Search

The role of non-surgical treatments (NS), such as chemoradiotherapy or radiotherapy, for clinical T1N0M0 esophageal cancer (cT1N0M0 EC) has not been well delineated. The aim of this study was to evaluate and compare the feasibility and efficacy of NS and Surgical treatment (S) in cT1N0M0 EC patients.The medical records of patients who received treatment for cT1N0M0 EC at Asan Medical Center between 2003 and 2012 were retrospectively reviewed. The baseline characteristics, treatment outcomes and complications, and survival were compared.There were 264 S and 20 NS patients with respective median ages of 69.5 and 63.0. The main histologic finding was squamous cell carcinoma in both groups (97 and 100 %, respectively). The Eastern Cooperative Oncology Group performance status and Charlson comorbidity index score were poorer in the NS group. With a median follow-up of 49.0 months, 37 S patients (14 %) and 3 NS patients (15 %) exhibited recurrence. The first sites of recurrence for S and NS patients were locoregional (21 vs. 3 patients), distant (6 vs. 0), and both locoregional and distant (9 vs. 0), respectively. The median time-to-recurrence could not be calculated in either group (log-rank test P = 0.831). The estimated median overall survival was 64.4 months (95 % CI 37.2-91.6 months) in the NS group and could not be calculated in the S group (P = 0.056).Non-surgical treatments can be an effective alternative to S for patients with cT1N0M0 EC unfit for radical surgery. The role of NS for early stage EC needs to be further verified with prospective randomized trials.

PURPOSE: Hypoxia-inducible factor-1 (HIF-1) facilitates the adaptation of normal and tumor tissues to oxygen deprivation. HIF-1 is frequently overexpressed in cancer cells, where it is involved in the upregulation of many genes necessary for survival. EZN-2968 is an antisense oligodeoxynucleotide that specifically targets HIF-1α, one of the subunits of HIF-1. We conducted a trial of EZN-2968 in patients with refractory solid tumors to evaluate antitumor response and to measure modulation of HIF-1α mRNA and protein levels as well as HIF-1 target genes. METHODS: Adult patients with refractory advanced solid tumors were administered EZN-2968 as a 2-h IV infusion at a dose of 18 mg/kg once a week for three consecutive weeks followed by 3-week off; in a 6-week cycle. Tumor biopsies and dynamic contrast enhanced MRI (DCE-MRI) were performed at baseline and after the third dose. RESULTS: Ten patients were enrolled, of whom all were evaluable for response; one patient with a duodenal neuroendocrine tumor had prolonged stabilization of disease (24 weeks). Reduction in HIF-1α mRNA levels compared to baseline was demonstrated in 4 of 6 patients with paired tumor biopsies. Reductions in levels of HIF-1α protein and mRNA levels of some target genes were observed in two patients. Quantitative analysis of DCE-MRI from two patients revealed changes in K(trans) and k(ep). The trial was closed prematurely when the sponsor suspended development of this agent. CONCLUSION: This trial provides preliminary proof of concept for modulation of HIF-1α mRNA and protein expression and target genes in tumor biopsies following the administration of EZN-2968.

To evaluate the efficacy and safety of 2-year adjuvant imatinib for patients at high risk of recurrence after complete resection of localized gastrointestinal stromal tumor with KIT exon 11 mutation.Imatinib 400 mg/d was administered until disease recurrence, intolerable toxicities, or for 2 years. The primary end point was recurrence-free survival.Patients (n = 47) from 4 centers in Korea were enrolled. Treatment was well tolerated. Grade 3-4 toxicities included neutropenia (27.7%), skin rash (8.5%), anorexia (4.3%), and constipation (2.1%). At a median follow-up of 56.7 months, 19 patients had recurrences. Median recurrence-free survival was 58.9 months, which was significantly longer than 22.7 months from historical data of 27 patients in the pre-imatinib era (P0.0001). Imatinib was rechallenged for 15 patients with recurrence after completion of adjuvant imatinib. Thirteen patients had partial response, and two had stable disease. There was only one death so far.Postoperative adjuvant imatinib for 2 years was safe and could prolong the recurrence-free survival in patients with a high risk of recurrence after complete resection of localized KIT exon 11 mutated gastrointestinal stromal tumor. Reintroduction of imatinib after recurrence appears to be effective if the recurrence develops after completion of adjuvant imatinib.

Although gastric cancer with isolated para-aortic lymph node (PAN) involvement is considered an advanced disease, the clinical characteristics of it have not been comprehensively elucidated.We reviewed the medical records of 1,277 patients received palliative chemotherapy with advanced gastric cancer according to metastatic sites: PAN-only metastasis, single organ metastasis other than PAN, and multiple organ metastasis. Time to other organ metastasis (TTOM) was determined only in PAN-only metastasis group as the time interval between initial diagnosis of recurrence or de novo metastasis and confirming distant metastasis beyond PAN area.The median overall survival (OS) of patients with PAN-only metastasis was significantly longer than that of patients with single organ metastasis other than PAN or multiple organ metastasis (13.8 months vs. 11.4 months vs. 8.4 months; P0.001). In the PAN-only metastasis group, patients with recurrent diseases showed longer TTOM beyond the PAN area (10.7 vs. 7.7 months; P = 0.037) and OS (23.8 vs. 12.8 months; P = 0.010) than those with de novo metastatic disease and it was validated by multivariate analysis.Patients with isolated PAN metastasis showed an excellent prognosis compared with patients with metastasis at other sites and it was primarily evident in patients with recurrent PAN metastasis.

Pemetrexed is a multitargeted antifolate enzyme inhibitor, which has activity against a variety of tumors, including advanced gastric cancer (AGC). The aim of this study was to assess efficacy and safety of pemetrexed plus cisplatin (PemCis) combination in the treatment of AGC in Korean patients.This was a multicenter, single arm, open label study. Patients with no prior palliative chemotherapy received pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) day 1, every 3 weeks plus folic acid and vitamin B(12) supplementation. Response rate was assessed according to response evaluation criteria in solid tumors (RECIST) criteria.Of the 50 patients evaluable for efficacy, 13 had partial response for an overall response rate of 26% (95% CI, 14.6-40.3%) and 15 (30%) had stable disease. Median time to progression was 2.8 months (95%CI, 2.2-4.4 months), and median overall survival was 6.6 months (95% CI, 4.8-10.4 months). Of the 51 patients evaluable for safety, the most frequent NCI-CTC grade 3/4 toxicities were neutropenia in 49% of patients (25% of cycles) and anorexia in 10% of patients (4% of cycles).PemCis has a modest activity and acceptable toxicity profile in patients with AGC. Clinical trials with different combinations and dose regimens are, therefore, warranted.

We conducted a phase I study of S-1 combined with irinotecan and oxaliplatin (TIROX) to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety, pharmacokinetics, pharmacogenetics, and preliminary efficacy in patients with metastatic colorectal cancer (MCRC) or metastatic gastric cancer (MGC).Patients received escalating doses of S-1 (30-40 mg/m² b.i.d.) orally on days 1-14, an escalating dose of intravenous irinotecan (120-150 mg/m²) on day 1, and a fixed dose of intravenous oxaliplatin (85 mg/m²) on day 1 every 3 weeks.Twenty-three patients (10 MCRC, 13 MGC; 13 chemonaive, 10 previously treated for metastatic disease) were treated across six dose levels. Because only one patient experienced a dose-limiting toxicity of grade 3 anorexia at the highest dose level (S-1 40 mg/m² b.i.d., irinotecan 150 mg/m², and oxaliplatin 85 mg/m²) (n = 8), the MTD was not obtained, and this level was established as the RD. With a median of 10 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (43 %), diarrhea (13 %), and nausea (13 %). In 22 efficacy-evaluable patients, the objective tumor response rate was 59.1 % (75 % for both MCRC and MGC in the first-line setting) and the disease control rate was 100 %. The exploratory pharmacokinetic/pharmacogenetic study showed that CYP2A6 variants (*4, *7, *9) are associated with a lower metabolic ratio of S-1 (exposure ratio of 5-fluorouracil to tegafur).The new triplet TIROX regimen has shown promising antitumor activity and a favorable toxicity profile in patients with MCRC and MGC.

We performed a retrospective study to evaluate the efficacy of cetuximab plus chemotherapy in metastatic gastric cancer (MGC) patients previously treated with chemotherapy and to investigate potential predictors of treatment efficacy in those patients. Thirty-two patients with MGC were included in this study. Cetuximab was delivered, often combined with irinotecan-based chemotherapy. Thirty patients were analyzed for K-ras mutations via direct sequencing of the tumor DNA. Patients were heavily pretreated with a median number of three previous lines of palliative chemotherapy (56% of the patients were refractory to all of the following drugs: fluoropyrimidines, cisplatin, irinotecan, oxaliplatin, and docetaxel) and 53% of the patients displayed poor performance status. Of 28 response-assessable patients, the overall response rate to cetuximab plus chemotherapy was 3.6% [95% confidence interval (CI) 0–10.5%] and the disease control rate was 28.6%. The median progression-free survival (PFS) was 1.7 months (95% CI 1.3–2.1 months), and the median overall survival (OS) was 3.2 months (95% CI 1.4–5.0 months). Multivariate analyses revealed that skin rash and performance status were significantly associated with PFS and OS. The presence of a K-ras mutation (13.3%) was not associated with either PFS or OS. Our study suggests that MGC patients with good performance status and skin rash benefit most from salvage cetuximab combined with chemotherapy, even in heavily pretreated status.