Cancer Research and Treatment

Original Articles

An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer: In Hae Park, Joo Hyuk Sohn, Sung Bae Kim, Keun Seok Lee, Joo Seop Chung, Soo Hyeon Lee, Tae You Kim, Kyung Hae Jung, Eun Kyung Cho, Yang Soo Kim, Hong Suk Song, Jae Hong Seo, Hun Mo Ryoo, Sun Ah Lee, So Young Yoon, Chul Soo Kim, Yong Tai Kim, Si Young Kim, Mi Ryung Jin, Jungsil Ro; Cancer Res Treat. 2017;49(3):569-577. Published online September 12, 2016; DOI: https://doi.org/10.4143/crt.2016.289

Purpose
Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol).
Materials and Methods
Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR).
Results
The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p_{non-inferiority}=0.021, p_superiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments.
Conclusion
Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Citations

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Acta Pharmacologica Sinica.2017; 38(6): 931. CrossRef

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Efficacy of Low-dose Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer: Byung Su Kim, Do Youn Oh, Yo Han Joh, Do Yeun Kim, Jee Hyun Kim, Se Hoon Lee, Dae Ho Lee, Tae You Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; Cancer Res Treat. 2001;33(6):469-473. Published online December 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.6.469

Abstract PDF

PURPOSE
To evaluate the efficacy and toxicity of combination chemotherapy with low-dose paclitaxel and cisplatin in patients with advanced non-small cell lung cancer.
MATERIALS AND METHODS
Chemotherapy-naive patients with unresectable, pathologically proven non-small cell lung cancer were eligible for inclusion in the study. Patients received paclitaxel (145 mg/m2 iv 3 hour D1) and cisplatin (60 mg/m2 iv D1) every 3 weeks.
RESULTS
Forty-two patients were enrolled between February 2000 and February 2001. The median age was 53.5 years. Patients with adenocarcinoma numbered 29, squamous cell carcinoma 7, large cell carcinoma 3, and undifferentiated carcinoma 3. Seventeen patients had stage IIIB, 19 had stage IV disease and the remaining 6 displayed recurred disease after previous surgical resection. Four patients terminated treatment early because of hypersensitivity (1) and severe emesis (3). Of the 38 evaluable patients, 14 had PR and the response rate was 36.8%. Among partial responders, 6 patients received additional chest radiation. The median duration of response was 47.9 weeks and the median overall survival was 54.0 weeks. Of the total 176 courses, 14 were delayed, 22 required dose reduction, and grade 3~4 neutropenia occurred in 5.6% of courses. Only one episode of neutropenic fever developed and there were no treatment- related mortalities. Other toxicities were generally mild.
CONCLUSION
The combination chemotherapy with low-dose paclitaxel and cisplatin was effective and tolerable in patients with advanced non-small cell lung cancer.

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Phase II Study of Low-dose Paclitaxel and Cisplatin as a Second-line Therapy after 5-Fluorouracil/Platinum Chemotherapy in Gastric Cancer
Keun-Wook Lee, Jee Hyun Kim, Tak Yun, Eun Kee Song, Im il Na, Hyunchoon Shin, So Yeon Oh, In Sil Choi, Do-Youn Oh, Dong-Wan Kim, Seock-Ah Im, Tae-You Kim, Jong Seok Lee, Dae Seog Heo, Yung-Jue Bang, Noe Kyeong Kim
Journal of Korean Medical Science.2007; 22(Suppl): S115. CrossRef
Phase II Trial of Low-dose Paclitaxel and Cisplatin in Patients with Advanced Gastric Cancer
Keun-Wook Lee, Seock-Ah Im, Tak Yun, Eun Kee Song, Im il Na, Hyunchoon Shin, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Dong-Wan Kim, Tae-You Kim, Jong Seok Lee, Dae Seog Heo, Yung-Jue Bang, Noe Kyeong Kim
Japanese Journal of Clinical Oncology.2005; 35(12): 720. CrossRef

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Phase II Trial of Vinorelbine and Cisplatin Chemotherapy in Advanced Non-Small Cell Lung Cancer: Yo Han Joh, Tae You Kim, Im Il Na, Do Youn Oh, Byung Su Kim, Jee Hyun Kim, Do Yeun Kim, Se Hoon Lee, Chul Gyu Yoo, Choon Taek Lee, Young Whan Kim, Dae Seog Heo, Yung Jue Bang, Sung Koo Han, Young Soo Shim, Noe Kyeong Kim; Cancer Res Treat. 2001;33(5):373-376. Published online October 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.5.373

Abstract PDF

PURPOSE
Platinum-based chemotherapy has conferred a modest but significant survival benefit and the introduction of newer drugs has led to achieve higher response rate in patients with advanced non-small cell lung cancer (NSCLC). We performed a phase II trial in order to evaluate the efficacy and toxicity of combination chemotherapy with vinorelbine (Navelbine) and cisplatin in advanced NSCLC.
MATERIALS AND METHODS
Patients with previously untreated, unresectable stage IIIB or IV NSCLC with measurable lesion (s) were eligible for entry into the study. NP chemotherapy consisted of intravenous vinorelbine 25 mg/m2, on day 1 and 8, and intravenous cisplatin 80 mg/m2 on day 1; this cycle was repeated every three weeks.
RESULTS
A total of 33 patients were enrolled in the study between July 1999 and Feb 2000. Of the 30 patients deemed eligible for analysis, thirteen patients achieved a partial response and thirteen showed a stable disease. The overall response rate was 43.3%. The median duration of response was 5.7 months (95% CI: 2.8~8.5 months). The median time to progression was 7.6 months (95% CI: 5.5~9.7 months) and the overall median survival time was 15.1 months (95% CI: 9.8~20.4 months) in the intent-to-treat analysis. Chemotherapy-related grade 3 or 4 toxicities were anemia in 1.5%, leukopenia in 4.5%, nausea/vomiting in 2.3%, alopecia in 13.3%, and neurotoxicity in 3.3%.
CONCLUSION
The combination of vinorelbine and cisplatin chemotherapy seems to be active and fairly tolerable in patients with advanced NSCLC.

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Clinical research on the efficacy of self-made sichongsan in combination with gefitinib on NSCLC patients with EGFR mutation
Yibo Zhao, Yu Dong, Shu Xing, Xueqi Fu
European Journal of Inflammation.2018;[Epub] CrossRef

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Discrepancies of the Values on the Withholding Futile Interventions between Physician and Family Members of Terminal Cancer Patients: Do Youn Oh, Mi Ra Kim, In Sil Choi, Yo Han Joh, Byung Su Kim, Do Yeun Kim, Jee Hyun Kim, Se Hoon Lee, Tae You Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; Cancer Res Treat. 2001;33(4):350-356. Published online August 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.4.350

Abstract PDF: PURPOSE
To analyze the controversies surrounding therapeutic decision-making and the withholding of life- sustaining treatments, values held concerning therapeutic interventions of terminal cancer patients are compared between physicians and family members.
MATERIALS AND METHODS
42 advanced or terminal stage cancer patients were enrolled for the study. The questionnaires were administered to the duty doctor and the family of the patients. Questions included whether to use new agents with a 15% partial efficacy and whether to use opioid analgesics, intravenous nutrition, a feeding tube, antibiotics, and hemodialysis. Additionally, we asked about the administration of CPR, ventilator application, and euthanasia. If the family permitted, the same questionnaires were given to the patients.
RESULTS
Of the 42 cases, 5 families refused to answer the questionnaire. Of the available 37 families, only 5 families permitted access to the patients. Of the 5 patients, 2 patients refused the questionnaire. Only 67.6% and 8.1% of families and the patients clearly understood the stage of cancer. The use of a new agent was accepted by 45.2% of the physicians and 45.9% of the families. The rankings of the acceptance of treatment in the physicians and in the families were similar. The concordance rate between the physicians and the families was lowest on ventilator application and CPR. 31% of the physicians and 43.2% of the families agreed on the issue of euthanasia.
CONCLUSION
Values held on issues like therapeutic decision-making and the withholding of life-sustaining treatments in terminal cancer patients are discordant between physicians and family members. In order to resolve controversies on the role of physicians in end-of-life decisions, the values of physicians as well as patients and their family members should be considered in the final decision-making process.

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Drug Resistance to 5 - Fluorouracil and Overexpression of Thymidylate Synthase mRNA in Human Gastrointestinal Malignancies: Tae You Kim, Baek Yeol Ryoo, Yung Hyuck Im, Yoon Koo Kang, Sang Jae Lee, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 2000;32(1):44-52.

Abstract PDF: 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

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The Effect of Combination Chemotherapy with Vinorelbine, Carboplatin, and Ifosfamide in Patients with Advanced Non-Small Cell Lung Cancer: Young Woo Lee, Baek Yeol Ryoo, Tae You Kim, Bong Seog Kim, Yeon Hee Park, Hyun Ju Hong, Jin Young Kwag, Sang Won Lee, Yoon Koo Kang; J Korean Cancer Assoc. 1999;31(6):1227-1235.

Abstract PDF: PURPOSE
Despite recent advances in chemotherapy, the treatment outcome of advanced non-small cell lung cancer (NSCLC) remains poor and NSCLC is still the predominant source of cancer-related mortality in worldwide. Thus, we evaluated the efficacy and safety of a combination chemotherapy with vinorelbine, carboplatin, and ifosfamide (NCI) in advanced NSCLC patients.
MATERIALS AND METHODS
A total of 26 patients was enrolled in this study between December 1997 and June 1998. All entered patients were treated with NCI combination chemotherapy (vinorelbine 25 mg/m2/day i.v. days 1 and 8; carboplatin 300 mg/m2/day i.v. day 1; ifosfamide 3 g/m2/day i.v. day I; and mesna 2.4 g/m2/day i.v. day 1 after completion of ifosfamide infusion, treatment repeated every 4 weeks).
RESULTS
Among 26 patients, 23 patients were evaluable. Nine out of 23 evaluable patients had a partial response (response rate 39%; 95% confidence interval 19~59%). The median survival of the total 23 evaluable patients was 7.4 (range; 3~9.3+) months. The median progression-free survival was 2.8 (range; 0~7.7+) months. Among total 70 cycles of chemotherapy, leukopenia of grade II or more was observed in 6%, and tbrombo- cytopenia of grade II or more in 1%. There was no treatment-related death. Main non-hematologic toxicities were nausea/vomiting, stomatitis and peripheral phlebitis, almost of which were tolerable.
CONCLUSION
NCI chemotherapy seemed to be moderately active and well tolerated in patients with advanced NSCLC.

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High-Dose Chemotherapy with Vandervilt Regimen and CSF Support for High-Risk Aggressive Non-Hodgkin's Lymphoma: Bong Seog Kim, Jeong Hoon Yang, Kyung Tae Kim, Baek Yeol Ryoo, Tae You Kim, Young Hyuck Im, Jhin Oh Lee, Tae Woong Kang, Yoon Koo Kang; J Korean Cancer Assoc. 1998;30(1):137-149.

Abstract PDF: PURPOSE
To detennine the therapeutic effect and toxicities of high-dose chemotherapy with Vanderbilt regimen and colany-stimulating factors(CSF) support for high-risk aggressive non-Hodgkin's lymphoma(NHL).
MATERIALS AND METHODS
Between Aug. 1995 and Mar. 1997, 40 patients with high-risk aggressive NHLs were treated with high-dose chemotherapy with Vandebilt regimen and CSF support. If the complete response(CR) was induced, four cycles of CHOP were administered for the maintenance of response. In cases of lymphoblastic lymphomas, CNS prophyiaxis with cranial irradiation and intrathecal methotrexate was done after CR.
RESULTS
CR was achieved after Vanderbilt regimen in 62.5%(25/40) of the total patients. CR rste in refractory group(12.5%: 1/8) was significantly lower than in other groups (75%: 24/32)(p=0.001). With a median follow-up of 14 months, the failure free survival (FFS) was 0~18+ months(median 6.1 months). The overall FFS rate at one year was 31.7%. The 1-year FFS rate in refractory group(0%) was significantly lower than in other patients groups(41%)(p=0.001). The range of survival time was 0.5~18+ months, and median survival time was 6.2 months. Grade 4 leukopenia was observed in 100% of chemotherapy cycles and its median duration was 7 days. However, only one patient died due to treatment-relate sepsis. Non-hematological toxicities were tolerable and all reversible.
CONCLUSION
High-dose chemotherapy with Vanderbilt regimen was effcctive for induction of CR in high-risk aggressive NHL patients and safe with the CSF support. However, poor CR rate in reftactory group and poor FFS in other groups indicate that a new, more intensive approach is needed for the induction of CR in refractory group and for the maintenance of CR in other high-risk patient groups.

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A Phase 2 Trial of EPOCH (Etoposide, Vincristine, Doxorubicin, Cyclophophamide and Prednisolone) Chemotherapy for Previously Treated Non - Hodgkin's Lymphoma: Baek Yeol Ryoo, Tae You Kim, Young Hyuk Im, Jhin Oh Lee, Taik Koo Yun, Keun Chil Park; J Korean Cancer Assoc. 1998;30(1):127-136.

Abstract PDF: 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.

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Prognostic Factor Analysis of Small Cell Lung Cancer: Appropriateness of Two Staging System: Jae Jin Chang, Tae You Kim, Choon Taek Lee, Seung Mo Nam, Jae Hag Kim, Eun Jeong Song, Seong Hwan Kim, Bong Seog Kim, Baek Yeol Ryoo, Young Hyuck Im, Jhin Oh Lee, Tae Woong Kang, Yoon Koo Kang; J Korean Cancer Assoc. 1997;29(6):1000-1010.

Abstract PDF: PURPOSE
The two staging system, which divides the tumors into limited disease (LD) and extensive disease (ED) has been widely accepted as a major prognostic determinant in small cell lung cancer (SCLC). However this system has provoked several controversial issues in defining stage categories, for instance, ipsilateral pleural effusion as LD or ED. Furthermore, identification of favorable subgroups in the same stage has been recognized as an important factor to determine appropriate treatment strategies. In this study, we performed a retrospective analysis in an attempt to resolve the controversial issues about staging and identify the patient group with favorable prognosis based on this two staging system.
MATERIALS AND METHODS
The clinical data of 233 patients with SCLC treated from 1990 to 1996 at Korea Cancer Center Hospital were retrospectively analyzed for this study. All patients were treated with chemotherapy containing cisplatin and/or radiotherapy. The independent prognostic factors for survival were identified by multivariate analysis using Cox's proportional hazards model.
RESULTS
Performance status (relative risk of death [RR]:2.89), number of metastasis (RR:2.2), response to treatment (RR:2.2) as well as stage (RR:1.77) were identified as independent prognostic factors for survival in patient with SCLC. The median survival of patients with ipsilateral pleural effusion (13 months) which was categorized as ED was similar to that of patients with contralateral mediastinal or supraclavicular lymph nodes (13.8 months) or other LD patients (13.7 months). This result suggests that ipsilateral pleural effusion should be categorized as LD. In LD, response to treatment was the only independent prognostic factor (RR:2.34) and thoracic radiotherapy moderately improved survival as compared with combination chemotherapy alone (17.7 months vs. 10.4 months, p=0.06). In ED, the patient group with a good performance status (ECOG 0-1), normal range of serum alkaline phophatase, and metastasis less than 2 sites showed significantly prolonged survival, comparing with other ED patients (11.2 months vs. 7.2 months, p=0.0001).
CONCLUSION
As a result of survival analysis, we confirmed independent prognostic factors such as stage and performance status in SCLC. We could recommend that LD category include patients with ipsilateral pleural effusion as well as those with contralateral lymphadenopathy. In ED, the survival in patients with favorable prognostic factors was comparable to LD, suggesting this patient group may be a candidate for aggressive therapy.

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Clinicopathologic Charcteristics of Korean Non - Hodgkin's Lymphomas Based on REAL Classification: Yoon Koo Kang, Bong Seog Kim, Tae Won Kim, Mon Hee Ryu, Seung Sook Lee, Baek Yeol Ryoo, Tae You Kim, Young Hyuck Im, Kyoo Hyung Lee, Jooryung Huh, Dae Seog Heo, Yung Jue Bang, Chulwoo Kim, Jung Shin Lee, Byoung Kook Kim, Woo Kun Kim, Sang Hee Kim, Noe Kveong Kim; J Korean Cancer Assoc. 1999;31(4):641-652.

Abstract PDF: PURPOSE
Non-Hodgkins lymphoma (NHL) is recognized as not a single disease but a group of diseases heterogeneous in biology and clinical characteristics. Recently, a new pathologic classification system, the REAL classification, has been introduced into the clinic. Although REAL classification has tried to define the subtypes biologically more correctly, its clinical usefulness has not been established yet. A retrospective study was performed to define the clinical characteristics of Korean NHLs according to the REAL classification and to determine its clinical usefulness.
MATERIALS AND METHODS
Pathologies of NHLs managed at 3 major hospitals in Korea between 1989 and 1995 were reviewed with immunophenotyping to determine the pathologic subtypes according to REAL classification. Clinical characteristics at the presentation and treatment outcomes of the eligible patients were analyzed. To determine the differences from the NHLs in the western countries, data of Non-Hodgkins Lymphoma Classification Project (NHLCP) were also compared.
RESULTS
Total 802 cases were eligible for this study. Although it was similar to NHLCP study that B-cell subtypes were the majority and diffuse large B-cell lymphoma was the most common subtype, the proportion of T-cell subtypes were much higher in our patient population than in the western population. It was because peripheral T-cell lymphomas, angiocentric lymphoma in particular, were more common and follicular lymphomas were less common in our patients. Eleven common pathologic subtypes could be classified into 3 prognostic groups. Marginal zone B-cell lymphoma and lymphoplasmacytoid lymphoma of which 5-year overall survival rate (5-yOSR) were > 80% were classified in the good prognostic group. Precursor T-lymphoblastic lymphoma was classified in the poor prognostic group because its 5-yOSR was less than 30%. The other 9 subtypes were classified in the intermediate prognostic group with S-yOSR of 30-79%.
CONCLUSION
The clinical. character' tics and prognoses of Korean NHLs could be defined according to REAL classification. These information would be helpful for the clinicians in formulating treatment strategies of Korean NHLs according to REAL classification.

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A Case of Pyloric Obstruction Caused by Self-expandable Metallic Stent for Palliation of Malignant Dysphagia: Yeon Hee Park, Young Soo Do, Yoon Koo Kang, Nam Hyun Hur, Baek Yeol Ryoo, Tae You Kim, Young Hyuck Im, Jhin Oh Lee, Tae Woong Kang; J Korean Cancer Assoc. 1997;29(3):534-539.

Abstract PDF: 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.

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IMVP-16/Pd (Ifosfamide/Methotrexate/VP-16/Prednisone) Combination Chemotherapy for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma: Ki Hyeong Lee, Young Iee Park, Heung Moon Chang, Tae You Kim, Keong Hae Jung, In Suk Woo, Young Hyuck Im, Dae Seog Heo, Yung Jue Bang, Seonyang Park, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1997;29(3):486-494.

Abstract PDF: PURPOSE
IMVP-16 (Ifosfamide/Methotrexate/VP-16) regimen consists of drugs that are not commonly used as the first-line therapy of non-Hodgkin's lymphoma. This study was performed to determine the efficacy of this relatively non-cross resistant regimen, with the addition of prednisone, in patients with primary refractory or relapsed non-Hodgkin's lymphoma.
MATERIALS AND METHODS
Patients with primary refractory or relpased intermediate to high grade non-Hodgkin's lymphoma were treated with ifosfamide (1000 mg/m2 iv, D1-5 with mesna), methotrexate (30 mg/m2 iv, D 3 & 10), VP-16 (100 mg/m2 iv, D 1-3), and prednisone (120 mg devided by 3 doses, D1-5). The treatment was repeated every 3 weeks.
RESULTS
Between Jan. 1988 and Aug. 1993, thirty eight patients were included. In 33 evaluable patients (4 loss-to follow up and 1 ineligibility) the median age was 49 years. The common histologic types were diffuse large cell type (52%) and immunoblastic type (18%). The proportion of patients with relapsed and refractory NHL was 39% and 61%, respectively. The rate of complete remission was 21% (7/33) and overall response rate was 48% (16/33). The median-response duration was 8 months (1.5~45+). Hematologic toxicities were tolerable. Non-hematologic side effects were also tolerable including stomatitis, peripheral neuropathy, and toxic hepatitis. Three treatment-related deaths were associated with sepsis, ARDS (adult respiratory distress syndrome) and acute gastrointestinal bleeding.
CONCLUSION
Based on these results, IMVP-16/Pd combination chemotherapy seems to have a moderate efficacy for the relapsed or refractory non-Hodgkin's lymphoma with tolerable toxicities.

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The Efficacy of PEEL Chemotherapy and Identification of Favoranble Subgroups in Patients with Carcinomas of Unknown Primary Origin: Byung Kook Choi, Young Jin Yuh, Jeong Hoon Yang, Seong Bae Kim, Yeon Hee Park, Bong Seog Kim, Baek Yeo Ryoo, Tae You Kim, Young Hyuck Im, Yoon Koo Kang; J Korean Cancer Assoc. 1999;31(1):144-152.

Abstract PDF: PURPOSE
In order to evaluate the efficacy of PEFL (cisplatin, etoposide, 5-fluorouracil and leucovorin) chemotherapy and to identify favorable subsets, we conducted a phase II trial of PEFL regimen for patients with carcinomas of unknown primary origin (CUPO).
MATERIALS AND METHODS
A total of 38 patients was enrolled in this study between May 1995 and September 1997. CUPO was defined as the presence of metastatic cancer documented in the absence of an identifiable primary site. All entered patients were treated with PEFL combination chemotherapy (cisplatin 20 mg/m(2)/day i.v, days 1-5, etoposide 100 mg/m(2)/day i.v. days 1, 3 & 5, 5-fluorouracil 800 mg/m(2)/day continuous infusion days 1-5, and leucovorin 20 mg/m(2)/day i.v, days 1-5; repeated every 4 weeks). The end points of this study were response and survival. To identify favorable subsets, univariate and multivariate analyses were perfonned.
RESULTS
Among 38 patients, 29 had measurable lesions. Three (11%) out of 27 evaluable patients had a complete response and 7 (26%) had a partial response (response rate 37%; 95% confidence interval 19~55%). The median survival of the total 38 enrolled patients was 9.1 (range; 1~21.9+) months. The median progression-free survival of the 27 evaluable patients was 5.3 (range 0~ 16.0) months. Among total 132 cycles of chemotherapy, leukopenia of grade II or more was observed in 15% and thrombocytopenia of grade I in 4%. There was no treatment-related death. Main non-hematologic toxicities were nausea/vomiting (79%), stomatitis (70%), and neurotoxicity (33%). The prognostic factor analyses identified 2 favorable subgroups; One was the patient group whose disease had poorly differentiated histology and presented in cervical lymph node. This group of patients had better response rate than other patients (response rate; 71% vs 25%, p=0.02). The other was the patient group who had normal tumor markers (CEA, CA 125 and CA 19-9). This group of patients had better survival than other patients(median survival; 14.8 vs 8.4 months, p=0.05).
CONCLUSION
PEFL chemotherapy seemed to be moderately active and tolerable in patients with CUPO. Among heterogenous patients with CUPO, the subset with cervical lymph node and poorly differentiated histology responded better to the chemotherapy and those with normal tumor markers tended toward longer survival.

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Combination chemotherapy with cyclophosphamide, vincristine, procarbazine, prednisolone(C-MOPP) in Hodgkin's disease: Kyung Hae Jung, Dong Bok Shin, Hyun Ah Kim, Young Iee Park, Tae You Kim, Keun Chil Park, Yoon Koo Kang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1991;23(4):806-813.

Abstract PDF: No abstract available.

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A Case of Synchronous Triple Primary Cancers in Larynx , Esophageu , and Stomach: Gyo Seon Kwun, Kyung Tae Kim, Yong Cho Kim, Ju Byeung Sung, Young Wo Lee, Eun Jung Jang, Baek Yeol Ryoo, Tae You Kim, Young Hyuck Im, Yoon Koo Kang, Seung sook Lee, Jim Oh Lee, Tae Woong Kang; J Korean Cancer Assoc. 1996;28(5):888-897.

Abstract PDF: Multiple primary cancers can occur in up to 20% of primary aerodigestive tract cancer patients. The multiplicity of cancer in aerodigestive tract suggests that the exposure to common carcinogen may be the cause of multiplicity(field cancerization). Continuous alcohol drinking and smoking are considered to be the major factors in development of multiple cancers. Also, high frequency of genetic alterations in multiple primary cancer patients implys that the genetic instability such as replication error or mutation of tumor suppressor gene may play a role in the development of multiple primary cancers. We report a case of a 61 year-old man who had triple synchronous cancers in larynx, esophagus, and stomach. He was a heavy smoker of 30-pack-years and a heavy drinker. Pathological examination showed squamous cell carcinoma of larynx and esophagus, and adenocarrinoma of stomach, respectively.

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A Case of Ph chromosome - Negative , bcr / abl Rearrangement - Positive Chronic Myelogenous Leukemia Prasenting with Dermopathy and Lymphadenopathy: Young Wo Lee, Gyo Seon Kwun, kyung Tae Kim, Young Cho Kim, Ju Byeung Sung, Eun Jung Jang, Choon Hong Hwnag, Baek Yeol Ryoo, Tae You Kim, Young Hyuck Im, Yoon Koo Kang, Jhin Oh Lee, Tae Woong Kagn; J Korean Cancer Assoc. 1996;28(5):927-936.

Abstract PDF: Chronic myelogenous leukemia(CML) is a clonal stem cell disorder, characterized by markedly increased myelopoiesis and the presence of the Philadelphia(Ph) chromosome. Ph chromosome, the result of a translocation between the abl proto-oncogene on chromosome 9 and the bcr gene on chromosome 22, is found in more than 95% of CML patients. The remaining 5% of patients are classified as Ph chromosome-negative CML and the bcr/abl gene rearrangement is detectable in approximately 50% of these patients. These Ph chromosome-negative, bcr/abl rearrangement-positive patients have clincal course and prognosis very similar to those of Ph chromosome-positive CML patients. We experienced a case of Ph chromosome-negative, bcr/abl rearrangement-positive CML presenting with multiple skin lesions and lymphadenopathy in a 59-years-old man. Bone marrow aspiration and biopsy showed typical features of CML in chronic phase. Skin and lymph node biopsies showed extramedullary leukemic cell infiltration, suggesting aggressive phase of CML. While the chramosome study revealed normal karyotype, RT-PCR analysis revealed bcr/abl fusion transcripts. In spite of chemotherapy, he expired 13 months after diagnosis.

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Chemotherapy with Five-Day Continuous Infusion of 5-Fluorouracil (5-FU) Plus Cisplatin for Advanced Gastric Cancer; Significance of 5-FU Concentration Monitoring: Yeon Hee Park, Bong Seog Kim, Baek Yeol Ryoo, Tae You Kim, Young Hyuck Im, Ho Sang Shin, Yoon Koo Kang; J Korean Cancer Assoc. 2000;32(3):516-523.

Abstract PDF: PURPOSE
To investigate the therapeutic effects and toxicities of 5-day continuous infusion of 5-FU plus cisplatin FP chemotherapy in advanced gastric adendegrees Carcinoma and to elucidate the relationship between the pharmacokinetic (PK) parameters and therapeutic outcome.
MATERIALS AND METHODS
Patients with previously untreated advanced stomach cancer were treated with FP chemotherapy. Plasma concentrations of 5-FU were measured using gas chro matography method for 5 days. Correlation of PK parameters of 5-FU with clinical outcome after FP chemotherapy was studied.
RESULTS
Response rate of FP chemotherapy was 46% (95% C.I.: 30~62%). There was a wide range of difference in the concentration and area under the curve (AUC) of 5-FU from patient to patient. We could find significant differences in AUC of 5-FU between the responders and the non-responders (p<0.05).
CONCLUSION
We could confirm that FP chemotherapy was effective and tolerable for the treatment of advanced stomach cancer. The monitoring of plasma 5-FU concentration after chemotherapy and the adjustment of subsequent 5-FU dose seems to be necessary to improve the treatment outcome of FP chemotherapy.

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