Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival. RESULTS: A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP. CONCLUSION: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

Chemotherapy versus Best Supportive Care in Advanced Biliary Tract Carcinoma: A Multi-institutional Propensity Score Matching Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. MATERIALS AND METHODS: Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. RESULTS: In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). CONCLUSION: Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.

Occurrence of colonic liposarcoma after retroperitoneal liposarcoma

No abstract available.

Anti-carcinogenic actions of glycoprotein conjugated with isoflavones from submerged-liquid culture of Agaricus blazei mycelia through reciprocal expression of Bcl-2 and Bax proteins / 동물의과학연구지

Glycoproteins isolated from fruit bodies and mycelial cultures of mushrooms exhibit anti-carcinogenic actions in human cancer cells and animal tumor cells by induction of apoptosis. Here, we report that isoflavone-conjugated glycoproteins (designate Gluvone), exhibit strong anti-carcinogenic effects on human breast cancer MCF-7 cells by induction of apoptosis. Gluvone with 9.4 kDa of molecular weight was isolated from submerged-liquid culture of Agaricus blazei mycelia (ABM) in soy flake-containing liquid medium. MCF-7 cells were incubated with various amounts of Gluvone (0~250 microM) for a period of 6 days. Gluvone exhibited anti-proliferative actions in a dose-dependent manner and 62% growth inhibition at 200 microM for 4 days relative to control. Hoechst 33258 staining analysis revealed that Gluvone induced formation of apoptotic bodies. Gluvone was associated with down-regulation of anti-apoptotic Bcl-2 protein expression as well as up-regulation of pro-apoptotic Bax protein expression. Gluvone treatment induced proteolytic activation of caspase-9 and caspase-3 through cytochrome c release from mitochondria to cytosol as well as concomitant degradation of poly (ADP-ribose) polymerase (PARP). In addition, Gluvone induced activation of caspase-8. Taken all together, these results indicate that the anti-proliferative effect of Gluvone is associated with induction of apoptotic cell death through the mitochondrial dysfunction pathway mediated by enhancement of Bax protein expression and suppression of Bcl-2 protein expression.

Outcomes of Third-Line Docetaxel-Based Chemotherapy in Advanced Gastric Cancer Who Failed Previous Oxaliplatin-Based and Irinotecan-Based Chemotherapies / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Little is known about outcomes in the use of third-line chemotherapy in cases of advanced gastric cancer (AGC). The primary aim of this retrospective study was to evaluate outcomes of docetaxel-based chemotherapy in patients with AGC that progressed after both oxaliplatin-based and irinotecan-based regimens. MATERIALS AND METHODS: Eligible patients were those with AGC who had previous chemotherapy including fluoropyrimidine and oxaliplatin as well as fluoropyrimidine and irinotecan and who received subsequent docetaxel-based chemotherapy. Thirty-five patients were retrospectively recruited from 5 medical centers in Korea. Patients received either weekly or 3 weekly with docetaxel +/- cisplatin. RESULTS: Thirty-one out of 35 patients were evaluated for treatment response. A total of 94 cycles of chemotherapy (median, 2; range, 1 to 7) were administered. The overall response rate was 14.3%, and the disease control rate was 45.7%. The median progression-free survival (PFS) was 1.9 months (95% confidence interval [CI], 1.1 to 2.7 months). The median overall survival (OS) was 3.6 months (95% CI, 2.8 to 4.4 months). PFS and OS were significantly prolonged in patients of the Eastern Cooperative Oncology Group, with performance status of 0 or 1 in multivariate analysis (PFS: hazard ratio[HR], 0.411; 95% CI, 0.195 to 0.868; p=0.020 and OS: HR, 0.390; 95% CI, 0.184 to 0.826; p=0.014, respectively). Four of the 35 patients enrolled in the study died due to infection associated with neutropenia. CONCLUSION: Our findings suggest that salvage docetaxel-based chemotherapy is a feasible treatment option for AGC patients with good performance status (PS), whereas chemotherapy for patients with poor PS (PS< or =2) should be undertaken with caution for those who previously failed oxaliplatin- and irinotecan-based regimens.

Evidence-based Guidelines for Empirical Therapy of Neutropenic Fever in Korea / 감염과화학요법

Neutrophils play an important role in immunological function. Neutropenic patients are vulnerable to infection, and except fever is present, inflammatory reactions are scarce in many cases. Additionally, because infections can worsen rapidly, early evaluation and treatments are especially important in febrile neutropenic patients. In cases in which febrile neutropenia is anticipated due to anticancer chemotherapy, antibiotic prophylaxis can be used, based on the risk of infection. Antifungal prophylaxis may also be considered if long-term neutropenia or mucosal damage is expected. When fever is observed in patients suspected to have neutropenia, an adequate physical examination and blood and sputum cultures should be performed. Initial antibiotics should be chosen by considering the risk of complications following the infection; if the risk is low, oral antibiotics can be used. For initial intravenous antibiotics, monotherapy with a broad-spectrum antibiotic or combination therapy with two antibiotics is recommended. At 3 5 days after beginning the initial antibiotic therapy, the condition of the patient is assessed again to determine whether the fever has subsided or symptoms have worsened. If the patient's condition has improved, intravenous antibiotics can be replaced with oral antibiotics; if the condition has deteriorated, a change of antibiotics or addition of antifungal agents should be considered. If the causative microorganism is identified, initial antimicrobial or antifungal agents should be changed accordingly. When the cause is not detected, the initial agents should continue to be used until the neutrophil count recovers.

Two patients with acquired hemophilia successfully treated with combination therapy including therapeutic plasmapheresis / 대한내과학회지

Acquired hemophilia is a rare disorder associated with fatal bleeding caused by the development of autoantibodies against factor VIII. Here, we report the cases of two young women with acquired hemophilia who presented with massive internal hemorrhage and purpura. Both patients were successfully treated with combination therapy including factor VIII or factor VIII bypassing agent, immunosuppressants, and therapeutic plasmapheresis.

A Phase II Study of Leucovorin, 5-FU and Docetaxel Combination Chemotherapy in Patients with Inoperable or Postoperative Relapsed Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To estimate the effect and toxicity of bimonthly low-dose leucovorin (LV) and fluorouracil (5-FU) bolus plus continuous infusion(LV5FU2) with docetaxel combination chemotheraphy in patients with inoperable or postoperative relapsed gastric cancer. MATERIALS AND METHODS: Total 27 patients are enrolled in this study. LV 20 mg/m2 (bolus), 5FU 400 mg/m2 (bolus), 5-FU 600 mg/m2 (24-hour continuous infusion) on day 1, 2, 15, and 16, docetaxel 60 mg/m2 (1-hour infusion) on day 15 every 4 weeks. RESULTS: Total of 141 cycles were administered and response rate were 36.8% with 2 complete response (10.5%) and 5 partial response (26.3%) in 19 evaluable patients. The median response duration is 8.1 months (95% CI, 4.0~12.1). The median progression-free survival time is 6.7 months (95% CI, 5.0~8.5) and the median overall survival time is 11.9 months (95% CI, 4.8~19.1). The grade 3-4 toxcity of neutropenia (24.8%) and anemia (11.3%), neutropenic fever (2.8%) is observed. The grade 1 toxcity of injection site reaction is observed all patients and the grade 1-2 toxcity of alopecia is observed 60%. CONCLUSIONS: LV5FU2 with docetaxel combination chemotheraphy is effective and tolerable in patients with inoperable or postoperative relapsed gastric cancer.

Differential antitumor effects of sequence-dependent model in tumor cell line: association with peroxiredoxin / 부인종양

OBJECTIVE: The efficacy of two-drug combination treatment may be schedule-dependent. We investigated a simulated in-vitro interaction between taxol and doxorubicin in a Cervical cancer cell line HeLa and the role of peroxiredoxin in cytotoxicity. METHODS: Two contradicting schedules of two drugs (taxol followed by doxorubicin or vice versa) were compared each other in terms of cytotoxicity in parental HeLa cell line and the peroxiredoxin (prx)-overexpressing variant. Cytotoxic activity was determined by MTT assay. Cell cycle pertubation was evaluated by flow cytometric analysis. Protein levels were determined by western blot. RESULTS: The sequential treatment of taxol followed by doxorubicin (T--

The Expression of Thymidine Phosphorylase in Cancer-infiltrating Inflammatory Cells in Stomach Cancer

Thymidine phosphorylase (TP) has shown to be up-regulated in several cancers and to play a role in angiogenesis and invasion. Most studies regarding TP have focused on cancer cells. Recently, evidences suggest that TP in cancer-infiltrating inflammatory cells (CIICs) also affect the cancer cell behavior. To evaluate the significance of TP expression of CIICs in gastric cancer, we assessed TP expression of cancer cells and CIICs separately using immunohistochemical assay on 116 paraffin-embedded tissue samples from stomach cancer patients and investigated their clinical significance. When subjects were divided into 4 groups according to the TP expression: cancer/matrix (+/+), C/M (+/-), C/M (-/+), and C/M (-/-), intratumoral microvessel density scores were higher in the C/M (+/-) group than in the C/M (-/-) group (p=0.02). For lymph node metastasis and survival, there were no significant differences among the 4 groups. However, there were significant differences in survival (p=0.035) and LN metastasis (p=0.023) between the two groups divided by TP expression of CIICs alone irrespective of TP expression of cancer cells. Taken together, this study suggested the TP expression in CIICs could affect lymph node metastasis and patients' survival in gastric cancer.

A Phase II Trial of Haptaplatin/5-FU and Leucovorin for Advanced Stomach Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Heptaplatin (SKI-2053 R) is a new platinum analogue, with a better toxicity profile than cisplatin, and has antitumor activity even in cisplatin resistant cell lines. 5-fluoruracil (5-FU) has shown synergy with platinum compounds. This phase II trial was designed to determine the efficacy and toxicities of heptaplatin/ 5-FU (5-fluorouracil) for treating stomach cancer. MATERIALS AND METHODS: Thirty-two patients with advanced, measurable gastric adenocarcinomas were enrolled in this trial. The treatment consisted of heptaplatin, 400 mg/m2/day (1 hour IV infusion), on day 1 and 5-FU, 800 mg/m2/day (12 hours IV infusion), on days 1 to 5. The cycles were repeated every 3 weeks. RESULTS: Of the 26 evaluable patients, 9 had partial responses and 1a complete response (overall response rate, 38%; 95% confidence interval, 19~57%). The median response duration was 23 weeks (range: 4~60 weeks). The median time to progression was 26 weeks (range: 3~68 weeks). The grades III-IV toxicities were mostly hematological toxicities: leucopenia was observed in 11 patients (35%) and thrombocytopenia 4 (13%). No definite neuropathy was observed. Grade I-II nephropathy was also noted: grade I high BUN/creatinine levels occurred in 5 patients (16%), grade II proteinuria 2 (6%), grade I proteinuria 5 (16%). Neutropenic fever developed in 5 patients (16%) and 1 died of pneumonia in a neutropenic state. CONCLUSION: This study suggests that the regimen of Heptaplatin/5-FU should be effective and have a favorable toxicity profile for the patients suffering with advanced stomach cancer.

A Phase II Trial of Docetaxel and Ifosfamide for Patients with Platinum-Resistant or Refractory Non-Small Cell Lung Cancer in a Salvage Setting / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We conducted a phase II study of docetaxel and ifosfamide chemotherapy for patients with platinum- resistant or refractory non-small-cell lung cancer (NSCLC) to evaluate the response and toxicity profiles as a salvage treatment. MATERIALS AND METHODS: Between July 2000 and July 2004, 40 patients who had previously received platinum- based regimen as the first-line or second-line therapy were enrolled in this study. The treatment consisted of a docetaxel 75 mg/m2 intravenous infusion on day 1 and intravenous ifosfamide 3 g/m2 with Mesna(R) uroprotectione on day 1 through 3. This regimen was repeated every 3 weeks. RESULTS: One hundred thirty cycles of treatment were given, with a median of 3 cycles (range: 2~6 cycles). All the patients were evaluable for the response rate and toxicity profile. The major toxicity was myelosuppression. Grade 3~4 neutropenia occurred in 30 patients (75%) during treatment. Febrile neutropenia occurred in 16 patients (40%). Five of 40 patients (12.5%) had a partial response (95% confidence interval, 3.3~21.7%). The median time to disease progression was 2.65 months (range: 2.02~3.20 months), and the median survival was 5.24 months (range: 2.99~7.49 months). CONCLUSION: Salvage chemotherapy with docetaxel and ifosfamide showed a low efficacy and a high proportion of severe neutropenia in patients with platinum-resistant or refractory advanced NSCLC.

The Differential Gene Expression Profiles between Sensitive and Resistant Breast Cancer Cells to Adriamycin by cDNA Microarray / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Adriamycin(R) is one of the most commonly used drugs in the treatment of breast cancer. This study was performed to understand the molecular mechanisms of drug resistance in breast cancer cells. MATERIALS AND METHODS: We have analyzed the MCF-7 breast cell line and its adriamycin-resistant variants, MCF-7/ADR using human 10 K element cDNA microarrays. RESULTS: We defined 68 genes that were up-regulated (14 genes) or down-regulated (54 genes) in adriamycin resistant breast cancer cells. Several genes, such as G protein-coupled receptor kinase 5, phospholipase A2, guanylate cyclase 1, vimentin, matrix metalloproteinase 1 are up-regulated in drug resistant cells. Several genes, such as interferon, alpha-inducible protein 27, forkhead box M1, mitogen-activated protein kinase 6, regulator of mitotic spindle assembly 1 and tumor necrosis factor superfamily are down-regulated in adriamycin resistant cells. The altered expression of genes observed in microarray was verified by RT-PCR. CONCLUSION: These findings show that cDNA microarray analysis can be used to obtain gene expression profiles reflecting the effect of anticancer drugs on breast cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.

3-week-scheduled combination chemotherapy of gemcitabine and cisplatin in patients with advanced NSCLC / 대한내과학회지

BACKGROUND: The combination chemotherapy of gemcitabine and cisplatin has been proven effective in the treatment of advanced non-small cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. We therefore started a phase II trial to evaluate efficacy, toxicity and dose intensity (DI) as three-week scheduled chemotherapy of gemcitabine and cisplatin. METHODS: Between October 2000 and March 2003, a total of 56 patients with stage IIIB and IV NSCLC were enrolled in this study. Treatment schedule consisted of gemcitabine 1200 mg/m2 i.v. on days 1 and 8, and cisplatin 80 mg/m2 i.v. on day 1 of each chemotherapy cycle followed by two weeks of rest. RESULTS: Forty-eight patients were evaluable in response and adverse effects in this study. The median DI was 529 mg/m2/week for gemcitabine (66%) and 22 mg/m2/week for cisplatin (83%). Partial response was observed in 23 patients. The overall response rate was 47.8% (95% confidence interval [CI], range from 33.6% to 61.9%). Anemia and thrombocytopenia were the main hematologic adverse effects, with 8.3% and 8.3% of patients experiencing grade III to IV toxicity, respectively. The median survival time was 11.78 months (95% CI, range from 8.59 to 14.97months). No significant differences in response rate were observed according to sex, age, histology and DI of gemcitabine and cisplatin. CONCLUSION: The 3-week-scheduled combination chemotherapy of gemcitabine and cisplatin has feasibility to treat advanced stage IIIB and IV NSCLC with modest adverse effects. The regimen deserves further evaluaton in a phase III prospective randomized trial.

Clinical Significance of the Levels of Serum Cholesterol in Patients with Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The relationship between serum cholesterol levels and mortality is complex. Serum cholesterol levels correlate positively with coronary artery disease, but some studies have suggested a negative relationship in cancer patients. Because the serum cholesterol levels are one of the most frequently assayed laboratory values, trends in the levels of cholesterol were investigated, in patients with gastric cancer and assumed a possible role in cancer screening. MATERIALS AND METHODS: The serum cholesterol levels were retrospectively analyzed in a group of 220 patients, diagnosed with gastric cancer, and in 177 healthy subjects. Anthropometric (body mass index: BMI) and biochemical indices of their nutritional status were also determined in the study subjects. Statistical analyses were performed by analyses of variance and covariance, and a discriminant analysis. RESULTS: The levels of serum cholesterol, albumin, Hb and the BMI were significantly lower in the gastric cancer-patients group than in the healthy-subjects group. The serum cholesterol and Hb levels were shown to be independent of each other, when adjusted for the effects of the BMI. In the patients with gastric cancer the levels of cholesterol and Hb showed decreasing tendencies as did the tumor extension, as defined by the TNM system. CONCLUSION: The serum cholesterol and Hb levels were significantly lower in patients with gastric cancer than in the healthy subjects, which seemed to be linked to the progression of gastric cancer. Therefore, further study is required for the serum cholesterol and Hb levels to be used as markers in cancer screening and its progression, in patients with gastric cancer.

Predictors of Smoking Cessation in Outpatients / 예방의학회지

OBJECTIVE: This study was conducted in order to investigate predictors of smoking cessation in outpatients. METHOD: Subjects were 401 adult smoking patients who saw their doctors in the outpatient setting at a university hospital, regardless of their willingness of otherwise in smoking cessation. Physicians delivered a brief, stop smoking prompt to all patients who smoked one or more cigarettes a day. Then they referred to on-site counselors who provided a brief, nurse assisted intervention with a survey to a randomly assigned intervention group (200 smoking patients), whom the counselors telephoned later to prevent relapse or promote the motivation to quit, or gave only a survey to a control group (201 smoking patients). After at least 5 months, self-reported current smoking cessation was confirmed later using cut-off values of 7 ppm or less in expired alveolar air after breath holding portable CO analyzer. RESULTS: After 5 months, subjects in the intervention group were 1.56 times (95% C.I. 0.89-2.73) more likely to quit smoking than those in the non-intervention group (14.0% vs. 9.0%). Willingness to quit smoking in a month, scheduled admission in a month, self efficacy score and FTND (Fagerstrom Test for Nicotine Dependence) score were all significantly related with smoking cessation. In stepwise multiple logistic regression, previous attempts to quit smoking were significant instead of self efficacy score. In the intervention group who had willingness to quit smoking in a month (132 smoking patients), FTND score, whether quit date was today, and whether quit promise paper was submitting were all significantly related with smoking cessation. In stepwise multiple logistic regression, scheduled admission in a month and whether quit date was today were significant predictor variables. Smoking cessation treatment should be tailored to individual smoking patients considering these predictors.

Proteomic Profiling of Human Small Cell Lung Cancer Cell Line NCI-H211 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Small cell lung cancer is one of the major causes of death from cancer worldwide. To explore the expressions of global protein in small cell lung cancer cells, a proteomic approach, to identify the proteins, was used and the establishment of a protein reference map attempted. MATERIALS AND METHODS: Two-dimensional gel electrophoresis (2-DE), with subsequent analysis by mass spectrometry (MS), was applied to the study of protein identification from a small cell lung cancer cell line, NCI- H211. The cells were lysed, and the extracts subjected to isoelectric focusing, with immobilized pH gradients, followed by second dimension SDS-PAGE. The polypeptides were identified by peptide mass fingerprinting, with MALDI-TOF MS, after in-gel protein digestion. RESULTS: From silver staining of the gel, around two thousands protein spots were separated by the 2-DE. Of these protein spots visualized in the gel, one hundred and ten were identified by peptide mass fingerprinting. Different proteins, such as enzymes, cytoskeletal proteins and proteins common to eukaryotic cells, were identified. CONCLUSION: The protein expressions of the small cell lung cancer cells were analyzed to establish a protein reference map. The reference map presented here may serve as a working tool for the further study of small cell lung cancer.

The Cell Cycle Regulatory Effects of High Dose 5-fluorouracil on Breast Cancer Cell Line

BACKGROUND: Chemotherapy with 5-fluorouracil (5-FU) has been one of the mainstay in breast cancer treatment. The effects of high dose 5-FU on cell cycle regulation were studied in breast caner cells. METHODS: A breast cancer cell line MCF-7 was used. Protein expressions of G1/S cyclins, p21(Waf1/Cip1), cdk2, E2F1 and retinoblastoma were tested by western blot analysis. Immunoprecipitation and immune complex kinase assay were done for the assessment of E2F1/RB interacton and the activity of cdk2 respectively. RESULTS: p21(Waf1/Cip1) expression was barely detectable in control cells. With addition of 5-FU level of p21(Waf1/Cip1) were induced and cyclin D3 level was decreased as cell growth decreases. In accordance with increased expression of p21(Waf1/Cip1), cyclin E-associated cdk2 kinase activity was reduced. Retinoblastoma protein (RB) became dephosphorylated and E2F-1 binding activity with RB was increased. CONCLUSION: In this situation of high concentration of 5-FU breast cancer cells tend to be G1/S cell cycle arrested. Overexpression of p21(Waf1/Cip1) and dephosphorylation of RB may mediate the effectss of 5-FU by inhibiting E2F-1 activity, which contributes to G1/S cell cycle arrest. These results could be an indicating landmark for further study of high dose chemotherapy with 5-FU.

Induction Chemotherapy Followed by Concurrent Chemoradiotherapy in Locoregional Esophageal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The object of this study is to evaluate the efficacy and toxicity of induction chemotherapy followed by concomitant chemoradiotherapy in locoregional esophageal cancer. MATERIALS AND METHODS: Between December 1992 and December 1999, 43 patients with locoregional esophageal cancer were enrolled in this phase II trial. Patients were treated with 2-cycles of induction chemotherapy followed by concomitant chemoradiotherapy. F-P chemotherapy consists of 1,000 mg/m2/Day of 5-FU as continuous infusion on day 1~5 and 80 mg/m2 of cisplatin as an intravenous bolus on day 1 and was repeated every 3~4 weeks. All patients received 60 Gy of external beam radiation concomitantly with F-P chemotherapy; intraluminal brachytherapy was added in 12 patients. A total of 4 cycles of chemotherapy were delivered. No further treatment was planned in patients who achieved complete remission after completion of the treatment. RESULTS: Among the 43 patients entered, 35 patients completed the protocol. Of the 35 evaluable patients, 12 patients (34%) achieved complete response and 13 patients (37%) achieved partial response. In 26 of 33 patients, dysphagia was improved. At a median follow-up of 22 months, the 2-year and 5-year survival rates were 39% and 19%, respectively. The median survival duration of the complete responder group was 69 months (4~100 months) and the 2-year survival rate of the complete responder group was 82%. Toxicities were tolerable, comprised of mucositis and cytopenia. CONCLUSION: Induction chemotherapy followed by concurrent chemoradiotherapy in locoregional esophageal cancer is well tolerated and effective.

Combination Chemotherapy with Mitomycin C, Vinorelbine, and Cisplatin (MVrP) in Patients with Advanced Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A phase II study was conducted in patients with advanced non-small cell lung cancer (NSCLC) in order to evaluate the efficacy and toxicity of the combination chemotherapy regimen of mitomycin C, vinorelbine, and cisplatin (MVrP). MATERIALS AND METHODS: Between June 1996 and December 2000, fifty-nine patients with unresectable stage IIIB to IV, pathologically documented NSCLC were enrolled in this study. One cycle consisted of mitomycin C 10 mg/m2 i.v. day 1, vinorelbine 30 mg/m2 i.v. days 1 & 15, and cisplatin 80 mg/m2 i.v day 1 and the next cycle consisted of vinorelbine 30 mg/m2 i.v. days 29 & 43, and cisplatin 80 mg/m2 i.v day 29. Each cycle was alternated and treatments were repeated every 8 weeks. RESULTS: We were able to evaluate fifty-three of 59 patients. Objective responses were seen in 22 (41.5%) patients (CR 0%, PR 41.5%). The median duration of response was 13.7 weeks and the median time to progression was 17.7 weeks. The median overall survival was 45.6 weeks. There was a significantly longer survival seen in responders (p=0.041). The toxicities of this regimen were acceptable without treatment related toxic death. CONCLUSION: This study suggests that a combination regimen of mitomycin C, vinorelbine, and cisplatin is relatively effective and well tolerated for the treatment of advanced NSCLC.