Biomedical subjects

Jong Ho Chun

Publications and source records attributed to Jong Ho Chun.

8 recordsLinked to original sources

PubMed2006

A phase II trial of docetaxel plus capecitabine in patients with previously treated non-small cell lung cancer.

BACKGROUND: A combination of docetaxel (T) and capecitabine (X) showed synergistic effects in preclinical studies and phase III randomized trials of metastatic breast cancer. We conducted this phase II study to examine its efficacy in previously treated non-small cell lung cancer (NSCLC) patients. METHODS: Patient eligibility required advanced NSCLC with measurable lesion(s), at least one prior regimen failure and Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Treatment consisted of T 36 mg/m(2) i.v. on days 1 and 8 plus X 1000 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle (level I) or T 30 mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle (level II). RESULTS: A total of 35 patients (M/F=24/11) were enrolled; 29 had received one prior regimen and 19 had received platinum-based regimens. Significant non-hematologic toxicities were observed after the treatment given at level I, including one treatment-related death. Subsequently 29 patients were treated at level II. The treatment at level II was well tolerated with grade 3 or 4 neutropenia only in 10%, grade 3 asthenia in 21% and stomatitis in 14% of patients. Four (15%) of 27 evaluable patients had partial response (PR) at level II and eight (30%) had stable disease (SD). CONCLUSIONS: The TX regimen showed modest antitumor effects in patients with previously treated NSCLC. For further studies, we recommend T 30 mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle.

Adenocarcinoma↗

PubMed2006

HES1 inhibits cycling of hematopoietic progenitor cells via DNA binding.

Notch signaling is implicated in stem cell self-renewal, differentiation, and other developmental processes, and the Drosophila hairy and enhancer of split (HES) 1 basic helix-loop-helix protein is a major downstream effector in the Notch pathway. We found that HES1 was expressed at high levels in the hematopoietic stem cell (HSC)-enriched CD34+/[CD38/Lin](- /low) subpopulation but at low levels in more mature progenitor cell populations. When CD34+ cells were cultured for 1 week, the level of HES1 remained high in the CD34+ subset that had remained quiescent during ex vivo culture but was reduced in CD34+ cells that had divided. To investigate the effects of HES1 in human and mouse hematopoietic stem-progenitor cells (HSPCs), we constructed conditional lentiviral vectors (lentivectors) to introduce transgenes encoding either wild-type HES1 or a mutant lacking the DNA-binding domain (BHES1). We found that lentivector-mediated HES1 expression in CD34+ cells inhibited cell cycling in vitro and cell expansion in vivo, associated with upregulation of the cell cycle inhibitor p21(cip1/Waf1) (p21). The HES1 DNA-binding domain was required for these actions. HES1 did not induce programmed cell death or alter differentiation in HSPCs, and while short-term repopulating activity was reduced in HES1-transduced mouse and human cells, long-term reconstituting HSC function was preserved. Our data characterize the complex, cell context-dependent actions of HES1 as a major downstream Notch signaling regulator of HSPC function.

Animals↗

PubMed2005

Weekly docetaxel in combination with capecitabine in patients with metastatic gastric cancer.

Docetaxel (T) and capecitabine (X) are active agents against gastric cancer with synergistic antitumor effects. We conducted the current phase II study to assess the response rate and toxicity of combination TX regimen in patients with metastatic gastric cancer. Eligible patients were treated with docetaxel (36 mg/m2 intravenously) on days 1 and 8 and capecitabine (1000 mg/m2 orally twice a day) on days 1-14 of a 3-week schedule until progression occurred. From December 2001 to May 2003, 55 patients with median age of 54 years (range, 22-73 years) were enrolled; 47 patients had measurable lesions. A total of 358 courses of treatment were given, with a median of 5 (range, 1-22+) per patient. Objective responses were documented in 19 of 47 patients with measurable lesions (response rate, 40.4%; 95% confidence interval [CI], 25.9-54.9), with the median response duration of 5.6 months (range, 2.1-13.6+). At a median follow up of 15.9 months for all of 55 study patients, the median time to progression and survival were 4.5 months (95% CI, 3.4-5.6) and 12.0 months (95% CI, 7.5-16.6), respectively. Hematologic toxicities were mild to moderate, and the observed grade 3 nonhematologic toxicities, the most frequent of which was stomatitis, were generally manageable. Four patients experienced pneumonitis, but all of them responded to steroid treatment. The TX regimen was relatively well tolerated and effective against metastatic gastric cancer, with the added advantage of being an outpatient regimen.

Adult↗

PubMed2005

Phase II study of low-dose docetaxel/fluorouracil/cisplatin in metastatic gastric carcinoma.

OBJECTIVES: In several recent reports, docetaxel (75-85 mg/m2) combined with fluorouracil (5-FU) and cisplatin has shown considerable efficacy but significant toxicities, especially neutropenia, in patients with advanced gastric cancer. The authors tested the efficacy and safety of a lower dose (50 mg/m2) of docetaxel, combined with 5-FU and cisplatin, in metastatic gastric cancer (MGC). METHODS: Chemonaive patients with MGC received docetaxel (50 mg/m2 on day 1), cisplatin (80 mg/m2 on day 1), and 5-FU (1200 mg/m2 on days 1-3) every 21 days. RESULTS: Forty-seven patients with a median age of 55 years (range, 30-73 years) received a median of 4 cycles (range, 1-13+ cycles). Of the 42 efficacy-"evaluable" patients, 17 showed a partial response (response rate, 40%; 95% confidence interval [CI], 26-55) according to the independent review panel. With a median follow-up of 12.6 months for all patients, the median time to progression was 4.6 months (95% CI, 3.6-5.6 months) and overall survival was 9.7 months (95% CI, 8.4-11.0 months). Grade 3/4 neutropenia developed in 68% of patients, and febrile neutropenia/neutropenic infection occurred in 26%. The most common grade 3/4 nonhematologic toxicity was stomatitis (21%), followed by syncope (6%), diarrhea (4%), peripheral neuropathy (4%), dizziness (2%), constipation (2%), and abnormal liver function tests (2%). There was 1 possible treatment-related death. CONCLUSIONS: Lower dose (50 mg/m2) docetaxel combined with 5-FU and cisplatin was active in MGC with a tolerable toxicity profile.

Adult↗

PubMed2004

Increased expression of metallothionein is associated with irinotecan resistance in gastric cancer.

To gain insight into clinically relevant mechanisms of irinotecan resistance, we undertook oligonucleotide microarray analyses on paired malignant effusion samples obtained from eight gastric cancer patients treated with weekly irinotecan. Pretreatment and posttreatment (48 h) effusion samples were obtained for each patient, and the change in expression profile was compared between clinical responders and nonresponders. When differences in the expression of genes were examined using SAM (Significance Analysis of Microarrays) software, five isoforms of the metallothionein family were identified to have significantly higher signal log ratios in five nonresponders, compared with three responders. Compared with control cells, metallothionein 1X (MT1X)-transfected AGS cells showed a 1.4-fold higher irinotecan IC(50) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and tended to form more colonies. These findings collectively suggest that irinotecan-induced up-regulation of metallothionein might be associated with irinotecan resistance in patients with gastric cancer, although it remains to be confirmed in a larger data set.

Adult↗

PubMed2004

DNA microarray analysis of the correlation between gene expression patterns and acquired resistance to 5-FU/cisplatin in gastric cancer.

The mechanisms of intrinsic and/or acquired anti-cancer drug resistance have been described in in vitro resistance models, but the clinical relevance has remained undefined. We undertook a prospective study to identify correlations between gene expression and clinical resistance to 5-FU/cisplatin. We compared expression profiles from gastric cancer endoscopic biopsy specimens obtained at a chemosensitive state (partial remission after 5-FU/cisplatin) with those obtained at a refractory state (disease progression), using Affymetrix oligonucleotide microarray technology (U133A). Using 119 discriminating probes and a cross-validation approach, we were able to correctly identify the chemo-responsiveness of 7 pairs of training samples and 1 independent test pair. These exploratory data demonstrate that the gene expression profiles differ between chemosensitive and refractory state gastric cancer biopsy samples.

Adult↗

PubMed2004

Weekly irinotecan in patients with metastatic gastric cancer failing cisplatin-based chemotherapy.

BACKGROUND: The goal of this study is to determine the efficacy and toxicity of weekly irinotecan as second-line chemotherapy in advanced gastric cancer after failure of cisplatin-based regimen. METHODS: Gastric cancer patients failing cisplatin-based chemotherapy received 125 mg/m(2) of irinotecan weekly for 4 weeks followed by 2-week rest, until disease progression. RESULTS: Thirty-seven patients were enrolled into this study. The objective response was documented in seven of 35 patients with measurable lesion (response rate 20%, 95% CI: 6.1-33.9). Eight patients (22.9%) had stable disease and overall tumor control rate was 42.9%. The disease remained stable in both of two patients without measurable disease. At a median follow-up duration of 15.8 months, median time to progression and overall survival were 2.6 months (95% CI: 2.4-2.8) and 5.2 months (95% CI: 3.6-6.7), respectively. Neutropenia and diarrhea were the main toxicities. Among 37 patients treated, grade 3/4 (G3/4) neutropenia occurred in 43.2/24.3% of patients, respectively, and was accompanied with fever in three patients. Non-hematologic toxicities consisted mainly of delayed diarrhea (G3/4, 18.9/0%) and nausea/vomiting (G3/4, 18.9/0%). These toxicities were manageable and there was no treatment-related death. CONCLUSIONS: This weekly schedule of irinotecan was modestly active against cisplatin-refractory gastric cancer and relatively well-tolerated with appropriate dose modification.

Adenocarcinoma↗

PubMed2003

A phase II study of weekly docetaxel plus capecitabine for patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: Docetaxel is an active agent in advanced nonsmall-cell lung carcinoma (NSCLC) and demonstrates preclinical and clinical synergism with capecitabine. We conducted the current Phase II study to evaluate the efficacy and safety of the docetaxel/capecitabine combination in chemotherapy-naive patients with advanced NSCLC. METHODS: Eligibility required Stage IIIB or IV NSCLC, bidimensionally measurable disease, and an Eastern Cooperative Oncology Group performance score of 2 or lower. Treatment consisted of docetaxel 36 mg/m(2) intravenously on Days 1 and 8 plus capecitabine 1000 mg/m(2) orally twice per day on Days 1-14 of a 21-day cycle, for a maximum of 6 cycles. RESULTS: Of 39 patients enrolled, 39 and 36 patients were evaluated for toxicity and response, respectively. The overall response rate was 53% (95% confidence interval [CI], 37-69%) with 19 partial responses (no complete response). The median duration of response was 6.2 months (range, 2.1-15.7 months). At a median follow-up of 14.2 months, 19 patients died. The median overall survival time was 17.8 months, with a 1-year survival rate of 56.4% (95% CI, 40.9-72.0%). There were two treatment-related deaths (one death due to pneumonia and one due to sepsis). Hematologic toxicity was mild to moderate. Thirteen percent of the patients had Grade 3 or 4 neutropenia. However, Grade 2 or 3 nonhematologic toxicities were frequent, which included asthenia (51%), stomatitis (33%), hand-foot syndrome (33%), and diarrhea (29%). CONCLUSIONS: The docetaxel/capecitabine combination showed promising antitumor activity for chemotherapy-naive patients with advanced NSCLC, However, it was frequently associated with moderate-to-severe nonhematologic toxicities, suggesting clinical synergism in both efficacy and toxicity. Further adjustment of the dose schedule is recommended to maximize the therapeutic index.

Adult↗