Sun Jin Sym

Docetaxel monotherapy as a second-line treatment after failure of fluoropyrimidine and platinum in advanced gastric cancer: experience of 154 patients with prognostic factor analysis.

OBJECTIVE To investigate the efficacy and safety of docetaxel monotherapy as salvage chemotherapy for advanced gastric cancer (AGC) in clinical practice and to determine the prognostic factors in these patients. METHODS We retrospectively reviewed the medical records of patients with AGC for whom fluoropyrimidine and platinum had previously failed and who had received docetaxel salvage monotherapy between December 2000 and March 2006. Docetaxel was administered at a dose of 75 mg/m(2) intravenously every 3 weeks with dexamethasone prophylaxis. RESULTS A total of 154 patients received 583 cycles of docetaxel with a median of three cycles per patient (range 1-10). The median age was 54 years (range 27-75 years). The objective response rate of 86 patients with measurable lesions was 14%, with 1 complete response and 11 partial responses, with a median response duration of 5.6 months. An additional 25 patients achieved stable disease. The median time to progression (TTP) for all patients was 2.6 months [95% confidence interval (CI), 2.2-2.9] and the median overall survival (OS) from the start of docetaxel chemotherapy was 7.2 months (95% CI, 5.9-8.5). The chemotherapy was generally well tolerated. Multivariate analysis showed that the Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 versus 2) was an independent prognostic factor for both TTP and OS. Disease status indicative of a relatively small tumor burden (resected metastatic or recurrent tumor) was a predictor for better TTP and good differentiation of the tumor was a predictor for better OS. CONCLUSION Docetaxel 75 mg/m(2) is relatively active and tolerable as a second-line salvage treatment after failure of fluoropyrimidine and platinum in general clinical practice for AGC.

Dose Escalation of Imatinib After Failure of Standard Dose in Korean Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumor

OBJECTIVE We evaluated the results of imatinib dose escalation in patients with advanced gastrointestinal stromal tumors (GISTs) after disease progression on standard-dose imatinib. METHODS Clinical data from patients with metastatic or unresectable GISTs whose dose of imatinib was increased after disease progression on imatinib 400 mg/day were retrospectively reviewed. RESULTS The 24 patients studied had a median age of 52 years. Imatinib dosing was escalated to 600 mg/day in 12 patients, then to 800 mg/day in four patients. The other 12 patients had dose escalation directly to 800 mg/day. Two patients (8.3%) achieved a partial response, and seven (29.2%) had stable disease. Six-month progression-free and overall survival rates were 33.3 and 70.7%, respectively. Dose escalation to 600 or 800 mg/day was generally well tolerated. CONCLUSION Imatinib dose escalation is feasible and well tolerated in patients with advanced GIST who progress on standard-dose therapy, producing clinical benefit in approximately 37% of patients.

Salvage chemotherapy with biweekly irinotecan, plus 5-fluorouracil and leucovorin in patients with advanced gastric cancer previously treated with fluoropyrimidine, platinum, and taxane.

Objectives:We retrospectively assessed the combination of biweekly irinotecan with 5-fluorouracil (5-FU), and leucovorin (LV) as salvage chemotherapy in patients with advanced gastric cancer (AGC) previously treated with fluoropyrimidine (F), platinum (P), and taxane (T). Methods:Between October 2003 and February 2006, all 131 patients with AGC were treated with irinotecan (150 mg/m2 on day 1), along with either FOLFIRI-1 (ie, LV (20 mg/m2 bolus) before 5-FU (1000 mg/m2 continuous infusion over 6-hour) on days 1–2), or FOLFIRI-2 (ie, LV (20 mg/m2 bolus) before 5-FU (400 mg/m2 bolus) followed by 22-hour continuous infusion of 600 mg/m2 on days 1–2), or FOLFIRI-3 (ie, 5-FU (400 mg/m2 bolus) followed by 46-hour continuous infusion of 2400 mg/m2 5-FU and 100 mg/m2 LV). Cycles were repeated every 2 weeks. Results:The median age of the patients was 52 years (range, 19–70 years). Patients received a median of 4 cycles of chemotherapy (range, 1–21 cycles). Of the 97 patients with measurable disease, 1 (1.0%) achieved a complete response, and 11 (11.3%) achieved partial responses, making the overall response rate 12.3%. The median time to progression (TTP) was 2.2 months (95% CI, 1.9–2.6 months) and the median overall survival (OS) was 6.2 months (95% CI, 5.6–6.9 months). Good performance status (P = 0.046), fewer metastatic sites (P < 0.001), and longer time to progression of previous chemotherapy (P = 0.006) were independent prognostic factors affecting OS. OS was longer with the FOLFIRI-1 regimen but not with statistical significance (P = 0.064). The treatments were generally well tolerated. Conclusions:In actual clinical practice, biweekly irinotecan with 5-FU and LV had modest activity and tolerability in AGC patients previously treated with F, P, and T.

Kinase Mutations and Efficacy of Imatinib in Korean Patients with Advanced Gastrointestinal Stromal Tumors

PURPOSE This study analyzed the relationship between treatment outcome and kinase mutational status in Korean patients with advanced gastrointestinal stromal tumors (GISTs). EXPERIMENTAL DESIGN Clinical data were collected from 113 consecutive patients with metastatic or unresectable GISTs treated with imatinib from June 2001 through June 2005 at five institutions in Korea. KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were examined. RESULTS The median patient age was 57 years (range, 31-82 years). The overall response rate was 67.2%. KIT mutations were found in exon 11 (n = 92, 81.4%) and exon 9 (n = 10, 8.8%). One patient had a PDGFRA exon 18 mutation. The overall mutation rate was 91.2%. Response rates were 68.4%, 50.0%, and 80.0% in patients with KIT exon 11 mutations, KIT exon 9 mutations, and no kinase mutations, respectively. With a median follow-up of 49.0 months, the median progression-free survival (PFS) time was 42.0 months and median overall survival (OS) time was not reached. PFS and OS times did not differ significantly according to KIT genotype. CONCLUSION This study was unable to find an association between KIT mutational status and clinical outcome of imatinib in Korean patients with advanced GISTs. There was a trend toward better outcomes for patients with wild-type KIT or exon 11 mutations compared with exon 9 mutations, although this was not statistically significant. Compared with previous studies in western populations, these results suggest that ethnic differences may influence the relationship between KIT genotype and clinical outcome to imatinib.

A Phase II Study of Cetuximab (Erbitux®) plus FOLFIRI for Irinotecan and Oxaliplatin-refractory Metastatic Colorectal Cancer

We have evaluated the efficacy and safety of cetuximab plus FOLFIRI for irinotecan and oxaliplatin-refractory colorectal cancers. From September 2004 to February 2006, 31 patients with metastatic colorectal cancer were treated with cetuximab (400 mg/m2 intravenously [IV] over 2 hr on day 1 followed by weekly 1-hr infusions of 250 mg/m2) plus bi-weekly FOLFIRI (irinotecan 150 mg/m2 IV over 90 min, and leucovorin 100 mg/m2 IV over 2 hr, followed by 5-FU 400 mg/m2 IV bolus on day 1, and followed by 5-FU 2,400 mg/m2 by continuous IV over 46 hrs). Patients received a median of four cycles (range: 1-23). Eight (25.8%) patients had confirmed partial responses and 10 (32.2%) had stable disease. After a median follow-up of 13.2 months for surviving patients, the median time to progression was 2.9 months, the median duration of response was 5.4 months, and the median overall survival was 10.9 months. Skin toxicity was observed in 25 patients (80.4%) including grade 3 in 6 patients (19.4%). Other common non-hematologic toxicities of all grades were mucositis (32.3%), asthenia (22.6%), diarrhea (12.9%), and paronychial cracking (12.9%). The combination of cetuximab with FOLFIRI was effective and tolerable in colorectal cancer patients heavily pretreated with a number of chemotherapy regimens.

Rituximab-ESHAP as a mobilization regimen for relapsed or refractory B-cell lymphomas: a comparison with ESHAP

BACKGROUND: It has previously been shown that ESHAP was an effective mobilization regimen for patients with pretreated lymphoma. To extend these observations, the efficacy and feasibility of rituximab plus ESHAP regimen in CD20+ B‐cell NHL were assessed.

Epidermal growth factor receptor mutation and pattern of brain metastasis in patients with non-small cell lung cancer.

Background/Aims We investigated the time taken for patients with metastatic non-small cell lung cancer (NSCLC) to develop brain metastases (BM), as well as their subsequent overall median survival following diagnosis, considering the epidermal growth factor receptor (EGFR) mutational status. Methods We retrospectively investigated the medical records of 259 patients diagnosed with advanced NSCLC from January 2010 to August 2013, who were tested for EGFR mutations. The time from the diagnosis of advanced NSCLC to the development of BM and the overall median survival after BM development (BM-OS) were evaluated and compared by EGFR mutational status. Results Sixty-seven patients (25.9%) developed BM. Synchronous BM occurred more often in patients with EGFR mutation type (MT) (n = 20, 27.4%) compared with EGFR wild type (WT) (n = 27, 14.5%, p < 0.009). The median BM-OS was significantly longer in patients with EGFR MT than in those with EGFR WT (25.7 months vs. 3.8 months, p < 0.001), and a similar trend was noticed for patients with synchronous BM (25.7 months for EGFR MT vs. 6.8 months for EGFR WT, p < 0.001). However, in patients with metachronous BM development, the difference in BM-OS between patients with EGFR MT (14.6 months) and EGFR WT (2.5 months) did not reach statistical significance (p = 0.230). Conclusions Synchronous BM was more common in NSCLC patients with EGFR MT than in those with EGFR WT. However, EGFR mutations were associated with significantly longer median BM-OS, especially when the brain was the first metastatic site.

Efficacy and safety of epirubicin and etoposide combination chemotherapy in advanced hepatocellular carcinoma: A retrospective analysis

Background and Aim:  Systemic treatments of advanced hepatocellular carcinoma (AHCC) have offered marginal clinical benefits. Recently, Italian investigators reported that etoposide and epirubicin combination (EE) chemotherapy was highly active against AHCC, with a response rate of 39% and a median overall survival (OS) of 10 months. We report our efficacy and safety results of EE in clinical practice.

Synchronous Peripancreatic Lymph Node Gastrinoma and Gastric Neuroendocrine Tumor Type 2.

A 34-year-old man was referred to our hospital with gastric polypoid lesions and biopsy-confirmed neuroendocrine tumor (NET). Computed tomography (CT) revealed a 3×3.5×8-cm retroperitoneal mass behind the pancreas, with multiple hepatic metastases. His serum gastrin level was elevated to 1,396 pg/mL. We performed a wedge resection of the stomach, a right hemi-hepatectomy, and a retroperitoneal mass excision. After careful review of the clinical, radiological, histopathological, and immunohistochemical findings, peripancreatic gastrinoma, and synchronous gastric NET were ultimately diagnosed. We reviewed a CT scan that had been performed 6 years previously after surgery for a duodenal perforation. There was no evidence of gastric or hepatic lesions, but the retroperitoneal mass was present at the same site. Had gastrinoma been detected earlier, our patient could have been cured using less invasive treatment. This case demonstrates how important it is to consider Zollinger-Ellison syndrome in patients with a recurrent or aggressive ulcer.

A prediction model for complete remission upon reinduction for patients with acute myeloid leukemia after failure of anthracycline and cytarabine standard chemotherapy

The aim of this study was to investigate clinical parameters that might predict complete remission (CR) following reinduction therapy in patients with acute myeloid leukemia (AML). We retrospectively analyzed outcomes in 142 patients who failed to achieve CR with standard anthracycline-plus-cytarabine induction chemotherapy (IND1) and who received the same regimen as a reduction therapy (IND2). The CR rate after reinduction was 54%. Multivariate analysis showed that the presence of peripheral blood (PB) blasts on the day of commencement of IND2 and ≥20% blasts in an interim BM sample taken during IND1 (C1-INT-BM) were independent risk factors for failure of remission. Our scoring system for prediction of CR after reinduction (CRAR score) included a favorable chromosome risk group, absence of PB blasts on the day of commencement of IND2, and ≤21% blasts in the C1-INT-BM. This scoring system predicted that the rates of CR in the four subgroups would be 92.1%, 68.9%, 29.5%, and 7.3%, respectively, in good agreement with observed CR rates. The CRAR scoring model might be associated with the possibility of achieving CR after reinduction, and may be helpful in choosing alternative strategy for AML patients refractory to standard induction chemotherapy, although further prospective validation is required.