bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of S-1 in patients with gemcitabine resistant advanced pancreatic carcinoma
Authors: Sudo K. , Yamaguchi T. , Ishihara T. , Nakamura K. , Saisho H. 
Published: March 2020

14070 Background: S-1 is an oral fluoropyrimidine derivative with reported response rate of 21.1∼37.5% for advanced pancreatic carcinoma (Ueno, Oncology 2005; Furuse, ASCO 2005). The primary objective of this study was to assess the efficacy and safety of S-1 in patients with gemcitabine resistant advanced pancreatic carcinoma. Methods: Patients with histologically or cytologically proven, metastatic pancreatic carcinoma who had failed prior chemotherapy with gemcitabine were eligible for this study. Other eligibility criteria included an ECOG performance status (PS) of 2 or less; an age of at least 20 years; adequate organ function; and written informed consent. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 28 days, followed by a 14-day rest period. Treatment was repeated every 6 weeks until disease progression. Results: Seventeen patients were enrolled with the following characteristics: median age 67 (range 40–75); male/female = 9/8; ECOG PS 0/1/2 = 1/8/8. All patients were included in analysis. Treatment was generally well tolerated and no life threatening toxicity was observed. Grade 3–4 toxicities were anorexia (17.6%) and fatigue (5.9%). Common grade 1–2 toxicities were anorexia (35.3%), anemia (35.3%), leukocytopenia (29.4%) and diarrhea (23.5%). Three patients were discontinued S-1 because of toxicities. Out of the 17 eligible patients, 3 patients (17.6%) achieved a partial response and 5 patients (29.4%) had stable disease. A marked decrease (≥50%) in tumor markers was observed in 5 (29.4%) of the patients. (CA 19–9 in 3 patients, CEA in 1 patient, DUPAN-2 in 1 patient) The median progression-free survival and the median survival time from the date of initiation of S-1 were 4.1 months (95% CI, 2.0 to 6.2 months) and 5.7 months (95% CI, 2.6 to 8.7 months), respectively. Conclusions: S-1 is well tolerated and active in patients with gemcitabine resistant advanced pancreatic carcinoma. Further investigation of this treatment appears warranted. No significant financial relationships to disclose.
RP101 improves the efficacy of gemcitabine in treating pancreatic carcinoma
Authors: Haenel M. , Quietzsch D. , Heinemann V. , Boeck S. , Schmid R. M. , Liebert A. , Fahrig R. 
Published: March 2020

14075 Background: (E)-5-(2-bromovinyl)-2’-deoxyuridine (BVDU, RP101), was initially tested in a phase 1 pilot study in pancreatic cancer. Patients (n=13) received gemcitabine (1000 mg/m2), cisplatin (50 mg/m2) and RP101 (500 mg/day). The median survival was 447 days and the TTP was 280 days. Ten of the 13 pts lived longer than one year, 4 nearly two years. Based on these promising results a phase 2 study was initiated to explore varying doses of RP101 used with a fixed dose of GEM. Methods: Pts with advanced pancreatic adenocarcinoma were eligible for treatment in this single arm study. 22 pts (16 stage IV and 5 stage III) received GEM 1000 mg/m2 on days 1, 8 and 15 of a 28-day schedule. RP101 treatment, at doses of 500, 625, 750, 875 or 1000 mg/day, was on the same day and for three days after chemotherapy. The mean age was 60 years and 73% of pts were males. Results: The results are based on interim data from an ongoing study and patients at the 2 highest dose groups are still being treated. All RP101 dose groups were combined for analyses, which included all enrolled pts. The data on the 6-month survival status show that 41% are alive; 23% dead; and 36% followed less than 6 months. The median survival (95% CI) is 7.1 months (5.9, not calculated) and 14/22 pts (64%) are still alive. The 6 month survival rate (95% CI) is 0.69 (0.52, 0.85). This compares very favorably with a large recent randomized trial in which pts who received GEM alone had a median survival (95%CI) of 5.9 months (5.1–6.7). PFS and TTP continue to be assessed in this ongoing trial. There appears to be a dose dependent increase in peak GEM levels as a function of the dose of RP101. To date, adverse events are consistent with those observed with GEM or the underlying disease. Conclusion: RP101 may improve treatment of advanced pancreatic cancer when used with gemcitabine. Updated data on survival, PFS, and safety will be presented based on available data. [Table: see text]
Irofulven (IROF) combined with oxaliplatin (OXA) in advanced hepatocellular carcinoma (HCC) patients (pts): Phase I study (preliminary results)
Authors: Goldwasser F. , Houédé N. , Bertheault-Cvitkovic F. , Misset J. , Raymond E. , Benettaib B. , Kahatt C. , MacDonald J. R. , Weems G. 
Published: March 2020

14082 Background: IROF, a semisynthetic derivative of the natural product illudin S, is a novel DNA binding agent that has demonstrated antitumor activity in pts with a variety of chemoresistant tumors. Currently available systemic chemotherapy offers limited benefit to HCC pts. Evidence of IROF activity in HCC was seen with IROF 11 mg/m2 daily x4 every 28 days (Stuart et al, ASCO 2003), and every other week dosing schedules (Falcon et al, ASCO 2004). Preclinically, IROF exhibits additive and synergistic antitumor activity in combination with OXA. Methods: Dose escalation was performed in pts with HCC and other advanced malignancies in this Phase I study. Dose levels (DL) were OXA (mg/m2)/IROF (mg/kg): DLI: 40/0.3; DLII: 40/0.4; DLIII: 50/0.4; DLIV: 60/0.4; DLV: 70/0.4; DLVI: 80/0.4. OXA (2-hour infusion) was followed by IROF (30-min infusion) on Days 1 and 15 every 28 days. Results: Of the 41 pts treated, 8 had HCC, 2 treated at DLI and 6 at DLVI. Median age of these 8 pts was 48 years; PS (ECOG) 0/1: 1/7; median AFP 1253 ug/L (range 16–39760); 3 pts had a history of hepatitis (B/C : 2/1) and 2 of cirrhosis; 3 had prior chemotherapy and 3 chemoembolization; all but one had metastatic disease. Safety: A median of 3 cycles was given (range 1+ to 5+). One pt experienced grade (G) 3 vomiting, 5 pts G1–2 asthenia and nausea, 4 G3 thrombocytopenia and 3 G3 neutropenia. Efficacy: Activity was seen in 6 of the 8 HCC pts, (DLI: 1; DLVI: 5); 1 confirmed PR with AFP decrease from 1250 to 1.9 (99.8%; DLVI) and PFS of 3.5+ months; 1 PR, non-confirmed (42% AFP decrease, 20741 to 11974; DLVI) with PFS of 3.6 months, and 4 SD (DLI: 1; DLVI: 3) were observed with a median duration of 3.6 months (3.2–6.0 +); 3 SD pts (3.8, 3.9 and 3.2+ month duration) had 12%, 52% and 36% AFP decrease respectively. Based on activity in the whole cohort and in the absence of an MTD, DLVI (80/0.4) was selected as the recommended dose. Conclusions: Combined IROF/OXA shows substantial activity and is well tolerated in advanced HCC pts. Additional HCC patients will be included at the RD to evaluate the efficacy of IROF/OXA in this indication. [Table: see text]
Cetuximab plus gemcitabine/oxaliplatin (GEMOX) for patients with unresectable/recurrent intrahepatic cholangiocarcinoma refractory to GEMOX
Authors: Paule B. , Bralet M. , Herelle M. , Rage E. , Ducreux M. , Guettier C. , Adam R. 
Published: March 2020

14084 Background: Gemcitabine-oxaliplatin (GEMOX) is active and well tolerated in advanced biliary tract adenocarcinomas. We report a single institution retrospective study on using cetuximab plus GEMOX in patients with intrahepatic cholangiocarcinoma that expresses Epidermal Growth Factor Receptor (EGFR) and who have progressed on first line chemotherapy (GEMOX). Methods: 9 patients (5 females, 4 males, mean age: 54 years, range: 27–74, performance status: 0–1) with a recurrent or unresectable intrahepatic cholangiocarcinoma (peripheral n=6, hilar n=3, histologically proven) resistant to GEMOX received cetuximab 400 mg/m2 on day 1 then 250mg/m2 weekly, in combination with gemcitabine 1,000 mg/m2 as a 10 mg/m2/min infusion on day 1 and oxaliplatin 85mg/m2 as a 4-h infusion on day 2, every 3 weeks. EGFR expression was determined by immunohistochemistry (n=9) and EGFR gene copy number on tumour cells was detected by fluorescent in situ hybridization (FISH) (n=8). Tumor response was measured using standard RECIST criteria. Results: EGFR was detected by immunohistochemistry (9/9) in more than 10% tumour cells without gene amplification (8/8). A total of 57 cycles were given (range: 3–11 per patient). Median duration follow-up was 7 months (range: 6–12). At 3 months, 3/9 had partial response, 3/9 stable disease and 3/9 a progression disease. At 6 months, CT scan showed 1 complete response, 1 partial response, 1 stable disease and 6 progression diseases. The median time to tumour progression was 6 months, with a median duration of response of 3 months (range: 2–8). Five patients died. Of the 4 patients who are still alive, the mean duration follow-up is 11 months (range: 10–14). There was no treatment related death, no anemia, no neurotoxicity. One grade 3 neutropenia was noted and acne-like rash was observed in 7/9 patients. The median survival from time of initiation of treatment was 10 months. Conclusions: Even if there is no amplification of EGFR gene, Cetuximab plus GEMOX is well tolerated and provides good palliative effects in advanced cholangiocarcinoma. A prospective phase II trial with GEMOX with and without cetuximab is being planned to assess the real impact of cetuximab in unresectable cholangiocarcinoma expressing EGFR. No significant financial relationships to disclose.
A phase II of high dose capecitabine plus irinotecan for patients with advanced or metastatic gastric cancer: preliminary results
Authors: Oh S. , Seo H. , Sung H. , Choi I. , Kim S. , Kim S. , Seo J. , Kim B. , Shin S. , Kim Y. , Kim J. 
Published: March 2020

14086 Background: Capecitabine is the prodrug of 5-FU to generate maximal tumor activity in tumor site and/or improve the tolerability, has demonstrated the synergistic activity with irinotecan in some solid cancers . Previous study showed the dose intensification of capecitabine increased the response rate with comparable toxicities in metastatic colorectal cancer. We conducted this study to ascertain the efficacy and toxicity of irinotecan and high dose capecitabine combination chemotherapy for chemotherapy-naïve advanced or metastatic gastric cancer. Methods: Patients who were advanced or metastatic gastric cancer and have not received any chemotherapeutic drug except adjuvant chemotherapy, received irinotecan 130mg/m2 intravenously (i.v) for 90 min on day 1 and day 15 and capecitabine 3500 mg/day, divided two, was administered for 7 consecutive days from day1 and day 15, and this was followed by a 7-day drug-free interval. Results: 35 eligible patients were enrolled in this study from Nov/2003 to Nov/2006. 14 women and 21 men: median age 51 ys, range 27–81. A total 106 courses were administered, and median number of courses per patient was three (range, 1–8). Intent-to-treatment analysis showed the one complete response (2.9%), 13 partial responses (37.1%), 9 stable disease (25.7%), 8 progressive disease (22.9%) and 4 non-evaluable patients (11.4%). The overall response rate was 40% (95% CI: 23.5–56.5). Grade 3–4 toxicities were: neutropenia 8 (22.8%), nausea/vomiting 2 (5.7%), stomatitis 1 (2.9%), ischemic colitis 1 (2.9%), anemia 3 (8.6%), diarrhea 2 (5.7%), alopecia 3 (8.6%). Treatment related death was shown at one patient due to pneumonia. Dose intensity of irinotecan and capecitabine was 94% and 93%, respectively. Median time to progression was 4 months (range, 0.5 - 11 months), median survival duration was 8.5 months (range, 0.5 - 45 months), and median response duration was 2.5 months (range, 0.5 - 9 months). Conclusions: We suggest that irinotecan and high dose capecitabine combination chemotherapy is the tolerable regimen to advanced or metastastic gastric cancer with promising activity. No significant financial relationships to disclose.
Capcitabine and oxaliplatin (XELOX) in the treatment of advanced gastric cancer
Authors: Quek R. , Lim W. T. , Foo K. F. , Koo W. H. , Toh H. C. 
Published: March 2020

14089 Background: Effective 1st line chemotherapy that is easily delivered and tolerable is important in patients with advanced gastric cancer (AGC). This study aimed to evaluate the toxicity and efficacy of combination capecitabine and oxaliplatin (XELOX), given 3 weekly, in patients with AGC. Methods: Twenty-seven patients with AGC, were treated with XELOX at the National Cancer Centre Singapore between June 2003 and December 2005. Capecitabine was given 2000 mg/m2/day, days 1–14, and oxaliplatin was given 130 mg/m2 on day 1, every 21 days. Results: The median age was 61 years with 22% of patients ≥ 70 years. One-third of patients had ECOG 2 - 4, and 33% of patients had signet ring cell histology. Median doses of capecitabine and oxaliplatin achieved were 1500 mg/m2/day (1200 - 2400) and 130mg/m2 (80 - 130) respectively. A median of 5 cycles (range 1 - 8) of XELOX was administered. All 27 patients had toxicity assessment. Toxicities were infrequent and mild. There were 3 cases of grade 3/4 toxicities (thrombocytopenia, neutropenia and fatigue). Twenty-two patients had measurable disease for response evaluation. Complete (CR) and partial (PR) response rates were 9 and 50% respectively. Overall response rate was 59%. Chemo-naïve patients had better responses (80% vs 25%). Four of the remaining 5 patients had reduction in non-measurable disease or in tumor marker levels. Of the 9 patients with ECOG > 1, there was radiological CR in 1 patient and 5 PR; 1 had normalization of CEA, another reversal of disseminated intravascular coagulation and the third decreased ascites. The median time to progression and overall survival were 5.9 months and 7.6 months respectively. Conclusions: XELOX regimen is safe, active and well tolerated in AGC even in patients with poor ECOG status. It is easily administered without requiring a central venous catheter. This regimen should be investigated further in a prospective manner. No significant financial relationships to disclose.
Phase II study of cetuximab in patients with unresectable or metastatic hepatocellular carcinoma
Authors: Zhu A. X. , Blaszkowsky L. , Enzinger P. C. , Bhargava P. , Ryan D. P. , Meyerhardt J. , Horgan K. , Hale K. , Sheehan S. , Stuart K. 
Published: March 2020

14096 Background: Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis with no established systemic treatment regimen. Epidermal growth factor receptor/human epidermal growth factor receptor 1 (EGFR/HER1) and ligand expression is frequently seen in HCC. Recent studies suggest that erlotinib, an EGFR/HER1 tyrosine kinase inhibitor, may have benefit in stabilizing HCC. We performed a phase II study with cetuximab, a chimeric monoclonal antibody that binds selectively to EGFR, in advanced HCC. Methods: Eligibility criteria include unresectable or metastatic measurable HCC, up to two prior systemic regimens, performance status ≤ 2, CLIP score ≤ 3, and adequate organ functions. The initial dose of cetuximab is 400 mg/m2 intravenously (IV) administered over 120 minutes, followed by weekly infusions at 250 mg/m2 IV over 60 minutes. Each cycle is defined as 6 consecutive weekly treatments. EGFR expression was assayed by immunohistochemistry and trough serum concentrations of cetuximab were determined during the first cycle. The primary endpoint of the study was progression free survival (PFS). Results: The planned 30 patients have been enrolled: median age = 58 (33–82), M/F = 23/7, ECOG 0/1/2 = 16/12/2, CLIP 0/1/2/3=2/9/14/5. No responses were seen. Five patients had stable disease. The median number of cycles on study per patient was 1 (range, 1–3). 16 patients developed progressive disease following one cycle of treatment. Only one patient remains on study. The median PFS and OS were 41 days (95% CI, 36 to 79) and 157 days (95% CI, 112 to not available), respectively. The treatment was generally well tolerated. No treatment related deaths occurred. Treatment related grade 1–2 toxicities included rash (83%), fatigue (47%), hypomagnesemia (27%), nausea (20%), anemia (13%), diarrhea (13%), anorexia (13%), and elevation of SGOT/SGPT (10%). Grade 3 SGOT, hypomagnesemia, and fever without neutropenia were seen in one patient (3%) each. Conclusions: Cetuximab has no activity in HCC in this phase II study. It can be safely given with tolerable toxicity profiles in HCC patients. Updated information on toxicity, efficacy, EGFR expression and pharmacokinetics will be presented at the meeting. Supported by Bristol-Myers Squibb. [Table: see text]
Arsenic trioxide in patients with hepatocellular carcinoma: A phase II trial
Authors: Lin C. , Hsu C. , Hsu C. , Hsu W. , Cheng A. , Yang C. 
Published: March 2020

14129 Background: Arsenic trioxide induces growth inhibition and apoptosis in human hepatocellular carcinoma (HCC) cell lines. A phase II trial was conducted to evaluate the efficacy and toxicity of single-agent arsenic trioxide in patients with HCC. Methods: Inclusion criteria included advanced HCC patients to whom no standard palliative treatment can be offered, good organ function and liver function reserve. Patients received arsenic trioxide 0.16–0.24 mg/kg/day for 5–6 days per week for 3–4 weeks followed by one-week rest. Tumor response was accessed every 2 months. Primary endpoint was percentage of patients with 6-month disease stabilization. Results: Twenty-nine patients (M/F = 24:5; median age: 59) with locally advanced or metastatic HCC received a total of 61 cycles (median, 2; range, 1–6). One patient had partial remission. Three patients had disease stabilization for at least six months. The 6-month tumor stabilization rate was 14% (95% CI, 1–27). The median overall survival was 4.8 months (95% CI, 1.4–8.2) and one-year survival estimated by Kaplan-Meier methodology was 30%. Conclusions: Single-agent arsenic trioxide using this dose schedule is not active against advanced HCC patients. No significant financial relationships to disclose.
Bicarbonate-treated gastroendoscopy
Authors: Kim Y. 
Published: March 2020

14138 Background: Endoscopy is the most powerful examination to detect cancer. We showed efficacy and feasibility of the bicarbonate(bC)-treated gastroendoscopy (bCGE) to the patients (Y. Kim, et al. ICACT2004, Paris, France, and Y. Kim. 2006 GI Cancers Symposium, San Francisco, CA, USA). We tried an alternative preparation, divided alkalization, to modify the bCGE to less threaten patients in the examination. Methods: Enrollment-criteria was described; age 20 to 85, Performance Status 0 to 2, and no history of lidocaine (L) allergy, no wound in the oral cavity, and no severe organ dysfunction. The alkalizing-agent was 7-% sodium-bC solution (S-bC). The divided bC-treatment was shown: gurgling and swallowing a half, 10-mL, of 20-mL S-bC divided by L application into two parts, the 1st and the 2nd alkalization. pH Levels in the left pharyngeal-arch were measured. The patients were applied a deffervescent agent orally, L sprays in the pharyngeal-arch and L gel onto the pharyngeal-wall for 5-minute, and gastrointestinal-paralyzing agents intramuscularly. The reflexes (coughing and nausea), and pulse rates (PR) of the patients were monitored in the bCGE. Results: This study analyzed 9-patient in intent-to-treat method. All patients, 100%, accomplished the bCGE with the divided alkalization. Course of pH Levels, incidence of the reflexes and increasing ratio of PR were given in the table below. The divided alkalization enhanced the L effects in the pH Levels after the 2nd alkalization depending manner. Conclusions: We found the bCGE with the divided alkalization might be effective and feasible. The pH Levels after the 2nd alkalization could be the predictive factors for the successful bCGE with the divided alkalization. [Table: see text] No significant financial relationships to disclose.
Poorly differentiated neuroendocrine carcinoma-small cell of the gastrointestinal tract. Institutional experience
Authors: O′connor J. M. , Sade J. P. , Pairola A. , Domenichini E. , Cabanne A. , Marmisole F. , Mendez G. , Bestani C. , Chacón M. , Roca E. 
Published: March 2020

14142 Background: PDNEC-Small cell (OMS Clasification, grade III)of the GI tract are rare diseases. Small cel represent 0,1% to 1% of all GI malignancies, and are included in the group of PDNEC but: Do these group behave biologically and respond to treatment in the same way? Trying to elucidate this matter, we performed a retrospective analysis of our group of pts. with PDNEC. Methods: A database search was done. from 1997 to 2005 we found 31 pts. with PDNEC/Small cell from the GI Tract treated in our Centers. A review of the clinical records was performed with special interest in response rate and overall survival. interest. Results: 14 pts. were informed by the pathologist at diagnosis PDNEC and 17 pts. as small cell. Median age: 50 years (r 19–84). The most common primary site was Esophagus-Stomach (29%), followed by pancreas 9 pts. (29%. 9 pts.(29%) presented with metastatic disease with unknown orimary Sistemic symptoms were common. A majority of our pts. (61%) presented with overt metastases. The liver was involved in 14 pts. (61%) follow by lymph nodes in 5 (16%). The most common chemotherapy used was a combination Platinum based. Overall response rate was 43%. TTP for all pts were 7 months (95% IC 0.34–0.69). Overall survival was 12 months (95% IC 0,31–0,70). We observed differences in term of overall survival and TTP in favor of PDNEC (15 months vs 10 months and 8 vs 4 months respectively) pNS. Conclusions: PDNEC-Small cell had bad prognosis. In our Serie we found differences between both groups, although not statiscally significant (due to a low number of patients). Definitive data of treatment for the management of this group of pts. still lacks. No significant financial relationships to disclose.
Response to the combination of thalidomide and capecitabine as second-line therapy in pancreatic carcinoma after treatment and failure with gemcitabine
Authors: Beganovic S. , Loesh D. 
Published: March 2020

14150 Background: A literature search shows only one published case report utilizing the combination of thalidomide and capecitabine as second-line therapy in adenocarcinoma of the pancreas. We report two patients with pancreatic carcinoma treated as second-line therapy with this combination. Methods: CASE #1: Fifty five-year-old female with metastatic pancreatic carcinoma demonstrated clear evidence of progression after 8 months of treatment with gemcitabine At this time, she was started on thalidomide 50 mg at bedtime every other night with capecitabine 1500 mg p.o. b.i.d. for two weeks with one week off. After eight weeks of this regimen, the patient had clinical response with a decrease in abdominal pain, improvement in performance status, and a decrease in her CA 19–9 from 1154 units/mL to 101 units/mL. With this treatment the patient was fully ambulatory and without symptoms for 7 months. CASE #2: The patient is 55-year-old male treated with adjuvant radiation therapy and chemotherapy after surgical resection of his adenocarcinoma of the pancreas. Eight months later, he developed hepatic metastasis and was treated with gemcitabine with progression of disease on that agent. Palliative treatment with capecitabine 1500 mg p.o. b.i.d. for two weeks and one week off was instituted with thalidomide 50 mg at bedtime every other day. After four months of this regimen, the patient had a clinical response with no abdominal pain and decrease in his CA 19–9 from 4647 units/mL to 55 units/mL. Ten months after initiation this regimen patient is asymptomatic, working full time and continues to take thalidomide and capecitabine. Conclusions: Response to second line therapy in adenocarcionoma of pancreas is rare. We are reporting two cases of second-line therapy of adenocarcinoma of the pancreas treated with the combination of thalidomide and capecitabine. Decline in CA 19–9, duration of response, and improvement in functional patient status were unexpected findings. Use of combination of capecitabine and thalidomide in the treatment of the pancreatic adenocarcinoma should be evaluated further in clinical trials. No significant financial relationships to disclose.