Search

Background: This study was undertaken to identify predictors of the prescription of strong opioids, which are important for the management of severe cancer pain, by Korean physicians. Methods: A questionnaire based on a hypothetical case designed to assess the prescription of morphine by physicians was administered to 800 specialists in the Korea Cancer Association, of whom 147 (18.4%) responded, and to 2200 specialists in the Korean Academy of Family Medicine, of whom 388 (17.6%) responded. We used a multidimensional approach to identify the predictors of prescription of morphine by physicians. Results: In the hypothetical case scenario, only 16.5% of the respondents stated that they would prescribe morphine for severe cancer pain. Multiple logistic regression analysis showed that physicians with a positive attitude regarding opioid addiction [odds ratio (OR) 2.62; 95% confidence interval (CI) 1.54 ‐ 4.46], experience of pain assessment (OR 2.09; 95% CI 1.13 ‐ 3.87), recent residency training (OR 2.27; 95% CI 1.30‐ 4.0) and positive self-evaluation as an oncology specialist (OR 2.60; 95% CI 1.41 ‐4.78) were more likely to prescribe morphine. None of the 13 variables in the knowledge dimension significantly predicted prescription of morphine for severe cancer pain. Conclusions: The results of the survey suggest that we need to develop strategies to develop a positive attitude toward opioids, to increase experience in pain assessment and to improve cancer pain

Background: Intrahepatic cholangiocarcinoma is a chemoresistant cancer for which effective chemotherapy is not yet available. We investigated the efficacy and toxicity of the combination of gemcitabine and cisplatin as second-line chemotherapy in four patients with advanced, progressive intrahepatic cholangiocarcinoma. Methods: Four patients were enrolled who had previous chemotherapy with epirubicin, cisplatin and protracted infusion of 5-FU. All these patients treated with gemcitabine 1000 mg/m 2 intravenously (i.v.) on days 1 and 8 for 30 min, cisplatin 75 mg/m 2 i.v. on day 1 for 90 min, given every 21 days. Results: Two patients had partial response (PR), and two had stable disease (SD), with one of the latter showing a decrease in tumor size of 35%. Median time to progression was 5 months (range, 3-9 months) and median survival was 9 months (range, 8-16 months). Toxicity was mild and tolerable. Conclusions: Gemcitabine and cisplatin combination chemotherapy may be an effective regimen for advanced intrahepatic cholangiocarcinoma. Further study is warranted to determine the efficacy of this combination regimen.

Intrahepatic cholangiocarcinoma usually presents late in the clinical course and has a poor prognosis. No effective systemic therapy is currently available. This study aimed to determine the efficacy and toxicity of the ECF regimen (epirubicin, cisplatin. and 24-h continuous infusion of 5-FU) in advanced intrahepatic cholangiocarcinoma.On day 1, epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) were administered i.v., repeated every 21 days. 5-FU (200 mg/m(2)/day was given continuous i.v. via an ambulatory infusion pump throughout the treatment course. A total of 24 patients (15 men and nine women) with advanced intrahepatic cholangiocarcinoma between August 1996 and April 2002 were enrolled in this study.Of the 20 evaluable patients, two had partial response (10%) and nine had stable disease (45%), including two minor response. Grade 3/4 neutropenia was observed in six patients, while grade 3/4 thrombocytopenia was seen in five patients. There was no neutropenic infection or thrombocytopenic bleeding during any of the cycles of chemotherapy.ECF regimen is well-tolerated but is not an effective treatment for advanced intrahepatic cholangiocarcinoma. Newer clinical trials with combination drugs should be developed.

Palliative chemotherapy is used to prolong survival among elderly patients with inoperable gastric cancer (GC). We analyzed differences between single and combination first-line palliative chemotherapy among these patients. Included patients were >70 years old and were treated for GC at four clinical centers of the Catholic University of Korea. Baseline characteristics, the first-line chemotherapy regimen, treatment responses, toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated. Between 2005 and 2012, 178 > 70-year-old patients with GC received palliative chemotherapy using single or combination regimens. Median ages were 77 years (range 71–89) in the single regimen group (SG, 70 patients) and 73 years (range 71–81) in the combination group (CG, 108 patients). Patients in the SG received S-1 or capecitabine. The most common regimen in the CG was platinum combined with fluorouracil. The most common response in both groups was stable disease (SG, 45.7 %; CG, 48.1 %). In the SG and CG, median PFS times were 4.4 months (95 % confidence interval [CI] 2.85–5.95) and 4.1 months (95 % CI 2.62–5.57; P = 0.295), respectively; median OS times were 6.6 months (95 % CI 4.17–9.08) and 7.6 months (95 % CI 5.50–9.69; P = 0.782), respectively. Hematologic (P

Background Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. Methods From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. Results The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). Conclusions MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.

The aims of this study were to evaluate the differences in cancer prevalence and pain management between young and elderly patients. The patients were grouped into 3 groups. The prevalence of cancer pain was 50.0% in those younger than 65 years, 55.9% in those aged between 65 and 75, and 58.3% in those older than 75 years. The prevalence of cancer pain was higher for patients in advanced stages and with poor performance status. Using logistic regression analysis, we found that performance status has a significant correlation with cancer pain. Severe cancer pain occurred in 8.0% of the patient and was most prevalent in the advanced stage. Side effects of analgesics were observed in 24.5%. Cancer pain correlates with performance status and cancer stage but not significantly with age.

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35 mg/m(2)) intravenously on day 1 and 8 plus oxaliplatin (100 mg/m(2)) intravenously on day 1 every 3 weeks until disease progression or unacceptable toxicity.A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6 months (range, 1-48 months) were enrolled in this trial; 22 (64.7 %) patients had been exposed to both agents. Their median age was 58 years (range, 50-68 years). The overall response rate was 55.9 % (95 % confidence interval (CI), 38.3-73.5 %), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5 months (range, 9.2-50.7 months), the median progression-free survival for all patients was 5.3 months (95 % CI, 4.4-6.1 months) and the median overall survival was 13.8 months (95 % CI, 11.1-16.4 months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1 %) and diarrhea (17.6 %), respectively. Five patients (14.7 %) experienced febrile neutropenia.Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m(2) in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m(2) and 5-fluorouracil (5-FU) 400 mg/m(2) as a bolus followed by 600 mg/m(2) as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Four types of human hyaluronidases (rHuHyal-1, -2, -3 and -4) were transiently expressed and purified from Nicotiana benthamiana, and their biochemical characteristics were analyzed. The recombinant HuHyals were expressed via agrobacteria-mediated infiltration and generated and expressed in terms of micrograms per 5 leaves of N. benthamiana. Expressed recombinant HuHyals were purified using a His(6) tagging system and Ni column chromatography, respectively, at pH 8.0, after which the purified rHuHyals were concentrated for additional biochemical analyses. The four types of rHuHyals were allowed to react with hyaluronic acids and chondroitin sulfates. The biochemical properties of rHuHyal-1 fit those of the commercially available Hyal, PH-20, which was extracted from animal testes under acidic conditions (pH 3.5). However, rHuHyal-1 evidenced activity levels 2 to 6-fold greater than the three other rHuHyals (rHuHyal-2, -3 and -4) at pH 3.5. However, only rHuHyal-4 exhibited chondroitinase activity with both 6-S-chondroitin sulfate (chondroitin sulfate C) and 4-S-chondroitin sulfate (chondroitin sulfate A) as standard substrates. The results of zymography demonstrated that recombinant HuHyal 1 was modified by glycosylation, but Escherichia coli Hyal was not. This result demonstrated that plant-based rHuHyal was functionally active and evidenced biochemical characteristics and post-translational protein modifications similar to those of animal testis-derived Hyal.

Chemotherapy failure remains a significant medical problem in the treatment of neoplastic disease and is thought to be due to many different factors including membrane transport, p-glycoprotein in multidrug resistance, glutathione and its related enzymes, topoisomerase II and DNA repair. Glutatione is a major constituent of non-protein thiol and participates in detoxification of chemotherapy and radiation. Thus, glutathione concentration is correlated with sensitivity to alkylating agents and radiation, and increased in resistant cell lines. Buthionine sulfoximine (BSO) is an inhibitor of glutathione biosysthesis and may increase cytotoxicities of alkylating agents, including melphalan and cisplatin, and radiation in sensitive and resistant cell lines. We studied effects on cellular glutathione levels and cytotoxicites of cisplatin, carboplatin and radiation by BSO treatment in human stomach cancer cell line (SNU-1) and ovarian cancer cell line (OVCAR-3). The results were as follow: 1) After BSO treatment of 1 mM and 2 mM for 2 days, the intracellular thiol concentration was depleted to 75.7% and 76.2% in SNU-1, and 74.1% and 63.0% in OVCAR-3, respectively. 2) The intracellular thiol concentration in SNU-1 was depleted to 33.4% after BSO 2 mM for only 2 hours incubation and 71.5% after small amount of BSO (0.02 mM) for 2 days. 3) The recovery of intracellular thiol concentration required more than 3 days after BSO removal. 4) BSO inhibited partially the growth of SNU-1 and OVCAR-3. 5) The cytotoxicities of cisplatin and carboplatin were markedly enhanced both in SNU-1 and OVCAR-3 by BSO treatment. 6) The cytotoxicities of radiation was inceased in OVCAR-3 and SNU-1 by BSO treatment. Therefore, it is concluded that BSO can deplete effectively the intracellular thiol concentration and enhance the cytotoxicities of cisplatin, carboplatin and radiation.

Primary adenocarcinoma of the appendix is a rare malignancy that constitutes < 0.5% of all gastrointestinal neoplasms. Moreover, primary signet ring cell carcinoma of the appendix is an exceedingly rare entity. We have encountered 15 cases of primary appendiceal cancer among 3389 patients who underwent appendectomy over the past 18 years. In the present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with ovarian metastases and unresectable peritoneal dissemination occurring in a 67-year-old female patient. She underwent appendectomy and bilateral salpingo-oophorectomy with a laparoscopy procedure. She then received palliative systemic chemotherapy with 12 cycles of oxaliplatin, 5-flurorouracil, and leucovorin (FOLFOX-4). The patient currently is well without progression of disease 12 mo after beginning chemotherapy.

Purpose High-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) have been used for the treatment of clinically aggressive non-Hodgkin's lymphoma (NHL). However, the superiority of specific conditioning regimens has not yet been established. The present study evaluated the efficacy and toxicity of a conditioning regimen involving fractionated total body irradiation (TBI), and the use of Ara-C and melphalan (TAM) for clinically aggressive NHL. Materials and methods Between March 2002 and December 2004, 31 patients with aggressive NHL received fractionated TBI with a dose of 12 Gy over 3 days, and were administered 9 g/m(2) Ara-C and 100 mg/m(2) melphalan followed by autologous peripheral blood stem Cell Transplantation at the Catholic Hematopoietic Stem cell transplantation Center Korea. Patients that responded to first line chemotherapy and achieved complete remission (CR), or were in a first sensitive relapse were defined as having less advanced disease, while the other patients were defined as having more advanced disease. Results Objective responses were obtained in 24 of 31 patients (77.4%), comprising complete remission in 19 patients (61.3%) and partial remission in 5 (16.1%) patients. The median follow-up time was 28 months (range 1 approximately 62 months). At 3 years, the overall survival and event-free survival (EFS) rates were 62.3% and 47.3%, respectively. Patients with less advanced disease and more advanced disease showed 3-year EFS rates of 73.3% and 22.5 %, respectively (p=0.006). Early (within the first 100 days) treatment-related mortality occurred in 3 (9.7%) patients. Of the 31 total patients, 15 (48.4%) developed grade 3 mucositis, 22 (70.9%) developed neutropenic fever, and two (6.5%) developed interstitial pneumonia syndrome>grade 3. Conclusion The modified TAM conditioning regimen and ASCT appear to be a feasible treatment regimen for clinically aggressive NHL, particularly for patients with less advanced disease.

Background Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of therapy for patients with relapsed or metastatic colorectal cancer. Methods Between January 2002 and October 2004, 44 patients with histologically confirmed recurrent or metastatic colorectal cancer were enrolled. The chemotherapy regimen schedule consisted of 180 mg/m2 of irinotecan being administered intravenously (i.v) on Day 1,400 mg/m2 of 5-FU via i.v bolus with 600 mg/m2 of continuous infusion for 22 hrs on both Day 1 and 2, and 20 mg/m2 of leucovorin on both Day 1 and 2, repeated every two weeks. Results The overall response rate was 47.8%. Of the 40 evaluated patients, one had CR (2.3%) and 20 had PR (46.5%). Toxicities were mild and easily manageable. Three patients experienced 23 episodes of Grade 3/4 leukopenia., Only one patient developed Grade 3/4 diarrhea. None experienced Grade 3/4 thrombocytopenia. Conclusion Modified FOLFIRI with a low dose of LV is an effective and tolerable regimen for patients with recurrent or metastatic colorectal cancer.

The anthracyclines and taxanes are considered to be the most active drugs in metastatic breast cancer (MBC). We conducted a multicenter phase II study to evaluate the efficacy and tolerability of the docetaxel plus epirubicin combination chemotherapy as first-line treatment in MBC and performed a prospective assessment of the predictive values of circulating HER2 extracellular domain (ECD) and vascular endothelial growth factor (VEGF). Docetaxel 75 mg/m 2 and epirubicin 75 mg/m 2 were given intravenously every 3 weeks. Prophylactic G-CSF was not used. Pretreatment serum HER2 ECD and VEGF levels were measured by enzyme immunoassay. Forty MBC patients were enrolled, and 39 patients were evaluable for toxicities and 38 for response. Complete response was observed in 3 (7.9%) patients, partial response in 20 (52.6%) (overall response rate 60.5%), stable disease in 11 (28.9%) and disease progression in 4 (10.5%). After a median follow-up of 22.5 months, the median duration of response was 28 weeks, median time to disease progression was 32 weeks, and median survival was 15.8 months. Two-hundred and fifteen cycles of treatment were administered (median, 6 cycles per patient). Grade 3 and 4 neutropenia were observed during 24 (11.2%) and 74 (35%) cycles respectively, and grade 3 or 4 febrile neutropenia in 24 (11.2%) cycles. Elevated circulating HER2 ECD levels were found to be associated with a shorter response duration (p

Due to its greater convenience, a combination of uracil and tegafur (referred to as UFT) taken orally is an attractive alternative to continuous intravenous (i.v.) 5-fluorouracil (5-FU) infusion. This phase II study assessed the response rate and toxicity profile of the combination of epirubicin, cisplatin and UFT in patients with metastatic adenocarcinoma of the stomach.Epirubicin (50 mg/m(2)) and cisplatin (60 mg/m(2)) were administered i.v. to 35 patients with metastatic gastric carcinoma on day 1, and subsequently UFT (300 mg/m(2)/day) was administered orally in divided doses for 21 days. The treatment was repeated every 3 weeks. The response rate, time to disease progression, survival and toxic effects were analyzed.Thirty-two of the 35 enrolled patients were assessed subsequently for response. The median number of cycles was four. Thirteen patients (40.6%) showed partial responses, while none showed a complete response. The median time to progression of carcinoma was 20.4 weeks, and the median survival was 37 weeks. Grade 3 and 4 neutropenia was observed in 25% of patients. Grade 3 nausea and vomiting was observed in 28% of patients. No treatment-related death was observed. All patients received doses as planned, except for one who required a 75% dose reduction due to nephrotoxicity. Six of 132 cycles were delayed7 days after four cycles.The combination of epirubicin, cisplatin and UFT showed anticancer activity against metastatic gastric adenocarcinoma, had a tolerable toxicity profile and showed excellent patient compliance.

Aim: Capecitabine and cisplatin (XP) combination chemotherapy is one of the standard 1st line regimens for the treatment of metastatic gastric cancer (MGC). Sorafenib is a multi-kinase inhibitor with activity against angiogenesis and RAF-MEK-ERK pathway. In this study, we aimed to evaluate the efficacy of sorafenib (S) in combination with XP as the 1st line chemotherapy in MGC. Methods: This study was a randomized (1:1), open-label, phase II study. The patients (pts) with metastatic gastric or gastroesophageal junction adenocarcinoma with measurable lesion(s) were eligible. The primary endpoint was progression-free survival (PFS). XP + S consisted of capecitaine 800 mg/m2 po bid on days 1-14, cisplatin 60 mg/m2 iv on day 1, and sorafenib 400 mg po bid on days 1-21, every 3 weeks. XP consisted of capecitabine 1000 mg/m2 on days 1-14, and cisplatin 80 mg/m2 iv on day 1, every 3 weeks. XP was continued up to 8 cycles until disease progression or intolerance. Pts in XP arm were allowed to cross over to sorafenib alone when their diseases progressed. Results: Between Jan 2011 and Feb 2013, a total of 195 pts were randomized from 12 sites in Korea, China and Taiwan. Median age was 56 years. All pts had ECOG performance status 0-1. 19% of pts had prior gastrectomy. Overall response rate was 54% in XP + S arm, and 52% in XP arm (p = 0.826). With a median follow-up of 12.6 months (range, 0.1-29.2), median PFS assessed by independent review was 5.6 months in XP + S arm, and 5.3 months in XP arm (HR 0.92, 95% CI 0.67-1.27, p = 0.609). OS was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65-1.31, p = 0.661). Frequencies of grade 3/4 toxicities were similar between XP + S and XP arms, except neutropenia (21% vs 37%), febrile neutropenia (2% vs 6%), and palmar-plantar erythrodysesthesia syndrome (7% vs 1%). In 51 pts who crossed over to sorafenib alone in XP arm, there was no objective response and the median PFS was 1.3 months (95% CI, 1.2-1.7). Conclusions: The addition of sorafenib to XP chemotherapy was safe but not more effective than XP chemotherapy alone for the 1st line treatment of MGC. Biomarker analyses are now ongoing to identify potential patients who can get benefit with XP + S. Disclosure: Y. Kang: Honorarium, consultant for Bayer, Roche Research grant from Bayer, Roche. All other authors have declared no conflicts of interest.

Because dose intensity may be important as a determinant response to vinorelbine, we explored the possibility of increasing the dose intensity of vinorelbine on a daily x4 schedule.Between February 1998 and March 1999, 31 patients with previously untreated advanced non-small cell lung cancer were enrolled. Vinorelbine 15 mg/m2 and cisplatin 20 mg/ m2 were administered intravenously daily for 4 days and repeated every 21 days.A total 96 cycles were administered (median 3, range 1-6); 42% of vinorelbine and 39% of cisplatin injections were dose-reduced or delayed owing to toxicity. The actual dose intensity (DI) of vinorelbine was 17.7 mg/m2/week and that of cisplatin was 24 mg/m2/week. These figures represent 88 and 90% of the theoretical DI, respectively. The overall response rate was 40% (12/30, one CR). The main toxicity was myelosuppression: granulocytopenia WHO grade 3 and 4 in 24 patients (77%) and thrombocytopenia grade 3 in two patients (6%). The non-hematological toxicity was mild and tolerable. After a median follow-up of 7.5 months (range 3-21 months), the median progression-free survival and overall survival times were 5 months (95% CI, 3.8-6.2) and 8 months (95% CI, 4.5-11.5), respectively.This regimen has a comparable therapeutic activity in patients with advanced lung cancers. However, despite supportive care there were excessive hematological toxicities. In view of increased toxicity and similar efficacy, this regimen is not indicated outside a clinical trial.

136 Background: Gastric cancer (GC) is a second leading cause of death in Korean elderly cancer patients. Palliative chemotherapy would be an option of treatment in inoperable elderly GC patients for gaining survival time. We analysed the differences between single and doublet first line palliative chemotherapy in elderly GC patients. Methods: More than 70-year-old GC patients treated in the hospitals of the Catholic university of Korea were analysed. Baseline characteristics, first-line chemotherapy regimen, treatment responses, toxicities, time to progression (TTP) and overall survival (OS) were evaluated. Results: From 2005 to 2012, 178 GC patients above 70 years had been treated with palliative chemotherapy with single or doublet regimen. The median age were 77 years (range 70-89) in single regimen group (SG, 70 patients) and 73 years (range 70-81) in doublet regimen group (DG, 108 patients). TS-1 or capecitabine was used in SG, and platinum combined with 5FU or taxane was the most common regimen in DG. The most common response in both group was stable disease. Median relative dose intensity was 92.4% (range 50~100%) in SG and 83.5% (range 43~100%) in DG. Median TTP in SG was 4.40 months (95% CI, 2.85-5.95) and 4.10 months in DG (95% CI, 2.62-5.57, P=0.295). Median OS was 6.90 months (95% CI, 4.20-9.59) in SG, 8.20 months (95% CI, 5.96-10.43, p=0.918) in DG. Hematologic (P=0.03) and non-hematologic toxicities (p=0.061) were more frequent in DG. The common causes to terminate chemotherapy were disease progression in SG and decreased performance status in DG. Conclusions: No significant differences were observed in TTP and OS in both groups, but treatment related hematologic toxicity of SG was less than DG. Single agent treatment would be considered as the option of first line palliative chemotherapy in the elderly more than 70 years.

e15164 Background: Unresectable locally advanced adenocarcinoma (AGC) of the stomach is associated with poor prognosis due to the lack of effective treatment. Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally AGC in the current multidisciplinary treatment model. Paclitaxel and capecitabine (PX) has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. This phase II study was performed to evaluate the efficacy and safety of neoadjuvant PX chemotherapy in patients with unresectable locally AGC. Methods: Patients with AGC, clinically unresectable because of local invasion and/ or conglomerated regional lymph nodes (station 7, 8, and 9) metastasis on based on laparoscopic staging, were enrolled. PX consisted of paclitaxel 175 mg/m2 i.v. on day 1, and capecitabine 835 mg/m2 twice daily p.o. on days 1–14 every 21 days. After three cycles of NAC, patients with clinically resectable AGC underwent surgical resection. Results: This trial was stopped for poor accrual after 18 patients were enrolled; 50% patients had tumors located in the proximal third of the stomach. Seventeen patients finished three cycles of chemotherapy. The overall response rate was 41.2% (7/17 cases), of which 71.4% (10/14 cases) metabolic response. Fourteen (77.8%) of the 18 patients enrolled underwent surgery, and 12 (85.7%) had an R0 resection. Pathological complete response was observed in one (7.1%) of patients. Toxicity was mild to moderate and there were no treatment-related deaths and no major surgical complications. With a median follow-up of 28.6 months (range 6.4-38.4 months), the 2-year survival rate for all patients was 71.1%. Subgroup analysis found R0 resection (35.7 months vs. 20.6 months, P= 0.005) and patients with pathologic N downstaging (P < 0.001) to have improved overall survival. Conclusions: Neoadjuvant chemotherapy with PX shows promising results in unresectable locally AGC patients without increased morbidity and mortality. Neoadjuvant PX may permit a larger chance of curative resection in unresectable locally AGC patients.

Nail toxicity following systemic chemotherapy is common. Onychopathy during the period of neutropenia following chemotherapy may cause subungual abscesses and serious infection. Despite taxoid-related toxicity being increasingly reported since 2000, there are still phase II systemic chemotherapy studies using taxoid that have never mentioned nail changes. Recently, new criteria for the evaluation of nail toxicity have been suggested. The present report is the first of its kind, in Korea, to describe a case of docetaxel-associated onychopathy, which improved following a reduction in the docetaxel dose.

122 Background: In gastric cancer, platinum and fluorouracil combination chemotherapy (CTx) is commonly used. But the optimal duration of CTx in palliative setting is not known. Thus, we reviewed the pts who rested CTx despite of persistent disease control. Methods: From Mar 2007 to Feb 2012 at Seoul St. Mary’s hospital, we retrospectively reviewed pts as follows; (1) had metastatic or recurrent gastric cancer, (2) received 9 cycles of FOLFOX as 1st-line, (3) had no progressive disease (PD) and rested after completion of 9th cycle. Results: Total 25 pts were reviewed. Median age was 54 (36~77) and 15 pts (60%) were male. 13 pts (52%) had recurrent disease and 12 metastatic initially. All pts were treated with oxaliplatin 100 mg/m2, leucovorin 400 mg/m2 on day 1 and 5-FU 1200 mg/m2 on day 1-2 every 2 weeks. All pts had metastasis; carcinomatosis peritonei (CP, 56%), lymph node (36%), liver (20%) and bone (8%). Nine pts (48%) had non-measurable lesions and 3 no evidence of disease (NED) on CT after palliative surgery. Response evaluation was done every 3 cycles. Among 22 pts with evaluable disease, 5 (20%) showed complete response (CR), 8 (32%) partial response (PR), 2 (8%) stable disease (SD) and 7 (28%) non-CR/non-PD as best response. Median progression free survival (PFS) was 14.2 m (95% CI, 6.6-21.9). The PFS in CP vs. non-CP was 9.9 vs. 21.5 m (log rank P = .037). And PFS according to best response were as follows; 25.5 m in CR + NED group, 15.7 PR, 13.4 non-CR/non-PD and 4.3 SD (log rank P = .014). Other factors did not seem to affect PFS. Conclusions: This study suggested that resting CTx in selected pts would be reasonable in gastric cancer. Especially the presence of CP and the grade of response seemed to be important in patient selection.

Background Platinum agents and oral fluoropyrimidines are widely used in the treatment of advanced gastric cancer. This study was aimed to evaluate the efficacy and safety of two combination regimens (capecitabine plus cisplatin [XP] vs S-1 plus cisplatin [SP]) in patients with untreated recurrent or metastatic gastric cancer. Methods Patients diagnosed as untreated recurrent or metastatic gastric cancer were randomly assigned to either capecitabine (2500 mg/BSA/day; day 1-14) plus cisplatin (60 mg/BSA/day; day 1), every 3 weeks or TS-1 (80-120 mg/day; day 1-14) plus cisplatin (60 mg/BSA/day; day 1), every 3 weeks. Primary end point was overall response rate (ORR), accessed by RECIST criteria (ver. 1.0). The secondary end point was progression free survival (PFS), overall survival (OS), and toxicities. Results 86 patients were anticipated to be enrolled, but 51 patients were randomized to XP (25 patients) arm or SP (26 patients) arm because enrollment was slower than expected. ORR of XP and SP was 52% (13 of 25 assessable patients) vs. 44% (15 of 25 assessable patients), and no significant differences were found (P = 0.778). OS of XP vs. SP was 10.3 months (95% CI; 4.8-15.8) vs. 12 months (95% CI; 9.5-14.5), with no differences (P = 0.785). PFS was 4.6 months (95% CI; 4.6-5.2), 4.4 months (95% CI; 2.2-6.6) each (P = 0.68). The incidence of grade 3-4 neutropenia of XP vs. SP was 40% vs. 43.2%. There were no febrile neutropenia in XP arm, but 7.7% in SP arm. Grade 3-4 thrombocytopenia was 12%, 3.8% each. Other grade 3-4 toxicities were; Nausea (4% vs. 0%), Stomatitis (12% vs. 3.8%), Hand-foot syndrome (16% vs. 0%), Diarrhea (0% vs. 3.8%). Median relative dose intensity of capecitabine vs. TS-1 was 78.7% (range 51.9-116.7%), 87.5% (range 57.1-166.7%). Conclusion There were no significant differences in ORR, OS, and PFS between XP vs. SP arm. The incidence of grade 3-4 neutropenia was similar in both arms, but thrombocytopenia was relatively more common in XP arm. SP was more tolerable than XP in non-hematologic toxicities. Considering the usual dosage of capecitabine in monotherapy is 2500 mg/BSA/day, capecitabine 2500 mg/BSA/day combined with cisplatin 60 mg/BSA may be overdosed, and higher rate of non-hematologic toxicity can be explained. Dosage of capecitabine when combined with cisplatin, needs to be further adjusted for routine use. Disclosure All authors have declared no conflicts of interest.

BACKGROUND: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiotherapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. METHODS: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions. We evaluated the extent of LC3-II, as an autophagosome marker, by Western blotting to measure the hypoxia- or chemotherapy-induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Finally, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed.RESULTS: Compared with normoxia, gemcitabine-induced cell death was significantly decreased under hypoxia, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia. However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4107. doi:1538-7445.AM2012-4107

e13567 Background: CKD 732 is an antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate. Since CKD-732 inhibits angiogenesis which is important to tumor growth and metast...

5120 Background: Platinum based neoadjuvant chemotherapy (NAC) for locally advanced uterine cervix cancer has some benefits to the patients who responded to the chemotherapy, but there is no validated clinical or biologic predictor of response to the chemotherapy. Methods: We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group1 (ERCC1) protein in pretreatment uterine cervical biopsy tissue. 42 patients only stage IIB had been enrolled in the previous etoposide and cisplatin NAC phase II clinical trial, thereby allowing comparison of the effect of cisplatin based NAC on response according to ERCC1 expression. Results: Among 42 patients, ERCC1 was positive in 33 (78.6%) and negative in 9 (21.4%). Response to chemotherapy (by RECIST criteria) was observed in all patients with negative ERCC1 expression. With logistic regression analysis, ERCC1 negatively continued to be an independent predictor for responsiveness of NAC (p = 0.007). Also, regression...

4565 Background: The individual variations in treatment response and the toxicity of combination regimen of oxaliplatin and 5-fluorouracil with leucovorin (FOLFOX) for advanced gastric cancer patients have been reported. The aim of this study is to evaluate the influence of polymorphism of nucleotide excision repair genes that are involved in the metabolism of cisplatin on the clinical outcomes of gastric cancer patients treated with modified FOLFOX-6 chemotherapy. Methods: From March 2006 to December 2007, eighty-two patients with advanced gastric cancer were treated with modified FOLFOX-6 as the primary chemotherapy in our institution. Of these patients, 55 patients who were available for peripheral blood sampling before starting chemotherapy were enrolled in this study. Genomic DNA was extracted from mononuclear cells of patients’ blood. Four polymorphisms were investigated in three genes, ERCC, GSTP and XRCC. Results: The overall response rate (RR) was 40.0%. Median time to progression (TTP) and overall survival (OS) was 6 months (C.I.: 5.0 - 7.0 months) and 15.0 months (C.I.: 9.7 - 20.3 months). Grade 3 or 4 hematologic toxicities were presented in 17 patients (30.9%), gastrointestinal toxicities in 5 patients (9.1%), peripheral neuropathy in 5 patients (9.1%) and hepato-toxicity in 4 patients (7.3%). Most common types of polymorphism were G/G (67.3%) in XRCC1 Arg399Gln, A/A (74.5%) in GSTP1 Ile105Val, C/C (60.0%) in ERCC1 Asn118Asn and C/A (49.1%) in ERCC1 C8092A. The RR was significantly lower in patients with C/C type in ERCC1 C8092A gene than those with other type (25.0% vs 51.6%, p=0.046). However, there were no differences of TTP and OS among the polymorphisms in three genes. The rate of grade 3 or 4 hematologic toxicity was higher in patients with C/T or T/T in ERCC1 codon 118 gene than those with C/C type (45.5% vs 21.2%, p=0.057). Conclusions: We demonstrated that modified FOLFOX-6 chemotherapy was effective and tolerable. The polymorphism of C/C type in ERCC1 C8092A gene was found to be a predictive marker of the poor response and C/C type in ERCC1 Asn118Asn gene was to be a predictive marker of the hematologic toxicity. No significant financial relationships to disclose.

Acute disseminated intravascular coagulation (DIC) associated with gastric cancer is not common and has short survival of 1 to 3 weeks. Systemic chemotherapy in spite of hematologic unstability for gastric cancer may prolong survival time. A 47-year-old woman who complained of dyspnea, vaginal bleeding and easy bruisibility was diagnosed to stage IV gastric cancer with acute disseminated intravascular coagulation based on the laboratory data. She also had multiple bone metastases and bone marrow involvement. This is the first case treated with combination chemotherapy of irinotecan and cisplatin for advanced gastric cancer complicated by disseminated intravascular coagulation at the time of diagnosis, With systemic chemotherapy, some of the bleeding symptoms and the DIC process improved, even not completely recovered. However the patient died of disease progression and survival time was 12 weeks.