Byoung-Yong Shim

Intravenous Oxycodone versus Intravenous Morphine in Cancer Pain: A Randomized, Open-Label, Parallel-Group, Active-Control Study

Objective To compare efficacy and safety of intravenous continuous infusion of oxycodone with morphine in patients with cancer pain. Methods A 5-day, randomized, open-label, exploratory study at 6 sites in the Republic of Korea. Sixty-six adults aged ≥19 years with moderate-to-severe cancer pain (Numeric Rating Scale [NRS] ≥ 4) were enrolled. The study group received intravenous (IV) oxycodone, and the comparator group received IV morphine which were titrated depending on pain intensity. The efficacy endpoint is change in average NRS score from baseline to Day 5. Other assessments included worst, current, and average pain intensity; patient satisfaction; medication dose; and adverse events. Results Both groups achieved >50% reduction in average pain intensity: from “moderate” at baseline (oxycodone versus morphine: 6.0 ± 1.8 versus 5.9 ± 1.4) to “mild” at Day 5 (2.5 ± 1.8 versus 2.8 ± 1.6). While this reduction was similar between groups (3.5 ± 2.2 versus 3.1 ± 1.8, P value = 0.562), oxycodone achieved faster pain relief (average pain: 3.0 ± 1.6 versus 3.9 ± 1.6, P value = 0.020) on Day 2 and significant NRS reductions for worst pain on Day 2 (P value = 0.045) and current pain on Day 2 (P value = 0.035) and Day 5 (P value = 0.020) compared to morphine. Patient satisfaction, adverse events, and adverse drug reactions were similar for both groups. Conclusions For Asian patients with cancer pain, IV oxycodone is faster acting and showed similar analgesic efficacy and safety profiles as IV morphine. This trial is registered with Clinicaltrials.gov NCT02660229.

Tumor necrosis as prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer.

722 Background: Association between treatment response on the basis of pathologic stage evaluated after radical tumor resection and patient prognosis was well established. The object of this study is that tumor necrosis factor after CRT is also important as treatment response. Methods: A total of 243 patients with locally advanced rectal cancer that underwent neoadjuvant CRT was included. Three treatment response groups were classified by their pathologic stage results: complete treatment response (CTR), intermediate treatment response (ITR), and poor treatment response (PTR). Three tissue necrosis groups were classified by tissue pathologic results: complete necrosis response (CNR), intermediate necrosis response (INR), and poor necrosis response (PNR). Results: Overall survival (OS) and recurrence free survival (RFS) rate at 3 years were 74.5% and 61.3%, respectively. The 3-year OS rates of the CTR, ITR, and PTR were 83.7%, 75.9%, and 69.7%, respectively (p<0.001); the 3-year RFS rates were 76.7%, 69.0%...

Reduced luminal circumference of tumors plays a key role in anorectal function during the early period after neoadjuvant chemoradiation therapy in rectal cancer patients

PurposeThe deterioration of anorectal function after neoadjuvant chemoradiation therapy (nCRT) combined with surgery for rectal cancer has not been well defined. The aim of this study was to evaluate the relationship between the tumor response to nCRT and changes in anorectal function during a short-term period after nCRT.MethodsWe analyzed 100 consecutive patients with available preoperative anorectal manometry data, both before and after nCRT, from 2010 to 2013.ResultsComparing the manometric data before and after nCRT, the values reflecting rectal sensory function after nCRT was significantly lower than those before nCRT. However, in patients who experienced changed tumor morphology and a reduction in luminal circumferential ratio (LCIR) of tumor after nCRT, the values reflecting rectal sensory function were significantly less decreased after nCRT. On multivariate analysis, the reduction of LCIR after nCRT was a very important factor preventing the impairment of anorectal function during the short-term period in terms of the first rectal sensory threshold (RST) (P = 0.002), the RST of “desire to defecate” (P = 0.006), and rectal compliance (P = 0.003). Additionally, in linear regression analysis, the RST for the desire to defecate was positively affected by tumor morphology (P = 0.015) and the reduced LCIR (P = 0.025), and rectal compliance was positively affected by the reduced LCIR (P = 0.001).ConclusionThe nCRT impaired significantly rectal sensory function during the short-term period after nCRT and before a radical operation. However, this reduced LCIR of tumors after nCRT may prevent or minimize impediments to anorectal function during the short-term period after nCRT.

Abstract 977: Combination treatment of pantoprazole and TRAIL reduce cell viability by activating caspase cascade and down-regulation of phosphorylated ERK in AGS cell line.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background Pantoparzole(PPZ) is a proton pump inhibitor which is known to have an apoptotic activity in gastric cancer cells. Meanshile, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells. However, some types of cancer cells, including AGS human gastric adenocarcinoma cells show resistance for the TRAIL-mediated apoptosis. This study was aimed to investigate the sensitizing effectcs of PPZ on TRAIL-mediated apoptosis in AGS cell line. Methods Sensitivity to TRAIL and activation of TRAIL-induced apoptotic pathways were analyzed in AGS cell lines. WST-1 method was used to evaluate cell viability; Western blots was used to evaluate TRAIL-induced apoptosis. Results TRAIL alone had little effect on apoptosis in AGS cells. However, treatment with TRAIL in combination with subtoxic concentrations of PPZ sensitized TRAIL-mediated apoptosis in AGS cells. Combined treatment of PPZ and TRAIL induced caspase(caspase-8, -9, -3) and the pro-apoptotic molecules (Bax). In addition, the down regulation of phosphorylated ERK were also found in cells treated with the combination of PPZ and TRAIL. Conclusion The combination of TRAIL and PPZ may be considered as an approach to overcome the resistance of TRAIL in cancer treatment. Citation Format: Sang Young Roh, Jae Ho Byun, Byoungyong Shim, Young Seon Hong. Combination treatment of pantoprazole and TRAIL reduce cell viability by activating caspase cascade and down-regulation of phosphorylated ERK in AGS cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 977. doi:10.1158/1538-7445.AM2013-977

Abstract 4663: Markers of anaerobic glycolysis as predictive factor in neoadjuvant chemoradiotherapy of rectal cancer

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to resistance of radiotherapy and chemotherapy. We investigate the relationship between biomarkers related to anaerobic glycolytic metabolism (glucose transpoter-1(GLUT-1), lactate dehydrogenase (LDH)-5 and pyruvate dehydrogenase kinase (PDK)-1) and prognosis. Methods: GLUT-1, LDH-5, PDK-1 expression determined by immunohistochemistry were assessed in 109 patients with rectal cancer treated with 5 flurouracil and leucovorin neoadjuvant chemoradiotherapy. Results: This study included 74 male and 35 female patients with a median age of 63 (range 53-70 years). Stage I, II and III accounted for 7.3%, 43.1% and 49.5%. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (425 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33 and surgery was done on 7 to 10 weeks after completion of all therapies. The down staging rate of this neoadjuvant therapy was 53% and pathologic complete response rate is 18.3%. High expression of GLUT-1, LDH-5, PDK-1 was observed in 34 (31.2%), 62 (56.9%) and 45 (41.3%) patients, respectively. A negative GLUT-1 was associated with a significantly higher rate of pathologic complete response compared to positive GLUT-1 (25.3% vs. 0.02%, p=0.006). LDH-5, PDK-1 was not correlated with down staging and complete response of chemoradiotherapy. Conclusions: The GLUT-1 expression is the predictive factor of pathologic complete response in rectal cancer patients treated with 5 flurouracil and leucovorin neoadjuvant chemoradiotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4663.