Ji Yeon Baek

KRAS mutation status and clinical outcome of preoperative chemoradiation with cetuximab in locally advanced rectal cancer: a pooled analysis of 2 phase II trials.

PURPOSE Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. METHODS AND MATERIALS We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m2 weekly and 1650 mg/m2/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m2 on 1 week before radiation, and 250 mg/m2 weekly thereafter. RESULTS Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. CONCLUSIONS In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab.

Dipeptidyl Peptidase 10, a Novel Prognostic Marker in Colorectal Cancer

Purpose The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood. Materials and Methods The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes. Results DPPIV was not expressed in normal colon mucosa, but it showed luminal expression in 52 of the 383 colorectal cancers (13.5%). DPPIV expression in tumors was associated with right-sided location of the colon (p=0.010) and more advanced tumor stage (p=0.045). DPP10 was expressed in normal colonic mucosa, but its expression varied in primary colorectal cancer tissues. Loss of DPP10 expression was found in 11 colorectal cancers (CRCs) (2.9%), and multivariate analysis showed that loss of DPP10 expression was an independent factor for poor patient prognosis (p=0.008). Conclusion DPP10 may play a role in disease progression of colorectal cancer and loss of DPP10 expression in primary CRC is significantly associated with poor survival outcomes.

Primary Systemic Anaplastic Large Cell Lymphoma in a Single Korean Institution: Clinical Characteristics and Treatment Outcome

Despite advances in the characterization of anaplastic large cell lymphoma (ALCL), little data is available on Asian patients. We report here upon single Korean institutions experience regarding the clinical characteristics and outcomes of ALCL. We performed a retrospective study of 32 adults with ALCL. Most of the patients received anthracycline-based chemotherapy. Ann Arbor stage III-IV, B symptoms, high-intermediate/high International Prognostic Index (IPI), and extranodal disease at diagnosis were present in 56%, 44%, 41%, and 63%, respectively. Compared with Western studies, the male/female ratio (4.3) was markedly higher and skin (9%) and bone involvement (9%) were less frequent. The staining results for anaplastic lymphoma kinase were positive in 6 (33%) of 18 cases available. The complete response (CR) rate was 62% (95% CI, 44-80%). With a median follow-up of 51.0 months, 5 yr overall survival was 40±11%. The 3 yr relapse-free survival for the 18 patients who achieved CR was 74±12%. Age, performance status, lactate dehydrogenase, extranodal disease sites number, and IPI were correlated with treatment response and survival. Our data suggest that Korean ALCL patients appear to have a higher male/female ratio, less frequent skin/bone involvement, and lower CR rate compared with those of Western studies.

Open-label, Randomized Comparison of the Efficacy of Intravenous Dolasetron Mesylate and Ondansetron in the Prevention of Acute and Delayed Cisplatin-induced Emesis in Cancer Patients

PURPOSE The aim of this study is to compare the antiemetic efficacy and tolerability of intravenous dolasetron mesylate and ondansetron in the prevention of acute and delayed emesis. MATERIAL AND METHODS From April 2002 through October 2002, a total of 112 patients receiving cisplatin- based combination chemotherapy were randomized to receive a single i.v. dose of dolasetron 100 mg or ondansetron 8 mg, 30 minutes before the initiation of chemotherapy. In the ondansetron group, two additional doses of ondansetron 8 mg were given at intervals of 2 to 4 hours. To prevent delayed emesis, dolasetron 200 mg p.o. daily or ondansetron 8 mg p.o. bid was administered from the 2(nd) days to a maximum of 5 days. The primary end point was the proportion of patients that experienced no emetic episodes and required no rescue medication (complete response, CR) during the 24 hours (acute period) and during Day 2 to Day 5+/-2 days (delayed period), after chemotherapy. The secondary end points included the incidence and severity of emesis. RESULTS 105 patients were evaluable for efficacy. CR rates during the acute period were 36.0% for a single dose of dolasetron 100 mg, and 43.6% for three doses of ondansetron 8 mg. CR rates during the delayed period were 8.0% and 10.9%, respectively. There was no significant difference in the efficacy between the two groups. Adverse effects were mostly mild to moderate and not related to study medication. CONCLUSIONS A single i.v. dose of dolasetron 100 mg is as effective as three i.v. doses of ondansetron 8 mg in preventing acute and delayed emesis after cisplatin-based chemotherapy, with a comparable safety profile.