFR+ and MET+, 29 (17%) were EGFR+, 37 (22%) were MET+, and the remaining 88 patients (52%) were HER2+ only, without concomitant EGFR or MET overexpression. Greater number of overexpressed RTKs correlated with younger age (p<0.001), larger tumor size (p=0.027), intestinal histology (p<0.001), and shorter overall survival (p=0.002). The mean overall survival was 113 months for HER2-/EGFR-/MET- and 63 months for HER2+/EGFR+/MET+ subgroups. Patients with HER2+/EGFR+/MET+ GCs had a substantial risk of death with a hazard ratio of 3.01 (95% CI, 1.54–5.90), compared to HER2-/EGFR-/MET- GC patients. Using patient-derived tumor cell models isolated from pericardial effusion of HER2+ and MET+ GC cases, we demonstrated that the combination of HER2-inhibitor (lapatinib) and MET-inhibitor offered a more profound inhibition in the ERK/AKT pathway and cell proliferation than lapatinib alone. Co-overexpression of RTKs was demonstrated in small subsets of GC associated with aggressive behavior, and in these cases, combination therapy may be considered as potential treatment options. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2014; · 6.20 Impact Factor
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    ABSTRACT: This study aimed to evaluate the prognostic significance and predictive performance of volume-based parameter of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in biliary tract cancer (BTC). Of the 268 patients who were enrolled onto phase III gemcitabine/oxaliplatin (GEMOX) versus GEMOX/erlotinib trial, a total of 48 patients had pretreatment (18)F-FDG PET/CT available for analysis. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis for the primary tumor were measured. The prognostic significance of these parameters and clinicopathological variables was assessed by Cox proportional hazards regression analysis. A cutoff of 98.8 ml for the MTVliver was the best discriminative value for predicting overall survival (>9 months). Multivariate analyses with adjustments for age, performance status, and disease status showed that only MTVliver was an independent prognostic factor associated with overall survival (HR 2.149, 95 % CI 1.124-4.109, P = 0.021). SUVmax did not show any correlation with overall survival. For patients in the high-MTVMBP group, overall survival was longer in the chemotherapy plus erlotinib group than in the chemotherapy-alone group [median 8.3 months (5.5-11.1) vs. 4.0 months (0.0-8.0); P = 0.048]. MTV may be considered as a significant independent metabolic prognostic factor for overall survival in patients with BTC and predictive marker for the selection of patients for the addition of erlotinib to first-line chemotherapy.
    Medical Oncology 07/2014; 31(7):23. · 2.15 Impact Factor
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    ABSTRACT: Trametinib, an oral mitogen/extracellular signal-related kinase (MEK)1/2 inhibitor, holds promise for malignancies with rat sarcoma (RAS) mutations, like pancreas cancer. This phase II study was designed to determine overall survival (OS) in patients with pancreas cancer treated with trametinib and gemcitabine. Secondary end-points included progression-free survival (PFS), overall response rate (ORR) and duration of response (DOR); safety end-points were also assessed.
    European journal of cancer (Oxford, England: 1990) 06/2014; · 4.12 Impact Factor
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    ABSTRACT: To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases.
    Radiation oncology journal. 06/2014; 32(2):77-83.
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    ABSTRACT: Although, gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to that of Western countries. However, there is no Korean multidisciplinary guideline for gastric cancer and thus, a guideline adequate for domestic circumstances is required. Experts from related societies developed 22 recommendation statements for the diagnosis (n=9) and treatment (n=13) based on relevant key questions. Evidence levels based on systematic review of literatures were classified as five levels from A to E, and recommendation grades were classified as either strong or weak. The topics of this guideline cover diagnostic modalities (endoscopy, endoscopic ultrasound, radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, radiotherapy) and pathologic evaluation. External review of the guideline was conducted at the finalization phase. (Korean J Gastroenterol 2014;63:66-81).
    The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 02/2014; 63(2):66-81.
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    ABSTRACT: Purpose Preclinical data has demonstrated the potential of simvastatin to overcome cetuximab resistance in KRAS mutant CRC patients. Therefore, we designed a study using simvastatin/cetuximab/irinotecan for KRAS mutant CRC patients who are refractory to irinotecan and oxaliplatin-based chemotherapy. Patients and methods In this phase II study, patients received 500 mg/m(2) cetuximab, 150-180 mg/m(2) (day 1), and 80 mg simvastatin (once daily, days 1-14, every 2 weeks). The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), the disease control rate (DCR), and safety. We also analyzed the relationship between the RAS gene expression signature score and treatment response to simvastatin/cetuximab/irinotecan. Results Fifty-two KRAS mutant CRC patients were enrolled. The ORR (complete response [CR], 0; partial response [PR], 1) was 1.9 % (95 % confidence interval [CI], -1.8-5.6). The DCR (CR, 0; PR, 1; stable disease, 33) was 65.4 % (95 % CI, 52.5-78.3). The median PFS and OS from the time of study drug administration were 7·6 months (95 % CI, 4.4-10.8) and 12.8 months (95 % CI, 9.5-16.2), respectively. The most common grade 3/4 adverse events were anemia (28.8 %), neutropenia (13.5 %), and diarrhea (7.7 %). The RAS signature score was significantly correlated with the maximal change in target lesions from baseline (r = 0.57, P = 0.014). Conclusion The simvastatin/cetuximab/irinotecan regimen showed promising efficacy and safety in KRAS mutant CRC patients who failed irinotecan and oxaliplatin-based chemotherapy. The RAS signature may be a novel predictor of treatment response to cetuximab-combined chemotherapy in CRC patients.
    Investigational New Drugs 01/2014; · 3.50 Impact Factor
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    ABSTRACT: The study aimed to determine the adequacy of the distal margin in patients having preoperative chemoradiotherapy followed by restorative surgery for rectal cancer. 368 patients with locally advanced rectal cancer treated for cure at our institution between July 1999 and March 2009 were included in the study. All underwent preoperative chemoradiotherapy (CRT) and sphincter-sparing surgery. The distal margin and other factors were examined for their effect on recurrence and survival. The median duration of follow-up was 48 months. The length of distal margin ranged from 0 to 9.0 cm (median 1.5 cm). The pelvic control and disease-free survival rates at 5 years for patients with a margin of ≤3 mm was no different from those in whom it was >3 mm (p = 0.6 and 0.8). The 5-year pelvic control rates between the ≤3 mm and >3 mm groups were 66.7% and 86.2% in patients with a ypT3-4 tumour (p = 0.049) and 70.0% and 89.1% in patients who showed no response to CRT (p = 0.039). The results suggest that a distal margin of less than 3 mm in the surgical specimen after preoperative CRT is associated with a lower rate of pelvic tumour control at five years in patients with stage ypT3-4 tumours or in those which do not respond to CRT. This article is protected by copyright. All rights reserved.
    Colorectal Disease 01/2014; · 2.08 Impact Factor
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    ABSTRACT: To investigate the prognostic role of the estrogen receptor (ER) in gastric cancer (GC) patients, tumor tissues from 932 patients with advanced GC were assessed for ER expression using immunohistochemistry, and their clinicopathologic features were evaluated. Forty patients (4.3%) had ER expression and they were more frequently associated with diffuse type gastric cancer and shorter disease free survival. Furthermore, we carried out in vitro analysis to evaluate the effect of ER modulation on the proliferation of GC cell lines. Estradiol enhanced proliferation of ER positive GC cells while it did not show any effect on ER negative GC cells. When ER was inhibited by fulvestrant and ER siRNA, estradiol-induced proliferation of ER positive GC cell was suppressed. Paclitaxel showed synergistic anti-proliferative impacts with fulvestrant. Suppressing ER by fulvestrant, paclitaxel and ER siRNA showed increased expression of E-cadherin, which is a crucial factor in diffuse-type carcinogenesis.
    Scientific reports. 01/2014; 4:7592.
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    ABSTRACT: Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N = 432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N = 186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N = 216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N = 300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N = 216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence = 3.16, p = 0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio = 1.77, p = 0.0053).
    PLoS ONE 01/2014; 9(3):e90133. · 3.53 Impact Factor
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    ABSTRACT: Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome sequencing of 49 GCs with diffuse (N=31) and intestinal (N=18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.
    Nature Communications 01/2014; 5:5477. · 10.74 Impact Factor
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    ABSTRACT: Background Trametinib, an oral mitogen/extracellular signal-related kinase (MEK)1/2 inhibitor, holds promise for malignancies with rat sarcoma (RAS) mutations, like pancreas cancer. This phase II study was designed to determine overall survival (OS) in patients with pancreas cancer treated with trametinib and gemcitabine. Secondary end-points included progression-free survival (PFS), overall response rate (ORR) and duration of response (DOR); safety end-points were also assessed. Methods Adults with untreated metastatic adenocarcinoma of the pancreas were randomised (1:1) to receive intravenous gemcitabine 1000 mg/m2 (weekly × 7 for 8 weeks, then days 1, 8 and 15 of 28-day cycles) plus trametinib or placebo 2 mg daily. RAS mutations were determined in circulating free DNA (cfDNA) and archival tumour tissue. OS was evaluated in kirsten rat sarcoma viral oncogene homolog (KRAS) mutant and wild-type subgroups. Results Baseline characteristics for 160 patients were similar in both treatment arms. There was no significant difference in OS (hazard ratio (HR) 0.98; 95% confidence interval (CI), 0.67–1.44; P = .453); median OS was 8.4 months with gemcitabine plus trametinib and 6.7 months with gemcitabine plus placebo. Median PFS (16 versus 15 weeks), ORR (22% versus 18%) and median DOR (23.9 versus 16.1 weeks) were also similar for trametinib and placebo arms, respectively. KRAS mutation-positive patients (n = 103) showed no difference in OS between arms. Thrombocytopenia, diarrhoea, rash and stomatitis were more frequent with trametinib, as was grade 3 anaemia. Conclusions The addition of trametinib to gemcitabine did not improve OS, PFS, ORR or DOR in patients with previously untreated metastatic pancreas cancer. Outcomes were independent of KRAS mutations determined by cfDNA.
    European Journal of Cancer. 01/2014;
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    ABSTRACT: Oncogenic mutational analysis provides predictive guidance for therapeutics such as anti-EGFR antibodies, but it is successful only for a subset of colorectal cancer (CRC) patients.
    PLoS ONE 01/2014; 9(8):e103551. · 3.53 Impact Factor

Publication Stats

2k Citations
513.24 Total Impact Points

Institutions

  • 2002–2014
    • Sungkyunkwan University
      • • School of Medicine
      • • Department of Surgery
      • • Samsung Medical Center
      Sŏul, Seoul, South Korea
    • Yonsei University
      • Department of Radiation Oncology
      Seoul, Seoul, South Korea
  • 2007–2013
    • Samsung Medical Center
      • Department of Hematology and Oncology
      Seoul, Seoul, South Korea
  • 2011
    • Dankook University Hospital
      Anjŏ, Gyeonggi Province, South Korea