Bong-Gun Seo

A phase II study of oxaliplatin with low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced gastric cancer

To determine the activity and toxicities of a low dose leucovorin (ldLV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin administered fortnightly (modified FOLFOX-4), as a first-line therapy for patients with advanced gastric cancer. Patients were treated with cycles of oxaliplatin 85 mg/m2 on day 1 plus LV 20 mg/m2, followed by 5-FU a 400 mg/m2 bolus and a 22 hour continuous infusion of 600 mg/m2 5-FU on days 1 – 2 every two week intervals. Forty-five patients were enrolled in this study. Forty-two patients were assessable for response. One of the 42 patients demonstrated complete response, and 20 partial responses, and overall response rate of 50%. The median time to progression and overall survival time were 7.7 months (95% CI: 3.6 – 11.9 months) and 11.2 months (95% CI: 9.1 – 13.3 months), respectively. Major hematologic toxicities included grade 1 – 2 anemia (39.7%), neutropenia (30.4%) and grade 3 – 4 neutropenia (10.9%). Twelve cycles were associated with neutropenic fever. The most common non-hematological toxicities were grade 2 nausea/vomiting (20%). There was no treatment related death. The modified FOLFOX-4 regimen was found to be a safe and effective first line therapy in advanced gastric cancer.

Oxaliplatin with Biweekly Low Dose Leucovorin and Bolus and Continuous Infusion of 5-fluorouracil (Modified FOLFOX 4) as a Salvage Therapy for Patients with Advanced Gastric Cancer

PURPOSE To determine the activity and the toxicity associated with a low dose regimen of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every two weeks (modified FOLFOX 4) as a salvage therapy for advanced gastric cancer patients. MATERIALS AND METHODS Between December 2003 and December 2004, 33 patients were enrolled in this study. The patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on the first day plus LV 20 mg/m(2) over 10 minutes. Subsequently, the patients were given a 5-FU bolus 400 mg/m(2) followed by a 22-hour continuous infusion of 600 mg/m(2) on days 1 approximately 2. The treatment was repeated at 2 week intervals. RESULTS The median age of the patients was 50 years (range: 31 approximately 74), 82% (27/33) had the Eastern Cooperative Oncology Group performance status was 0 and 1. Of the 30 patients who could be evaluated for their tumor response, 8 achieved a partial response, with an overall response rate of 26.7% (95% confidence interval (CI): 20.5 approximately 32.7%). Fifteen patients (50%) showed stable disease and 7 patients (23.3%) progressed during the course of treatment. The median time from the start of chemotherapy to progression was 3.5 months (95% CI: 2.6 approximately 4.4 months) and the median overall survival time was 7.9 months (95% CI: 5.9 approximately 9.9 months). The major grade 3/4 hematological toxicity encountered included neutropenia (45.4%) and thrombocytopenia (3.0%). Neutropenic fever occurred during only 2 of the 178 cycles. The most common non-hematological toxicity encountered was grade 1/2 nausea/vomiting, which occurred in 18.2% of patients, diarrhea in 12.1% and neuropathy in 15.2%. There were no treatment related deaths. CONCLUSION The modified FOLFOX 4 regimen appears to be a safe and effective salvage therapy for advanced gastric cancer patients.

Clinical Significance of Peroxisome Proliferator-Activated Receptor γ and TRAP220 in Patients with Operable Colorectal Cancer

Purpose The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARγ or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). Materials and Methods A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARγ and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. Results Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARγ and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARγ positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARγ and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). Conclusion TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARγ and TRAP220 represents a biomarker for good prognosis in CRC patients.

A Phase II Study of Paclitaxel and Cisplatin as Salvage Therapy for Patients with Advanced or Metastatic Gastric Cancer

PURPOSE To evaluate the therapeutic activity and safety of paclitaxel and cisplatin combination chemotherapy in patients with advanced or metastatic gastric cancers that are unresponsive to primary chemotherapy. MATERIALS AND METHODS Advanced or metastatic gastric cancer patients unresponsive to first line chemotherapy were entered into this trial. The treatment regimen consisted of paclitaxel, 175 mg/m(2) by 3-hour infusion on day 1, and cisplatin, 60 mg/m(2) by 1 hour infusion on day 1, with the treatment repeated every 3 weeks. RESULTS 37 patients were entered in this study, with 32 fully evaluable for response. 4 (13%), 13 (40%) and 15 (47%) patients achieved a partial response, stable disease and progressed, respectively. The median time to progression was 4.0 months (95% CI: 2.0 approximately 6.0 months), and the median overall survival was 12.6 months (95% CI: 5.5 approximately 19.7 months), with a 1-year survival rate of 54%. Of a total of 135 cycles of chemotherapy, grades 3 and 4 hematological toxicities were neutropenia (14%) and anemia (3%). Grade >or=2 neuropathy was observed in 6 patients (17%). CONCLUSION The combination of paclitaxel and cisplatin is an effective and tolerable salvage treatment modality for advanced gastric cancer.

Abstract 4664: CXCL14 and CXCR7 expression are upregulated in human squamous lung cancers

Purposes Lung squamous cell carcinoma (SQCC) is the second-largest histological subtype of non-small cell lung cancer, but relatively few biomarkers are available compared to adenocarcinoma. Recently, chemokines and their receptors have been suggested to play important roles in the initiation or progression of cancers. In this study we examined the expression of chemokines and their receptors in human lung SQCC. Methods For mRNA expression of chemokines their receptors study, tumors and their matched normal lung specimens were collected from fresh frozen samples of 10 patients. For immunohistochemistry (IHC) study, formalin-fixed paraffine-embedded samples of 35 patients with primary lung SQCC were collected. All samples were from patients who were subjected to curative surgical resection at Dongnam Institute of Radiological and Medical Sciences. The mRNA was extracted by Quiagen RNeasy kit and the human RT2ProfilerPCR arrays for Chemokines/Receptors (SA Biosciences) was employed to determine the mRNA expression. Also, IHC was used to demonstrate their protein expression. Results The expression profiles of 84 chemokines and their related genes were compared across the tumors and their matched normal lung tissues. Among them, mRNA expression levels of CXCL14 (p=0.000) and CXCR7 (p=0.025) were significantly upregulated in tumor. CXCL14 and CXCR7 protein expression by IHC were detected in 25 (71%, p=0.000) and 21 (60%, p=0.000) of 35 cases for tumor, respectively. However, normal lung tissues showed no protein expression for CXCL14 and CXCR7. We also analyzed the correlation between clinicopathologic features (age, stage, tumor size, lymph node involvement, lymphovascular and perineural invasion and differentiation of tumor) and protein expression of CXCL14 and CXCR7. Although not significant, CXCL14 protein expression was more detected in the advanced stage (stage I/II, 60% vs III/IV, 90%) (p=0.120), lymphatic invasion (Yes, 82% vs No, 41%) (p=0.146) and perineural invasion (Yes, 100% vs No, 57%) (p=0.067). CXCR7 protein expression was significantly higher in advanced stage (stage I/II, 11/24, 46% vs III/IV, 10/10, 100%) (p=0.005) and lymphatic invasion (Yes, 13/16, 81% vs No, 8/18, 44%) (p=0.039). Conclusions This study demonstrated that mRNA expression level of CXCL14 and CXCR7 were significantly higher in SQCC compared to those in normal tissue. CXCR7 protein expression was detected significantly higher in advanced stage and lymphatic invasion. Our results indicated that CXCL14 and CXCR7 might play important roles in carcinogenesis and further study to elucidate their role in SQCC is required. Citation Format: YoonHee Choi, Soo Young Chung, Yoo Sang Yoon, Jae Hyun Kim, Ha-young Lee, Kyung A Kwon, Bong-Gun Seo, Hee Sam Na, Sung Sook Lee. CXCL14 and CXCR7 expression are upregulated in human squamous lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4664. doi:10.1158/1538-7445.AM2017-4664