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Objective: We evaluated the characteristics of the gastrointestinal stromal tumors that showed discrepancies between their assessment using the Response Evaluation Criteria in Solid Tumor (RECIST) and Choi's criteria. We also investigated the clinical applicability of Choi's criteria to Korean gastrointestinal stromal tumor patients undergoing imatinib therapy., Methods: Patients with advanced gastrointestinal stromal tumors treated with frontline imatinib were analyzed. Computed tomography images of these patients were reviewed and genotyping for the KIT and PDGFRA genes was performed. Immunohistochemical staining of c-KIT, CD34, platelet derived growth factor receptor-alpha, platelet derived growth factor receptor-beta, AKT, P-ERK and vascular endothelial growth factor was followed., Results: Ninety-five patients were enrolled. When using Choi's criteria to evaluate the 61 patients who achieved at least partial response by Choi's criteria, 27 patients showed discrepancies in their response to treatment between these two sets of criteria. A lack of CD34 expression in tumors was found to be related to cystic degeneration after imatinib treatment (P=0.001). Patients who showed partial response by Choi's criteria but stable disease by RECIST criteria had a similar progression-free survival to cases who showed a partial response under both systems (P=0.951)., Conclusions: Gastrointestinal stromal tumors showing cystic degeneration after imatinib treatment lack CD34 expression. Choi's criteria have a clinical value in terms of the progression-free survival in Korean patients treated with imatinib.

Background: Recent studies have shown that the human epidermal growth factor receptor 2 status of a metastatic site may differ from that of the primary site. This difference may influence patient prognosis and response to therapy., Methods: We conducted a retrospective study using immunohistochemistry and/or fluorescent in situ hybridization to compare human epidermal growth factor receptor 2 and hormone receptor status in primary and metastatic breast cancers., Results: Fifty-six patients were included in this study. Conversion from hormone receptor positive in the primary tumor to hormone receptor negative in the metastasis occurred in 12 patients (21.4%), and hormone receptor negative to hormone receptor positive conversion occurred in two patients (3.6%). Human epidermal growth factor receptor 2 status was discordant between primary and metastatic lesions in seven patients (12.5%). All of the five patients who converted from human epidermal growth factor receptor 2 negative status to human epidermal growth factor receptor positive received trastuzumab-based chemotherapy. Overall response rate and median progression-free survival for concordant human epidermal growth factor receptor 2 positive patients were 69.2% and 16.9 months, whereas that of patients with positive conversion of human epidermal growth factor receptor 2 were 40.0% and 7.6 months, respectively (overall response rate; P = 0.169 and progression-free survival; P = 0.004)., Conclusion: Discordance in human epidermal growth factor receptor 2 and hormone receptor status between primary and metastatic tumors was observed, which led to altered treatment decisions. Evaluation of human epidermal growth factor receptor 2 and hormone receptor in metastatic tumors should be considered in patients with breast cancer.

Objective: The aim of this study is to evaluate the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin in gastric cancer patients and to assess prognostic factors affecting relapse and survival., Methods: We retrospectively reviewed the data of 153 patients with Stage III-IV (M0) gastric cancer. The patients were given adjuvant 5-fluorouracil/cisplatin chemotherapy after curative gastric resection with D2 dissection from November 1995 to November 2003. Chemotherapy consisted of cisplatin (60 mg/m(2) as 15 min i.v. infusion) and 5-fluorouracil (1200 mg/m(2) as 12 h continuous i.v. infusion for 4 days) in every 21 days up to six cycles., Results: During a median follow-up period of 72.9 months (range: 2.0-135.0 months), a total of 105 patients relapsed (locoregional 19.0% vs. systemic 81.0%). The median disease-free survival and overall survival were 19.8 and 32.2 months, respectively. Univariate analysis revealed T stage, TNM stage and lymph node ratio as prognostic factors for survival (P = 0.002, <0.0001 and <0.0001, respectively). After stepwise selection of the factors, multivariate analysis confirmed the impact of the lymph node ratio and T stage on overall survival and disease-free survival., Conclusions: In patients with Stage III-IV (M0) gastric cancer, adjuvant 5-fluorouracil/cisplatin chemotherapy was tolerable, but did not seem to confer survival advantage. And the lymph node ratio was found as an independent prognostic factor in this population. This evidence suggests that the clinical trial using more active chemotherapeutic agents is mandatory.

Objective: Metaplastic breast carcinomas (MBC) are a rare type of breast cancer and are generally characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) negativity. There is a paucity of information on prognosis according to hormone receptor and HER2 expression for these rare tumors. The aim of this study was to compare the clinical features and prognosis between triple-negative metaplastic carcinoma (TNMC) and non-triple-negative metaplastic carcinoma (NTNMC)., Methods: We retrospectively analyzed MBC patients treated at Seoul National University Hospital between 1996 and 2006. The medical records were reviewed., Results: Fifty-one patients were identified. At a median follow-up of 40.8 months, the 3-year disease-free survival (DFS) and overall survival (OS) rates were 75.5% and 86.3%, respectively. Non-triple negativity (P = 0.012) correlated significantly with OS in multivariate analysis. Of the 51 patients, 41 (80.4%) had TNMC and 10 (19.6%) had NTNMC. The two groups did not differ significantly by age, tumor size or nodal status. In patients with NTNMC, the positivity rates for estrogen receptor, progesterone receptor and HER2 were 20.0%, 30.0% and 80.0% in NTNMC. The 3-year OS rates in patients with TNMC and NTNMC were 93.4% and 58.2%, respectively (P = 0.007). With respect to DFS, there was no statistically significant difference between patients with TNMC and those with NTNMC (P = 0.149)., Conclusions: In MBC, the non-triple-negative group had a poor prognosis compared with the triple-negative group, which is contrary to what has been reported in patients with invasive ductal carcinoma of breast. Further research exploring the mechanism underlying this result is needed.

Objective: The aim of the study was to evaluate the role of ramosetron for the prevention of chemoradiotherapy-induced nausea and vomiting (CRINV) in patients receiving upper abdominal irradiation with concurrent 5-fluorouracil chemotherapy., Methods: Between November 2006 and April 2007, 25 patients with pancreatico-biliary cancer underwent adjuvant chemoradiotherapy. A total dose of 40 Gy was delivered using 2 Gy/fraction, 5 days a week, with 2 weeks of planned rest after 20 Gy. Concomitant 5-fluorouracil (500 mg/m(2)/day i.v. bolus) was administered for the first 3 days of each split course. During the first course of chemoradiotherapy, all patients had prophylactic metoclopramide before treatment and those refractory to metoclopramide received rescue medication with ondansetron. During the second course of chemoradiotherapy, prophylactic ramosetron was given to patients who were refractory to ondansetron. Response to antiemetics was scored in four tiers: none, no CRINV; mild, did not interfere with normal daily life; moderate, interfered with normal daily life and severe, patient bedridden because of CRINV., Results: Fifty-six percent of the patients (14 of 25) had moderate CRINV despite metoclopramide, and received ondansetron. Ten patients who experienced moderate CRINV despite the ondansetron had prophylactic ramosetron, and 60% of the patients (6 of 10) had the symptom improved., Conclusions: Ramosetron proved to be an effective alternative for the control of CRINV during upper abdominal irradiation with concurrent 5-fluorouracil chemotherapy.

Objective: We analysed the efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) chemotherapy as second-line treatment for metastatic or relapsed gastric cancer (MRGC) in a clinical practice setting. Factors to select patients who may benefit from salvage chemotherapy was also analysed., Methods: Patients with MRGC with progression on or within 6 months after discontinuing platinum-based chemotherapy received FOLFIRI as second-line therapy. The FOLFIRI regimen consisted of irinotecan (180 mg/m(2); day 1) combined with leucovorin (200 mg/m(2)), followed by 5-fluorouracil (400 mg/m(2)) as a bolus and 600 mg/m(2) as a 22-h infusion on days 1 and 2 every 2 weeks., Results: Fifty-one patients received a total of 282 courses of chemotherapy. No patients had complete remission (CR), but 9 patients achieved partial remission (PR). Stable disease (SD) was documented in 15 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.2 and 9.1 months, respectively. Toxicities were tolerable and grade 3/4 neutropenia was observed in 49 cycles (17%). In multivariate analysis, patients with less organ involvement by metastasis and good performance status (PS) were independently associated with a longer PFS and OS (P < 0.05). Disease control (CR, PR or SD) after first-line chemotherapy were related to a longer PFS (P = 0.02), but had no effect on OS., Conclusions: FOLFIRI was tolerable and showed modest activity as a second-line therapy in MRGC. Less organ involvement by metastasis or good PS may be optimal selection criteria for patients with MRGC who are suitable for second-line chemotherapy.

Objective: The aim of this study was to examine the appropriateness of chemotherapy and care in Korean cancer patients near the end-of-life., Methods: We designed a retrospective cohort composed of patients diagnosed as having metastatic cancer and who received palliative chemotherapy at Seoul National University Hospital in 2002. Two hundred and ninety-eight patients who died of cancer were evaluated in terms of the appropriateness of the cancer-care they received, including chemotherapy., Results: Median duration of chemotherapy was 6.02 months compared with 8.67 months for median overall survival. The median period between last chemotherapy and death was 2.02 months. Of the 298 patients, 50.3% received chemotherapy during the last 2 months of life. Furthermore, 17 patients (5.7%) died within 2 weeks after receiving chemotherapy. The proportion who visited an emergency room (ER) more than once during the last months of life was 33.6%, and the average number of ER visits after a diagnosis of cancer was 1.72. Only 9.1% of patients were referred to a hospice consultation service and only 11.7% of patients agreed with written DNR., Conclusions: Among patients who died of cancer, significant proportions were found to have received chemotherapy up to the end-of-life and to have visited ERs. Hospice referrals and discussions about DNR were not conducted well during the end-of-life period in Korea.

Background: The association of epidermal growth factor receptor (EGFR) mutations with the response to conventional cytotoxic chemotherapeutic agents in non-small-cell lung cancer patients has not been investigated. We retrospectively analyzed the associations between response to chemotherapy and molecular markers associated with gefitinib responsiveness including EGFR mutations., Methods: EGFR (exons 18, 19 and 21) and K-ras mutations (exon 2) were studied by direct sequencing and p-Erk and p-Akt expressions were studied by immunohistochemistry in archival paraffin embedded tissues. Response rate (RR) and time-to-progression (TTP) of prior chemotherapy by platinum, paclitaxel and gemcitabine were analyzed with respect to the presence of EGFR and K-ras mutations, and p-Erk and p-Akt expressions., Results: Of 90 patients investigated, 75 received platinums and 45 received paclitaxel as first-line chemotherapy agents. The RRS and TTPS of platinum- and paclitaxel-containing regimens were not affected by EGFR or K-ras mutations, nor by p-Erk or p-Akt expression. Fifty-seven patients received gemcitabine as first- or second-line chemotherapy. RR was not affected by EGFR or K-ras mutations or by p-Akt expression. However, all responders to gemcitabine exhibited (+) p-Erk expression [RR 30.6% for p-Erk (+) versus 0% for p-Erk (-), P = 0.01]. TTP was not affected by EGFR or K-ras mutations or by p-Erk or p-Akt expression., Conclusions: EGFR mutations did not affect response to conventional chemotherapeutic agents, namely platinums, paclitaxel and gemcitabine. Our results also suggest that it may be undesirable to use gemcitabine in patients with tumors not expressing p-Erk.

Background: Paclitaxel has shown promising activity in gastric cancer and has synergism with cisplatin. This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel (145 mg/m(2)) plus cisplatin chemotherapy in metastatic or relapsed gastric cancer., Methods: Chemotherapy-naïve patients with metastatic or relapsed gastric cancer were enrolled. Paclitaxel 145 mg/m(2) was administered intravenously over 3 h, followed by cisplatin 60 mg/m(2) on Day 1 every 3 weeks in the outpatient setting., Results: Of 39 patients enrolled, 17 (44%) had partial responses. Twelve (31%) had stable disease and eight (21%) progressive disease. Two patients (5%) were not evaluable because of early drop-out. The median time to progression was 4.7 months and the median overall survival was 12.1 months. The most common hematologic toxicity was anemia (41%). Grade 3/4 neutropenia and thrombocytopenia developed in 14 and 3%, respectively. The most common non-hematologic toxicities were peripheral neuropathy (43%) and emesis (43%). Grade 3/4 non-hematologic toxicities included emesis (11%), peripheral neuropathy (3%), diarrhea (3%) and hepatotoxicity (3%)., Conclusions: Low-dose paclitaxel and cisplatin chemotherapy was active and well-tolerated in chemotherapy-naïve gastric cancer patients. This regimen seems to have comparable efficacy to previously reported higher-dose paclitaxel plus cisplatin-containing regimens and fewer toxicities.

Background: Our objective was to verify the efficacy and safety of "docetaxel + 5-fluorouracil + cisplatin" 3-day combination chemotherapy as a first-line treatment in patients with unresectable gastric cancer., Methods: Between January and November 2002, we enrolled 43 patients [males 31; median age 55 years (range 24-74)] with inoperable gastric cancer who had not been seen previously in Seoul National University Hospital. The regimen used was docetaxel 70 mg/m(2) on day 1, cisplatin 40 mg/m(2) on days 2 and 3, and 5-fluorouracil 1200 mg/m(2) over 10 h on days 1-3, every 3 weeks., Results: A total of 168 cycles were administered. Mean cycle number per patient was 3.9. The administered dose intensity of docetaxel was 21.23 mg/m(2)/week, 5-FU 1092.14 mg/m(2)/week and cisplatin 23.82 mg/m(2)/week, which corresponded to 91.1, 91.0 and 89.5% of planned doses. Of the 43 patients, response evaluation was possible in 40 and, of these patients, 17 (42.5%) achieved a partial response, 13 (32.5%) stable disease, and 10 patients (25%) showed progressive disease. The median time to progression was 5.6 months [95% confidence interval (CI) 4.6-6.6 months]. Median overall survival was 9.0 months. (95% CI 4.8-13.2 months). Leukopenia occurred during 21.4% of cycles (36 of 168 cycles); 14.3% grade 1, 5.3% grade 2 and 1.8% grade 3. Anemia occurred in 16.7% (28 of 168 cycles); 11.3% grade 1, 4.8% grade 2 and 0.6% grade 3. Thrombocytopenia was not observed. Diarrhea, stomatitis and hypersensitivity occurred in 4.7% (two out of 43 patients), respectively. Neutropenic fever occurred in two patients (4.7%) and myalgia in three (7.0%)., Conclusion: "Docetaxel + 5-fluorouracil + cisplatin" 3-day combination chemotherapy is an active and tolerable regimen as a first-line treatment in patients with unresectable gastric cancer.

Objective: The objectives of the present study were to assess the efficacy and tolerability of perioperative paclitaxel/platinum-based chemotherapy and surgery in patients with stage IIIA clinical N2 (cN2) non-small cell lung cancer (NSCLC)., Methods: Clinical N2 was defined as either >15 mm or >10 mm and multiple nodes on computed tomography (CT) scan. Thirty-four chemotherapy-naive patients with stage IIIA cN2 received preoperative paclitaxel/cisplatin for two cycles and then underwent surgery. The treatment with paclitaxel/carboplatin was repeated for three cycles after the operation., Results: Of the 34 patients, none achieved a complete response (CR) and 22 achieved a partial response (PR), resulting in a response rate of 65%. Among 29 patients (85%) who had received thoracotomy, 25 (74%) underwent complete resection. Two pathological CRs were observed and mediastinal nodes were free of tumor in 21%. Grade 3-4 toxicity was uncommon and treatment-related mortality was not observed. The median time to progression (TTP) was 12.1 months [95% confidence interval (CI) 8.3-15.9 months] and median overall survival (OS) was 23.6 months (95% CI 17.7-30.2 months)., Conclusions: Paclitaxel/platinum-based perioperative chemotherapy and surgery for patients with stage IIIA cN2 NSCLC is effective and well tolerated.

Objective: The effectiveness of capecitabine, an oral fluoropyrimidine carbamate, is well documented in previously untreated metastatic colorectal cancer patients (overall response rate: 25%). However, its efficacy in patients with metastatic colorectal cancer refractory to 5-fluorouracil/leucovorin (5-FU/LV) has not been determined. This study was performed to evaluate the efficacy and to identify the side-effects of capecitabine in patients with metastatic colorectal cancer showing progression despite 5-FU/LV-based combination chemotherapy., Methods: Fifty-one metastatic colorectal cancer patients who showed progressive disease in 5-FU/LV-containing regimens (median: two regimes) were treated with capecitabine 1,250 mg/m(2) twice daily (days 1-14 repeated every 3 weeks)., Results: Only one partial response was observed (response rate: 2%). Twenty-seven patients (53%) showed stable disease after two cycles. The median time to disease progression of either a partial response or stable disease was 3.4 months. Hand-foot syndrome was the main toxicity of capecitabine and occurred in 35% of cases (grade 3 or 4 in 6%). The median number of cycles administered was two and the relative dose intensity of capecitabine was 80%., Conclusion: The response rate to capecitabine was low in metastatic colorectal cancers that were refractory to 5-FU/LV-containing chemotherapy. However, disease stabilization was seen in a significant number of patients.