Treatment outcomes of sunitinib treatment in advanced renal cell carcinoma patients: a single cancer center experience in Korea

PURPOSE: The retrospective study was performed to assess the efficacy and toxicity profiles of sunitinib in Korean patients with metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: Between January 2005 and December 2008, 76 Korean patients with recurrent/metastatic RCC who received sunitinib were retrospectively reviewed. The primary end point was progression-free survival and the secondary end points were overall survival and response rate. We also assessed the toxicities associated with sunitinib treatment. RESULTS: Of the 76 patients, 69 (90.1%) were diagnosed with clear cell RCC. The median progression-free survival and overall survival were 7.2 and 22.8 months, respectively in overall patients. Sixty-two patients (81.6%) received 50 mg 4 week and 2 week off schedule, and 14 patients (18.4%) received 37.5 mg daily on a daily continuous schedule. The objective response rate and disease control rate were 27.6% and 84.2%, respectively. A dose reduction or reduction in dose due to adverse events occurred in 76% of the patients, whereas 11% of the patients had discontinued treatment. Other common laboratory abnormalities were increased serum creatinine (75.6%), elevated alanine aminotransferase (71.0%), neutropenia (61.8%), anemia (69.7%), and increased aspartate aminotrasferase (53.3%). Grade 3/4 toxicities occurred as follows: thrombocytopenia (38.2%), fatigue (10.5%), stomatitis (10.5%), and hand-foot syndrome (9.2%). CONCLUSION: Our results indicate that sunitinib treatment is effective and tolerable for ecurrent/metastatic RCC patients in Korea. Further studies with prognostic or biochemical factors are needed to clarify the different toxicity profiles of this studyope

The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma

PURPOSE: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. MATERIALS AND METHODS: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. RESULTS: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G→A or C→T) rather than a transversion mutation (G→T or G→C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. CONCLUSION: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.ope

Docetaxel versus paclitaxel combined with 5-FU and leucovorin in advanced gastric cancer: combined analysis of two phase II trials.

PURPOSE: This is an ad hoc analysis of two phase II studies which compared the efficacy and safety of two taxanes (paclitaxel and docetaxel) combined with 5-fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric adenocarcinoma who were untreated or had only received first-line chemotherapy, were treated with either paclitaxel (PFL; 175 mg/m(2)) or docetaxel (DFL; 75 mg/m(2)) on day 1, followed by a bolus of LV (20 mg/m(2) days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m(2) days 1~3) every 3 weeks. The primary endpoint was overall response rate (ORR) and the secondary endpoint included survival and toxicity. RESULTS: Sixty-six patients received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of 9.5 months, the progression free survival was 5.2 months (95% confidence interval [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL (p=0.17). The overall survival was also comparable between the patients who received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95% CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non-hematologic toxicities; specifically, grade >or=3 mucositis (5%) and diarrhea (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy (5%) were common in PFL. CONCLUSION: Thus, the two taxanes had similar efficacy in the treatment of advanced gastric cancer, but different toxicity profiles. Prospective comparative studies are required to further clarify the role of taxanes in the treatment of advanced gastric cancerope

A Case of Henoch-Shonlein Purpura Caused by Rifampin

Rifampin is one of the first line drugs for treating tuberculosis, but it might be associated with serious adverse effects, including renal failure. We report here on a case of a 57-year-old patient who developed Henoch-Shonlein purpura during antituberculosis therapy that included rifampin. The patient converted to negative on the AFB smear for tuberculosis two weeks after the initial administration of antituberculosis medication. After treatment for 60 days, this patient was diagnosed with Henoch-Shonlein purpura by the purpura lesion on the lower legs, the leukocytoclastic vasculitis, the renal impairment and the pathological examination. After stopping rifampin, the skin lesions disappeared in about 10 days and his renal function gradually improved. This case study showed that Henoch-Schonlein purpura can be caused by rifampin during antituberculosis therapy and we recommend that the use of rifampin should be restrained when clinical symptoms of Henoch-Shonlein purpura are observedope

병리학적 N3 병기로 진단받은 위암 환자의 예후

Dept. of Medicine/석사[한글] [영문] The aim of this study was to determine the prognosis and the recurrence pattern of pN3 stage gastric cancer patients after the curative resection, and to identify the prognostic factors according to the clinico-pathologic features. Between January 2000 and December 2004, I retrospectively reviewed the medical records of the patients as histological confirmed pN3 stage of gastric cancer without distant metastasis including peritoneal seeding, hepatic metastasis or para-aortic lymph node metastasis. They underwent both gastrectomy and D2 or D3 lymphadenectomy with a curative aim. I then analyzed the survival according to clinico-pathologic factors as age, sex, tumor location, the type of gastrectomy, the gross features of the tumor, tumor size, tumor differentiation, and the depth of invasion, Lauren classification, lymphatic invasion, vascular invasion, the number of dissected and metastatic lymph nodes and the proportion of metastatic lymph nodes to dissected lymph nodes, the node stage by the Japanese Classification of Gastric Cancer, involvement of perigastric lymph nodes which subdivided by Group 1 vs. others, and adjuvant chemotherapy. And I also examined recurrence pattern in pN3 gastric cancer patients.Out of 467 patients with stage IV gastric adenocarcinoma who received surgery, 260 patients underwent curative resection and they were pathologically staged as N3. Among these 260 patients, 179 patients were pN3 stage gastric cancer without distant metastasis. The median age was 62 years (range: 16-82 years). The most common site of gastric cancer was lower third of the stomach (48.6%). Among 179 patients, 84 patients (46.9%) were restaged as N2 stage and 18 patients (10.1%) were restaged as N1 stage by JCGC. The majority of patients were received adjuvant chemotherapy (75.4%). Among 179 patients, 123 patients (68.6%) had recurred and the majority of recurrent site of gastric cancer was peritoneal metastasis (30.9%). The 3-year and 5-year disease free survival rate were 16.2% and 9.5%, respectively. The median time to recurrence was 11.9 months (range: 0.5-108.2 months).For all the patients, the median follow-up period was 19.6 months (range: 0.5-108.2 months) and the median overall survival time was 19.6 months (95% CI, 15.17 ? 23.96). The 3-year and 5-year survival rate of the pN3 gastric cancer patients were 27.9% and 12.8%, respectively. The identified predictors for a worse prognosis were Borrmann type III and IV group (HR: 1.79, 95% CI, 1.12 ? 2.86, p = 0.020), the group without adjuvant chemotherapy (HR: 6.23, 95% CI, 3.08 ? 12.62, P < 0.0001), the number of dissected lymph nodes more than 65 (HR: 2.06, 95% CI, 1.31 ? 3.26, p = 0.002) and the ratio of metastatic lymph nodes between 66 and 100 (HR: 2.01, 95% CI, 1.15-3.53, p = 0.015) for the pN3 patients. I suggested that gastric cancer patients staged as pN3 only without distant metastasis had a different prognosis by clinico-pathologic features, especially by metastatic lymph node ratio and adjuvant chemotherapy. These pN3 gastric cancer patients needed aggressive adjuvant chemotherapy after curative gastrectomy for better prognosis.ope

Efficacy and feasibility of radiofrequency ablation for liver metastases from gastric adenocarcinoma

PURPOSE: Optimal treatment for liver metastases from gastric cancer remains a matter of debate. The aim of our study is to evaluate the efficacy of radiofrequency ablation (RFA) for the treatment of liver-only metastases from gastric adenocarcinoma. MATERIALS AND METHODS: We retrospectively reviewed medical records of 29 patients who developed liver-only metastases from gastric adenocarcinoma and subsequently underwent gastric resection and RFA (n = 20) or gastric resection and systemic chemotherapy (n = 9) between January 1995 and February 2008. Overall survival was estimated using the Kaplan-Meier method, and was compared using the log rank test to evaluate RFA efficacy. RESULTS: Twenty patients who underwent RFA showed a median overall survival of 30.7 months (range: 2.9 to 90.9 months), a median progression-free survival of 6.8 months (range: 0.8 to 45.2 months), and median overall one-, three-, and five-year survival rates were 66.8%, 40.1%, and 16.1% respectively. The RFA group showed a 76% decreased death rate compared to the chemotherapy-only group (30.7 months versus 7 months, hazard ratio, 0.24; p = 0.004). Most patients tolerated RFA well, and complications were found to be minor (transient fever (20%) and/or right upper quadrant pain (25%)). One case of treatment-related death occurred due to sepsis that originated from a liver abscess at the ablation site. CONCLUSIONS: The data suggest that a use of RFA as a liver-directed treatment may provide greater survival benefit than chemotherapy and is an alternative option for the treatment of liver-only metastases from gastric cancer.ope