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1.
Cancer Research and Treatment ; : 189-195, 2023.
Article in English | WPRIM | ID: wpr-966477

ABSTRACT

Purpose@#The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC). @*Materials and Methods@#Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity. @*Results@#Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin. @*Conclusion@#The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

2.
Journal of Liver Cancer ; : 350-361, 2023.
Article in English | WPRIM | ID: wpr-1001322

ABSTRACT

Background@#/Aim: Patients with large (>5 cm) hepatocellular carcinoma (HCC) have limited treatment options, thus necessitating the identification of prognostic factors and the development of predictive tools. This study aimed to identify prognostic factors and to construct a nomogram to predict survival outcomes in patients with large HCC. @*Methods@#A cohort of 438 patients, who were diagnosed with large HCC at a tertiary hospital between 2015 and 2018, was analyzed. Cox proportional hazards models were used to identify key prognosticators of overall survival (OS), and an independent set of prognostic factors was used to develop a nomogram. The discrimination and calibration abilities of the nomogram were assessed and internal validation was performed using cross-validation and bootstrapping methods. @*Results@#During a median follow-up of 9.3 months, the median OS was 9.9 months, and the 1-year OS rate was 43.9%. Multivariable Cox regression analysis revealed that performance status, modified albumin-bilirubin grade, tumor size, extent of portal vein tumor thrombosis, and initial treatment significantly affected OS. The newly developed nomogram incorporating these variables demonstrated favorable accuracy (Harrell’s concordance index, 0.807). @*Conclusions@#The newly developed nomogram facilitated the estimation of individual survival outcomes in patients with large HCC, providing an acceptable level of accuracy.

3.
Cancer Research and Treatment ; : 446-454, 2020.
Article | WPRIM | ID: wpr-831053

ABSTRACT

Purpose@#The purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levelsin improving the performance of magnetic resonance imaging (MRI) for the predictionof pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectalcancer. @*Materials and Methods@#We retrospectively reviewed the medical records of 524 rectal cancer patients who underwentNCRT and total mesorectal excision between January 2009 and December 2014. Theperformances of MRI with or without CEA parameters (initial CEA and CEA dynamics) forprediction of pathologic tumor response grade (pTRG) were compared by receiver-operatingcharacteristic analysis with DeLong’s method. Cox regression was used to identify the independentfactors associated to pTRG and disease-free survival (DFS) after NCRT. @*Results@#The median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis,poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) andthe mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed associationwith poor pTRG. The mrTRG plus CEA parameters showed significantly improved performancesin the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEAwere also identified as independent factors associated with DFS. The initial CEA further discriminatedDFS in the subgroups with good mrTRG or that without mrMFI. @*Conclusion@#The CEA parameters significantly improved the performance of MRI in the prediction ofpTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initialCEA level in the groups with favorable MRI parameters.

4.
Cancer Research and Treatment ; : 876-885, 2019.
Article in English | WPRIM | ID: wpr-763191

ABSTRACT

PURPOSE: The purpose of this study was to compare prognostic differentiation performances of the 7th and the 8th edition of American Joint Committee on Cancer (AJCC) staging system for gastric cancer (GC) patients. MATERIALS AND METHODS: A total of 1,633 GC patients who underwent curative D2 resection followed by adjuvant chemotherapy alone (CA) or concurrent chemo-radiotherapy (CCRT) from 2004 to 2013 were included. Concordance index (c-index) was applied to compare the discriminatory ability. RESULTS: In the 8th edition, migration of stage was detected in 248 patients (15.2%). Among them, 121 patients were up-staged while 127 patients were down-staged. Overall, there was no statistically significant difference in the discriminatory ability between the 7th and 8th editions. The new edition of staging system, however, showed a trend of better prognostic performance not only in recurrence-free survival (c-index=0.734; 95% confidence interval [CI], 0.706 to 0.762 in the 7th edition vs. c-index=0.740; 95% CI, 0.712 to 0.768 in the 8th edition; p=0.14), but also in overall survival (c-index=0.717; 95% CI, 0.688 to 0.745 in the 7th edition vs. c-index=0.722; 95% CI, 0.694 to 0.751 in the 8th edition; p=0.19), especially in stage III. This finding was repeated in the subgroup analysis regardless of adjuvant CA or CCRT. CONCLUSION: Generally, the 8th edition of AJCC staging system had failed to show a superior discriminatory ability for curatively D2 resected GC patients than the 7th edition, although there was a trend of better prognostic performance of the new edition, regardless of adjuvant treatment method.


Subject(s)
Humans , Chemotherapy, Adjuvant , Joints , Methods , Neoplasm Staging , Prognosis , Radiotherapy , Recurrence , Stomach Neoplasms
5.
Cancer Research and Treatment ; : 1128-1134, 2019.
Article in English | WPRIM | ID: wpr-763167

ABSTRACT

PURPOSE: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC). MATERIALS AND METHODS: Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m² plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m² twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation. CONCLUSION: Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.


Subject(s)
Humans , Apoptosis , Arm , Bevacizumab , Capecitabine , Cellular Senescence , Colorectal Neoplasms , Creatine Kinase , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Liver , Simvastatin , Tablets , Treatment Outcome
6.
Cancer Research and Treatment ; : 510-518, 2019.
Article in English | WPRIM | ID: wpr-763143

ABSTRACT

PURPOSE: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints. RESULTS: A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8). CONCLUSION: OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.


Subject(s)
Humans , Biomarkers , Carcinoma, Hepatocellular , Cohort Studies , Disease-Free Survival , Dizziness , Fatigue , Maximum Tolerated Dose , STAT3 Transcription Factor , Thrombocytopenia
7.
Cancer Research and Treatment ; : 488-494, 2018.
Article in English | WPRIM | ID: wpr-714224

ABSTRACT

PURPOSE: The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC. MATERIALS AND METHODS: Patients with locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4 weeks and tumor response was evaluated every two cycles. The primary objective was overall response rate (ORR). RESULTS: A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay. CONCLUSION: In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.


Subject(s)
Humans , Male , Carcinoma, Renal Cell , Disease-Free Survival , Korea , Prospective Studies , Vascular Endothelial Growth Factor A
8.
The Korean Journal of Internal Medicine ; : 383-390, 2018.
Article in English | WPRIM | ID: wpr-713534

ABSTRACT

BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. RESULTS: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.


Subject(s)
Female , Humans , Adenocarcinoma , Diagnosis , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Gynecology , Hematuria , Recurrence , Retrospective Studies , Urinary Bladder Neoplasms , Urinary Bladder
9.
Journal of Gastric Cancer ; : 348-355, 2018.
Article in English | WPRIM | ID: wpr-719162

ABSTRACT

PURPOSE: We aimed to discuss the roles of radiation and chemotherapy as adjuvant treatment in patients with staged IB GC who were enrolled in the adjuvant chemoradiotherapy in stomach tumors (ARTIST) trial. MATERIALS AND METHODS: Among the 458 patients who were enrolled in the ARTIST trial, 99 had stage IB disease. The patients were randomly assigned to receive either adjuvant chemoradiotherapy with capecitabine plus cisplatin (XP, n=50) or chemoradiotherapy (XPRT, n=49). Survival analyses were performed in accordance with the AJCC 2010 staging system. RESULTS: According to the AJCC 2010 system, stage migration from IB to II occurred in 71% of the patients; 98% of the T2 N0 cases were reclassified as T3 N0, and 42% of the T1 N1 cases were reclassified as T1 N2. When comparing survival outcomes between the XPRT and XP arms for stage IB cancer (AJCC 2002), no significant difference in 5-year disease-free survival (DFS) between the 2 arms was found. (median 5-year DFS, not reached, P=0.256). The patients classified as having stage IB cancer (AJCC 2002) and reclassified as having stage II cancer (AJCC 2010) exhibited worse prognoses than those who remained in stage IB, although the difference was not statistically significant (5-year DFS rate, 83% vs. 93%). When we compared 5-year DFS in 70 patients with stage II (AJCC 2010), the addition of radiotherapy to XP chemotherapy did not show better outcome than XP alone (P=0.137). CONCLUSIONS: The role of adjuvant chemoradiotherapy in the treatment of stage IB GC (AJCC 2002) warrants further investigation.


Subject(s)
Humans , Arm , Capecitabine , Chemoradiotherapy , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Cisplatin , Disease-Free Survival , Drug Therapy , Prognosis , Radiotherapy , Stomach Neoplasms , Stomach
10.
Journal of Gastric Cancer ; : 105-110, 2016.
Article in English | WPRIM | ID: wpr-108714

ABSTRACT

PURPOSE: In the Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial, we investigated whether chemoradiotherapy after D2 gastrectomy reduces the rate of recurrence. Recently, the ratio of metastatic lymph nodes to examined lymph nodes (N ratio) has been proposed as an independent prognostic factor in gastric cancer (GC). The aim of this study was to investigate the relationship between the metastatic N ratio and prognosis of GC after curative D2 surgery. MATERIALS AND METHODS: We retrospectively reviewed the data of 458 ARTIST patients who underwent D2 gastrectomy followed by adjuvant chemotherapy (XP, n=228) or chemoradiotherapy (XPRT, n=230). The disease-free survival (DFS) rates of patients were used to evaluate the influence of N ratio on the treatment outcome. To achieve this, 4 different N ratio categories (0%, 1%~9%, 10%~25%, and >25%) were compared on the basis of their influence on the treatment outcome. RESULTS: On multivariate analysis, the N ratio remained an independent prognostic factor for DFS. The hazard ratios (HRs) for the N ratio categories of 0%, 1%~9%, 10%~25%, and >25% were 1, 1.061, 1.202, and 3.571, respectively. In patients having N ratio >25%, the 5-year DFS rates were 55% and 28% for the XPRT and XP arms, respectively (HR, 0.527; 95% confidence interval, 0.307~0.904; P=0.020). CONCLUSIONS: In patients with curatively resected GC, the N ratio was independently associated with DFS. Although this finding warrants further investigation in future prospective studies, the benefit of chemoradiotherapy for D2 resected GC appears to be more beneficial in cancers having N ratios >25%.


Subject(s)
Humans , Arm , Chemoradiotherapy , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Disease-Free Survival , Gastrectomy , Lymph Nodes , Multivariate Analysis , Prognosis , Prospective Studies , Recurrence , Retrospective Studies , Stomach Neoplasms , Stomach , Treatment Outcome
11.
Cancer Research and Treatment ; : 1243-1252, 2016.
Article in English | WPRIM | ID: wpr-109752

ABSTRACT

PURPOSE: The purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study). MATERIALS AND METHODS: Between January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients. RESULTS: More patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients. CONCLUSION: Sorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).


Subject(s)
Humans , Carcinoma, Hepatocellular , Diarrhea , Incidence , Korea , Life Change Events , Prospective Studies , Skin
12.
Radiation Oncology Journal ; : 34-44, 2016.
Article in English | WPRIM | ID: wpr-44797

ABSTRACT

PURPOSE: A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. MATERIALS AND METHODS: Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. RESULTS: A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. CONCLUSION: Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.


Subject(s)
Humans , Colorectal Neoplasms , Disease Progression , Fever , Follow-Up Studies , Hyperthermia, Induced , Liver , Neoplasm Metastasis , Prospective Studies , Quality of Life , Radiotherapy , Respiratory Insufficiency
13.
Cancer Research and Treatment ; : 553-560, 2016.
Article in English | WPRIM | ID: wpr-72541

ABSTRACT

PURPOSE: While the Trastuzumab for Gastric Cancer (ToGA) trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2-positive metastatic gastric cancer, the overall survival (OS) benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy. MATERIALS AND METHODS: Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively. RESULTS: A total of 168 Asian patients were included. The median age was 60 years (range, 27 to 85 years) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly-differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI], 8.7 to 11.7), and the median OS was 18.5 months (95% CI, 16.4 to 50.6). Next, we investigated the effect of poorly-differentiated histology (PDH, poorly-differentiated tubular adenocarcinoma+signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p=0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p=0.025). CONCLUSION: While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2-positive gastric cancer.


Subject(s)
Humans , Adenocarcinoma , Asian People , Carcinoma, Signet Ring Cell , Disease-Free Survival , Drug Therapy , Ethnicity , Receptor, ErbB-2 , Retrospective Studies , Stomach Neoplasms
14.
Cancer Research and Treatment ; : 72-77, 2015.
Article in English | WPRIM | ID: wpr-20374

ABSTRACT

PURPOSE: 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. MATERIALS AND METHODS: Chemotherapy-naive AGC patients were treated with capecitabine (1,000 mg/m2/day on days 1-14) plus cisplatin (75 mg/m2 on day 1), with or without epirubicin (50 mg/m2 on day 1). Complete blood counts including MCV were measured at baseline and on day 1 of each 3-week chemotherapy course. Macrocytosis was defined as a MCV increase > 10 fL from baseline. Multivariate Cox proportional hazards models were used for analysis of the impact of clinical and MCV values on chemotherapy outcomes. RESULTS: At baseline, the mean MCV was 88.2 fL (normal range, 80 to 100 fL). During chemotherapy, MCV increased in a dose-dependent manner with a mean increase of 11.3 fL. MCV elevation after capecitabine treatment in 74 patients (90%) and 44 patients (42%) developed macrocytosis. RESULTS: of multivariate analysis showed that development of macrocytosis was independent of baseline hemoglobin level, liver metastasis, performance status, or liver function. The number of chemotherapy cycles showed strong association with development of macrocytosis and hematologic adverse events. In addition, a significant association was observed between macrocytosis and clinical response or survival. CONCLUSION: Macrocytosis developed with more frequent and prolonged use of capecitabine. It is possible that association with treatment outcomes warrants further investigation.


Subject(s)
Humans , Blood Cell Count , Cisplatin , Drug Therapy , Epirubicin , Erythrocyte Indices , Incidence , Liver , Multivariate Analysis , Neoplasm Metastasis , Proportional Hazards Models , Stomach Neoplasms
15.
Cancer Research and Treatment ; : 343-361, 2015.
Article in English | WPRIM | ID: wpr-118314

ABSTRACT

Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin.


Subject(s)
Humans , Appointments and Schedules , Biliary Tract Neoplasms , Cholangiocarcinoma , Cisplatin , Congresses as Topic , Drug Therapy , Gallbladder Neoplasms , Incidence , Population Characteristics
16.
Cancer Research and Treatment ; : 141-147, 2014.
Article in English | WPRIM | ID: wpr-106248

ABSTRACT

PURPOSE: Collecting duct carcinoma (CDC) of the kidney is an aggressive disease with a poor prognosis, accountings for less than 1% of all renal cancers. To date, no standard therapy for CDC has been established. The aim of this study is an investigation of clinicopathologic findings of CDC and correlation of the disease status with a prognosis. MATERIALS AND METHODS: From 1996 to 2009, 35 patients with CDC were treated at eight medical centers. The diagnosis of CDC was made based on nephrectomy in 27 cases and renal biopsy in eight cases. RESULTS: Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4 months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was 8.6 months (95% CI 0 to 23.3), which showed a statistically significant difference (p=0.01). In addition, among patients with Stage IV, the OS of patients who received a palliative treatment (immunotherapy, chemotherapy, or targeted therapy) was 18.4 months, which was higher than the OS of patients without treatment of 4.5 months. CONCLUSION: CDC is a highly aggressive form of renal cell carcinoma. Despite most of the treatments, PFS and OS were short, however, there were some long-term survivors, therefore, conduct of additional research on the predictive markers of the several clinical, pathological differences and their treatments will be necessary.


Subject(s)
Humans , Biopsy , Carcinoma, Renal Cell , Diagnosis , Drug Therapy , Gynecology , Kidney , Kidney Neoplasms , Nephrectomy , Palliative Care , Prognosis , Survivors
17.
Yonsei Medical Journal ; : 883-887, 2013.
Article in English | WPRIM | ID: wpr-99050

ABSTRACT

PURPOSE: Phosphatidylinositol 3-kinases/AKT pathway plays a pivotal role in hepatocellular carcinoma (HCC). Mutant PIK3CA, encoding the p110a catalytic subunit, stimulates the AKT pathway and promotes cell growth in various cancers. PIK3CA mutation rate has been usually reported as low frequency (<5%) in HCC except one report from Korea with 35.6%. Therefore, we investigated the frequency of PIK3CA mutations in Korean HCC patients. MATERIALS AND METHODS: We sequenced exons1, 3, 4, 6, 7, 8, 9, 19 and 20 of PIK3CA in 268 HCC tumor tissue samples by Sanger method and pyrosequencing assay. RESULTS: In this study, the mutations were not detected in exons3, 6, 8, and 19, and detected 1 at unknown SNP in exon1 and exon4, 2 at unknown SNP in exon7, 2 at unknown SNP in exon20. However, 1 at unknown SNP, 1 at G1635T and surprisingly all samples at A1634Cin exon9 were detected by Sanger method. Additional experiments with normal tissue, cloning experiments and a pyrosequencing assay revealed that the double peak at A1634C of exon9 is a pseudogene, not true mutation. The mutations found in this study were all different and small numbers, therefore, we cannot conclude specific relationship between clinical characteristics of HCC and mutation of PIK3CA. CONCLUSION: Our study suggests that the rate of PIK3CA mutation in the Korea population is in fact similar to the rates seen elsewhere in the world.


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Asian People/genetics , Carcinoma, Hepatocellular/genetics , Exons , Liver Neoplasms/genetics , Mutation , Mutation Rate , Phosphatidylinositol 3-Kinases/genetics , Polymorphism, Single Nucleotide , Republic of Korea
18.
Radiation Oncology Journal ; : 171-174, 2013.
Article in English | WPRIM | ID: wpr-116460

ABSTRACT

Sorafenib is a multi-targeted kinase inhibitor, which is the current standard treatment for advanced hepatocellular carcinoma (HCC). Only one case of radiation recall dermatitis (RRD) associated with sorafenib has been reported so far. Our patient with recurrent HCC was treated with palliative radiotherapy (RT) for the chest wall mass. Sorafenib at 400 mg twice daily was begun on the day following RT. On the 14th day post-RT, an erythematous patch was observed on right chest wall which matched area previously irradiated. It was consistent with RRD. Ten days later, a disseminated exanthematous rash and severe pruritus occurred. Sorafenib was stopped and an oral antihistamine was prescribed to relieve symptoms. At the 1-week follow-up after the cessation of sorafenib, all symptoms were resolved. Physicians should be alert to this recall phenomenon as it can occur both in the skin and elsewhere and the occurrence of RRD may be unpredictable.


Subject(s)
Humans , Carcinoma, Hepatocellular , Exanthema , Follow-Up Studies , Niacinamide , Phenylurea Compounds , Phosphotransferases , Pruritus , Radiodermatitis , Skin , Thoracic Wall
19.
Cancer Research and Treatment ; : 96-101, 2011.
Article in English | WPRIM | ID: wpr-78355

ABSTRACT

PURPOSE: Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, has demonstrated efficacy and tolerability in treatment of advanced colorectal cancer (ACC). MATERIALS AND METHODS: Between January 2006 and December 2007, a total of 478 ACC patients were treated with combination chemotherapy in first-line settings. Combination therapies included: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until occurrence of disease progression or unacceptable toxicity, or until a patient chose to discontinue treatment. RESULTS: The median age was 58 years (range, 19 to 84 years) and the median chemotherapy durations for FOLFOX, FOLFIRI, XELOX, and XELIRI were 4.9, 4.5, 5.7, and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median progression-free-survival (PFS) for all patients was 6.8 months (95% confidence interval, 6.3 to 7.3 months). No statistically significant difference in PFS was found among regimens used as first-line chemotherapy. Sixty percent (n=290) of patients received second or further lines of therapy after failure. CONCLUSION: Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Camptothecin , Colonic Neoplasms , Colorectal Neoplasms , Deoxycytidine , Disease Progression , Drug Therapy, Combination , Fluorouracil , Leucovorin , Organoplatinum Compounds , Retrospective Studies
20.
Journal of Korean Medical Science ; : 1563-1568, 2011.
Article in English | WPRIM | ID: wpr-227749

ABSTRACT

Epidermal growth factor receptor (EGFR)-targeted therapies have been effective in some cancers, but not in hepatocellular carcinoma (HCC). The aim of this study was to investigate the drug potential to overcome multi-drug resistance in HCC cells. Thirteen drug-sensitive HCC cells were assessed using the CCK-8 assay. G0-G1 arrest was measured by FACS. Western blot analysis was used to detect the key enzymes in both the Ras/Raf and PI3K pathways. When establishing the IC50 of HCC to several drugs, including EKB-569, sorafenib, erlotinib, gefitinib, pazopanib, and brivanib, SK-Hep1 cells treated with EKB-569 have shown the highest (72.8%-86.4%) G0-G1 arrest and decreased the phosphorylation of AKT and ERK at the protein level. We found that EKB-569 had higher efficacy in HCC, compared to first generation, reversible EGFR-TK inhibitors. Furthermore, the combination of sorafenib and EKB-569 showed a synergistic effect to inhibit proliferation of SNU-475, previously the most resistant cell to EGFR-TKIs. Therefore, novel EKB-569 in combination with sorafenib may be able to overcome HCC resistance to EGFR-TK inhibitors.


Subject(s)
Humans , Aminoquinolines/pharmacology , Aniline Compounds/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Benzenesulfonates/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Drug Synergism , Liver Neoplasms/drug therapy , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Pyridines/pharmacology , ErbB Receptors/antagonists & inhibitors
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