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*

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

Coronary neovascularity may be formed in patients with the left atrial thrombus, and coronary artery disease may be associated with valvular heart disease. From August 1989 through September 1990, 109 patients over 40 years old with valvular heart disease were performed coronary arteriogram to evaluate the incidence of the associated coronary artery disease. And 9 patients with left atrial thrombi detected noninvasively were also performed coronary arteriogram to evaluate the significance of the neovascularity to predict the left atrial thrombus. The results were as follows : 1) Significant coronary arterial lesion(greater than 50% narrowing of the luminal diameter) was noted in three of 109 patients over 40 years old(2.8%), but there was no typical chest pain in all of the three patients. 2) The coronary neovascularity was found in 19 of 118 patients -18 with mitral valvular disease and one with combined valvular disease. All of the patients with the coronary neovascularity had established atrial fibrillataion and the neovasculaity was originated from the left circumflex artery in all of them. 3) Prosthetic valve replacement was performed in 42 of 118 patients during the study period and left atrial thrombus was found in ten patients with mitral valve disease. Neovascularity on coronary arteriogram was detected in six patients(sensitivity 60%) of the above 10 patiets, and 28 patients without neovascularity had no left atrial thrombus (28/32, specificity 87.5%). Our observation revealed that neovascularity might represent the left atrial thrombus in valvular heart disease, and the incidence of the associated coronary artery disease in valvular heart disease was very low(2.8%) in Korea. Coronary arteriography as a routine preoperative evaluation might be unnecessary in valvular heart disease in Korea.
Adult ; Angiography ; Arteries ; Chest Pain ; Coronary Artery Disease ; Heart Valve Diseases* ; Humans ; Incidence ; Korea ; Mitral Valve ; Phenobarbital ; Sensitivity and Specificity ; Thrombosis

Neuroendocrine tumors (NETs) are a group of malignancies arising from neuroendocrine cells and frequently originate in the gastrointestinal tract and pancreas. Although curative resection is the main treatment for localized disease, systemic therapy is needed for relapsed or metastatic/unresectable gastroenteropancreatic NETs (GEP-NETs). Although there are several NET treatment guidelines from various countries, the geographical discrepancies between patient clinical characteristics, the regulatory approval status for therapeutic agents, and medical practices necessitate specific guidelines for Korean patients. We here provide a consensus review of the diagnosis, staging and systemic treatment of Korean GEP-NET patients. Systemic therapy options and the current Korean expert consensus on these treatments, including somatostatin analogs, targeted therapies such as everolimus and sunitinib, peptide receptor radionuclide treatments, and cytotoxic chemotherapies are addressed.

Neuroendocrine tumors (NETs) are a group of malignancies arising from neuroendocrine cells and frequently originate in the gastrointestinal tract and pancreas. Although curative resection is the main treatment for localized disease, systemic therapy is needed for relapsed or metastatic/unresectable gastroenteropancreatic NETs (GEP-NETs). Although there are several NET treatment guidelines from various countries, the geographical discrepancies between patient clinical characteristics, the regulatory approval status for therapeutic agents, and medical practices necessitate specific guidelines for Korean patients. We here provide a consensus review of the diagnosis, staging and systemic treatment of Korean GEP-NET patients. Systemic therapy options and the current Korean expert consensus on these treatments, including somatostatin analogs, targeted therapies such as everolimus and sunitinib, peptide receptor radionuclide treatments, and cytotoxic chemotherapies are addressed.

Placement of the self-expandable metallic stents for palliative treatment of malignant esophagogastric strictures has been thought to be easy, fast and effective method than conventional methods (bypass procedures, radiation therapy, laser treatment, esophageal intubation, etc.). The expandable metallic stent tubes were found to overcome some of the limitations of nonexpandable conventional tubes. Their implantation is better tolerated and safer than that of nonexpandable tubes, because the risks of migration and perforation are lower.On our knowledge, there has been no report of pyloric obstruction after this metallic stent insertion.We hereby report a case of pyloric obstruction caused by a migrated self-expandable metallic stent for palliative treatment of malignant esophageal stricture.
Constriction, Pathologic ; Deglutition Disorders* ; Esophageal Neoplasms ; Esophageal Stenosis ; Intubation ; Laser Therapy ; Palliative Care ; Stents*

Multiple primary malignant neoplasms (MPMN) are defined by the presence of multiple primary cancers of multicentric origin and/or different tissues. The incidence of MPMN is less than 1% in Korea and recently seems to be increased due to early detection of cancer and prolonged survival of cancer patients. Previous investigations suggest that non-Hodgkin's lymphoma (NHL) may be associated with chronic liver disease and hepatocellular carcinoma (HCC). The pathogenesis of this association is thought to be due to chronic antigenic stimulation, the presence of HBsAg, and immunosuppressive therapy. We report a case of synchronous NHL and HCC in a 54-year-old man which is thought to be associated with hepatitis B virus infection. Pathological examination and immunohistochemical study of neck lymph node and liver mass biopsies showed diffuse large cell lymphoma and HCC, respectively. He was treated initially with EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide and prednisolone) chemotherapy for NHL and transarterial chemoembolization with doxorubicin, mitomycin-c, lipiodol, and gelfoam for HCC.
Biopsy ; Carcinoma, Hepatocellular* ; Cyclophosphamide ; Doxorubicin ; Drug Therapy ; Early Detection of Cancer ; Ethiodized Oil ; Gelatin Sponge, Absorbable ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Incidence ; Korea ; Liver ; Liver Diseases ; Lymph Nodes ; Lymphoma, Large B-Cell, Diffuse ; Lymphoma, Non-Hodgkin* ; Middle Aged ; Mitomycin ; Neck ; Vincristine

PURPOSE: The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients. MATERIALS AND METHODS: Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on/1 week off). RESULTS: None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a hand-foot skin reaction (n=31). CONCLUSION: This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.
Appointments and Schedules ; Disease-Free Survival ; Follow-Up Studies ; Gastrointestinal Stromal Tumors* ; Humans ; Imatinib Mesylate* ; Skin

PURPOSE: To determine treatment protocol for inoperable esophageal cancer patients, we evaluated survival rate and prognostic factors. MATERIALS AND METHODS: We evaluated esophageal cancer treated by curative or palliative aim in KCCH from 1992 to 1996, retrospectively. Recurrent or underdose case below 40 Gy were excluded. The number of male and female were 35 and 5, respectively. Thirty-eight patients were squamous carcinoma and 2 patients were not biopsy proven. Ten patients were treated with radiation therapy and chemotherapy. Median dose of radiation therapy was 59.4 Gy and the range was 40-60 Gy. RESULTS:The median survival is 6.5 months and 1-year survival rate was 28.3%. Age, location, radiation dose and chemotherapy were not significant prognostic factors. Median survivals of patients with below stage III and over stage IVA were 7.6 and 6.2 months respectively, but it is not significant. CONCLUSION:The survival for esophageal cancer is very poor. For patients with curative aim, chemotherapy must be considered. For patients with palliative aim, short-term external beam radiation therapy and/or brachytherapy must be considered.
Biopsy ; Brachytherapy ; Carcinoma, Squamous Cell ; Clinical Protocols ; Drug Therapy ; Esophageal Neoplasms ; Female ; Humans ; Male ; Retrospective Studies ; Survival Rate

BACKGROUND: Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC), however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, arid survival of concurrent chemotherapy with etoposide and cisplatin(EP) arid radiation therapy for unresectable stage III NSCLC. METHODS: Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without, malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide arid cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. RESULTS: Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient The median survival was l2.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia(> or = grade 3,46%) Thrombocytopenia over grade 3 was found in 1%. Radiation pneumonitis occurred in 13 patients(46%). CONCLUSION: Concurrent chemotherapy(EP) pins radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Drug Therapy* ; Etoposide* ; Humans ; Lung Neoplasms ; Pleural Effusion, Malignant ; Radiation Pneumonitis ; Radiotherapy ; Survival Rate ; Thorax ; Thrombocytopenia