No abstract available.
Esophagus* ; Melanoma*

We report herein a case of primary cutaneous diffuse large B-cell lymphoma with multiple skin lesions in a Korean woman. A 56-year-old woman presented with rapidly growing multiple sub-cutaneous nodules in her right flank and right upper arm. Microscopic examination of skin biopsy specimen showed diffuse infiltrates of large atypical lymphocytes with vesicular nuclei, prominent nucleoli and moderate degree of mitotic figures in deep dermis and subcutis. Immunophenotypic studies revealed the lymphoid infiltrates reacted with CD45, CD20 and bcl-2 protein, but none of the sections expressed CD3, bcl-6 protein and CD30. In physical examination and staging work-up, we could not find any other extracutaneous or systemic involvement. She was treated with 2 cycles of high-dose multiagent chemotherapy with the Vanderbilt and the BEAM regimen combined with the autologous peripheral blood stem cell transplantation. Until now, 10 months after termination of treatment, she has shown improvement of all skin lesions and no development of extracutaneous disease.
Arm ; B-Lymphocytes* ; Biopsy ; Dermis ; Drug Therapy ; Female ; Humans ; Lymphocytes ; Lymphoma, B-Cell* ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Physical Examination ; Skin

PURPOSE: As a new strategy to modulate drug resistance in the treatment of relapsed or refractory non-Hodgkin's lymphoma(NHL), continuos infusion of drugs has been incorporated into the chemotherapy. We conducted a phase II study to determine the activity and safety of EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisolone) chemotherapy, in which the natursl products are administered as a continuous infusion, for previously treated NHL's of intermediate grade. MATERIALS AND METHODS: EPOCH chemotherapy (etoposide 50 mg/m2/day 24 hour- continuous infusion, days 1~4, vincristine 0.4 mg/m2/day 24 hour-continuous infusion, days 1~4, doxorubicin 10 mg/m2/day 24 hour-continuous infusion, days 1~4, cyclophosphamide 750 mg/m2 i.v., day 5, prednisolone 60 mg/m2/day p.o. days 1-5) was given to eligible patients every 3 weeks and we assessed response and toxicity of the regimen. RESULTS: Between June 1993 and December 1995, total 56 patients entered this trial and 49 were evaluable. The complete response rate was 41%(95% C.I.: 27-55%). After follow up of 9~50(median 38) months, progression free survival was 0~39+(median 7) months and the overall survival was 1~44+(median 14) months. The prognostic factor analyses showed that B symtoms and serum LDH level before treatment and response to previous treatment affected complete response rate, and patients' performance status and response to previous treatment affected progression free survival and overall survival. Toxicities of EPOCH regimen were leukopenia, stomatitis, nausea/vomiting and neurotoxicity, but they were tolerable. There was 1 case of treatment-related death due to sepsis. CONDUSION: EPOCH chemotherapy was safe and effective for the patients with relapsed NHL. However, the results of patients with NHL refractory to previous treatment were so poor that more intensive, novel treatment would be needed for this category of patients.
Cyclophosphamide ; Disease-Free Survival ; Doxorubicin* ; Drug Resistance ; Drug Therapy* ; Follow-Up Studies ; Hodgkin Disease* ; Humans ; Leukopenia ; Lymphoma, Non-Hodgkin ; Prednisolone ; Sepsis ; Stomatitis ; Vincristine*

BACKGROUND: It has been reported that younger patients with lung cancer have characteristic features that differ from those in older patients. The prognosis for young patients with this disease is controversial. This study aimed to determine the clinicopathological characteristics, the survival rate, and the risk factors associated with the overall survival rate in younger patients with lung cancer. METHODS: The records of 120 young(age≤40) patients with histologically confirmed lug cancer in the Korea Cancer Center Hospital(KCCH) between Jan. 1992 to 1998, 120 older(age>40) patients were randomly selected as the controls. RESULTS: More female patients(45.0% vs. 20.0%, p<0.001) and more adenocarcinoma cases(64.2% vs. 38.3%, p<0.001) were found in the younger group, when compared to the older patients. In NSCLC, advanced disease(stage III B and IV) was more common in the younger patients(90.2%) than in the older patients(62.7%) (p<0.001). The Median survival was 8.6 months in the younger patients and 12.2 months in the older(p=0.003). In a multivariate analysis, only the advanced-stage was an independent negative prognostic factor. CONCLUSION: Lung cancer in the younger age group presents with a more advanced stage resulting in a poor survival rate, which suggests that lung cancer in this population is more aggressive than in older patients.
Adenocarcinoma ; Female ; Humans ; Korea ; Lung Neoplasms* ; Lung* ; Multivariate Analysis ; Prognosis ; Risk Factors ; Survival Rate

PURPOSE: The incidence of gastrointestinal stromal tumors (GISTs) harboring platelet-derived growth factor receptor alpha (PDGFRA) mutations is low, therefore further investigation of the efficacy of imatinib in this subgroup was needed. MATERIALS AND METHODS: Patients with PDGFRA-mutant GISTs who received imatinib as primary therapy for advanced disease between January 2000 and June 2012 were identified from the GIST registry of Asan Medical Center, Seoul, Korea. RESULTS: KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Exon 18 D842V substitution, non-D842V exon 18 mutations, and exon 12 mutations were detected in nine (50%), four (22%), and five (28%) patients, respectively. Objective response rate differed significantly between patients with the D842V mutation and those with non-D842V mutations (0% [0/5] vs. 71% [5/7], p=0.03). In all patients, median progression-free survival (PFS) and overall survival (OS) was 24.8 months (95% confidence interval [CI], 0.0 to 57.2) and 51.2 months (95% CI, 37.1 to 65.3), respectively. Significantly, poorer PFS was observed for patients with D842V-mutant GISTs than those with non-D842V PDGFRA-mutant GISTs: median 3.8 months (95% CI, 1.4 to 6.3) versus 29.5 months (95% CI, 18.3 to 40.7) (p < 0.001). Patients with the D842V mutation had poorer OS than those with non-D842V PDGFRA mutations: median 25.2 months (95% CI, 12.7 to 37.8) versus 59.8 months (95% CI, 43.0 to 76.5) (p=0.02). CONCLUSION: Imatinib is active against non-D842V PDGFRA-mutant GISTs, whereas GISTs harboring the D842V mutation are primarily resistant to imatinib.
Chungcheongnam-do ; Disease-Free Survival ; Exons ; Gastrointestinal Stromal Tumors ; Humans ; Incidence ; Korea ; Platelet-Derived Growth Factor* ; Receptors, Platelet-Derived Growth Factor* ; Seoul

PURPOSE: The cytotoxicity by 5-fluorouracil (5-FU) is mediated by inhibition of thymi- dylate synthase (TS), which is a rate-limiting enzyme for DNA synthesis. To test whether the resistance to 5-FU would be associated with cellular TS activity, we analyzed TS gene expression from human gastrointestinal cancer cell lines. MATERIALS AND METHODS: We established the experimental conditions for quantitating TS mRNA expression by competitive RT-PCR using mimic DNA. Based on this method, we compared TS mRNA expression between 5-FU resistant cell line and parent cell line and investigated the expression of TS mRNA following 5-FU administration in 6 human gas- trointestinal cancer cell lines. RESULTS: Competitive RT-PCR using mimic DNA seemed to be more effective than Northern blot analysis for quantitation of TS gene expression. The quantity of TS mRNA and IC50 value of 5-FU in 5-FU resistant H630 was found to be 2.5 and 10 times higher than in parent cell line, respectively. And also, we observed linear relationship between TS mRNA level and IC50 value of 5-FU (r 0.76) in 6 gastrointestinal cancer cell lines. CONCLUSION: These results suggest that overexpression of TS mRNA may play a role in the development of 5-FU resistance in human gastrointestinal malignancies
Blotting, Northern ; Cell Line ; DNA ; Drug Resistance* ; Fluorouracil* ; Gastrointestinal Neoplasms ; Gene Expression ; Humans* ; Inhibitory Concentration 50 ; Parents ; RNA, Messenger* ; Thymidylate Synthase*

No abstract available.
Small Cell Lung Carcinoma*

PURPOSE: Drug resistance is one of the major obstacles to treatment of cancer. Multidrug resistance (MDR) caused by overexpression of p-glycoprotein (Pgp) in cancer cell membrane is a well-known mechanism of drug resistance in in vitro system and was reported to be a significant mechanism of resistance in non-Hodgkins lymphoma (NHL). Verapamil, a calcium channel blocker, is proven in vitro to overcome the MDR caused by Pgp. We performed a phase II trial of verapamil in patients with NHL refractory to EPOCH regimen (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) to overcome the MDR caused by Pgp. MATERIALS AND METHODS: Verapamil was administered via intravenous route from 1 hour before to 12 hour after the 96-hour infusion of etoposide, doxorubicin, and vincristine which were known to be substrates of Pgp in EPOCH regimen. The dose of verapamil was 0.15 mg/Kg in bolus and 0.2 mg/Kg/hr in infusion at the beginning and escalated by 0.05 mg/Kg/hr every 24 hours if there was no dose-limiting toxicities such as 2nd or 3rd degree AV block, hypotension, or congestive heart failure. Plasma verapamil concentrations were measured every 24 hour by gas chromatography. Mdrl expression level in tumor tissues was measured by RT-PCR. RESULTS: From Feb. to Nov. 1994, 14 patients were treated with this protocoL However, poor tolerability and no response in these patients led to early closure of the study at this 1st stage of patient accrual according to Gehans method. Among 14 patients, 12 experienced 2nd or 3rd degree AV block and/or hypotension and required temporary cessation of infusion and reduction of verapamil dose. However, there was no congestive heart failure or treatment-related death. The peak concentrations of verapamil were 0.29-1.94 pM (mean 0.93 pM) and mean concentrations during the 4-day infusion were 0.22-1.21 pM (mean 0.6 pM). Mdrl expression levels measured in 6 patients were 0.99-14.43 U (median 4.39). CONCLUSION: These results suggest that verapamil in this dose and schedule was neither tolerable nor effective for the reversal of drug resistance in NHL patients.
Appointments and Schedules ; Atrioventricular Block ; Calcium Channels ; Cell Membrane ; Chromatography, Gas ; Cyclophosphamide ; Doxorubicin ; Drug Resistance* ; Drug Resistance, Multiple ; Etoposide ; Heart Failure ; Hodgkin Disease* ; Humans ; Hypotension ; Lymphoma, Non-Hodgkin ; P-Glycoprotein ; Plasma ; Prednisolone ; Verapamil* ; Vincristine

OBJECTIVE: The combination of vincristine and doxorubicin by continuous infusion was reported to reduce tumor mass more rapidly than standard regimens, which maybe a result of effect on more slowly proliferating plasma cells. We conducted a phase II study to determine the activity and safety of VAD (vincristine, doxorubicin, dexamethasone) chemotherapy, in which vincristine and doxorubicin are administered as a continuous infusion, for previously untreated multiple myeloma. METHODS: VAD chemotherapy (vincristine 0.4 mg/day 24 hour-continuous infusion, days 1~4; doxorubicin 9 mg/m2/day 24 hour-continuous infusion, days 1~4; dexamethasone 40 mg/day p.o. days 1~4) was given to eligible patients every 4 weeks and we assessed response and toxicity of the regimen. RESULTS: Between January 1991 and March 1997, total 25 patients entered this trial and 22 were evaluable. The complete response rate was 14%(3/22) and overall response rate was 59%(13/22, 95% C.I.: 38~80%). The time to response was 1.0~6.8(median 2.9) months. Progression free survival was 2~39+(median 11.5) months and the overall survival was 3+~42+(median 19.7) months. Toxicities of VAD regimen were leukopenia, infection, stomatitis and neurotoxicity, but there was no treatment-related death. CONCLUSION: VAD chemotherapy was tolerable, but not more active than the alkylating agent-based chemotherapy as a front-line treatment for the patients with multiple myeloma. But, because of its rapid response and relatively mild myelotoxicity, it could play a role for advanced or highly complicated disease and for remission induction before consolidation with high-dose chemotherapy.
Dexamethasone* ; Disease-Free Survival ; Doxorubicin* ; Drug Therapy* ; Humans ; Leukopenia ; Multiple Myeloma* ; Plasma Cells ; Remission Induction ; Stomatitis ; Vincristine*

BACKGROUNDS/AIMS: Vitamin K may plays a role in controlling hepatocellular carcinoma (HCC) cell growth. In this study, we intended to present 5-year experience of 72 patients receiving oral vitamin K with or without sorafenib. Its end-point was to evaluate the safety of combination therapy using sorafenib and vitamin K. METHODS: An interim analysis was performed as a single-arm cross-sectional study, including 72 HCC patients who underwent liver resection or transplantation and administered oral vitamin K2 alone (n=47) or with sorafenib (n=25). RESULTS: In all patients, administration of vitamin K2 analog 45 mg/day did not show any noticeable adverse side-effect during vitamin K therapy of 23.3+/-10.6 months, except for one patient who experienced skin rash at the third day of vitamin K therapy. In 25 patients receiving sorafenib and vitamin K for 6 months or longer, any noticeable adverse side-effect suspected of vitamin K origin was not identified yet. A small proportion of patients showed unexpectedly favorable anti-tumor effects after use of vitamin K with or without sorafenib. CONCLUSIONS: Because add-on of oral vitamin K did not increase the adverse side-effects of sorafenib, a combination therapy with these two agents appears to be worthy of further clinical trial with an expectation of synergistic therapeutic effects.
Carcinoma, Hepatocellular* ; Cross-Sectional Studies ; Exanthema ; Humans ; Liver ; Neoplasm Metastasis ; Vitamin K 2 ; Vitamin K*