bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer
Authors: Ohkawa S. , Amano A. , Ueno M. , Miyakawa K. , Sugimori K. , Tanaka K. , Kida M. 
Published: March 2020

14047 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 and report the results of the phase I trial. Methods: The subjects had unresectable pancreatic ductal cancer. The method of administration was single administration of GEM on the first day of the week from Level 1 to Level 4 at 400 to 1000 mg/m2, with concurrent administration of S-1 at 40 to 100 mg/day × 7 days, repeated every other week as a collaborative trial conducted at 3 facilities. The purpose was to determine the optimal dose with adverse events as an indicator. Results: Eighteen patients were enrolled (3 each at Levels 1, 2, 3 and 4’, 6 at Level 4). Average age was 60.9 years (38 - 71 years). There was no dose limiting toxicity (DLT) up to Level 3. Level 4 was the maximum tolerated dose since DLT was observed in 4/6 patients (mucositis 2, rash 1, anorexia 1), and no DLT was observed in 3 additional patients at Level 4’. The resulting recommended dose was Level 4 (GEM 1000 mg/m2, S-1 100 mg/day). For reference, partial response was observed in 5 patients, and median survival time at this stage is 336±39 days. Conclusions: The recommended dosage of GEM + S-1 combined chemotherapy for unresectable advanced pancreatic cancer was determined in a phase I trial. We intend to proceed to a phase II trial. No significant financial relationships to disclose.
A phase II study of oxaliplatin with biweekly, low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced or metastatic gastric cancer
Authors: Kim H. , Kwon H. , Oh S. Y. , Seo B. G. , Kim S. G. , Kim S. , Kim J. 
Published: March 2020

14052 Background: To determine the activity and toxicities of low dose leucovorin (LV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin every two weeks (modified FOLFOX-4), as a first-line therapy for patients with advanced or recurrent gastric cancer. Methods: Between January 2003 and March 2005, forty-five patients were enrolled in this study. Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at day 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU a 400 mg/m2 bolus and 22 hour continuous infusion of 600 mg/m2 5-FU at day 1–2. This treatment was repeated in 2 week intervals. Results: There was one patient (2.2%) demonstrated a complete response. Twenty patients (44.4%) showed a partial response. Overall response rate was 46.6%. Ten patients (22.2%) showed a stable disease and fourteen patients (31.1%) progressed during the course of the treatment. The median time to progression and overall survival time were 7.73 months (95% CI: 3.6–11.86 months) and 11.17 months (95% CI: 9.06–13.28 months) from the start of the chemotherapy, respectively. A total of 247 cycles were analyzed for toxicity. Major hematologic toxicities included grade 1–2 anemia (39.7%), neutropenia (30.4%), grade 3–4 neutropnenia (10.9%) and thrombocytopenia (9.3%).There were 12 cycles of neutropenic fever. The most common non-hematological toxicities were grade 2 nausea/vomiting (20%), grade 1–2 neuropathy (13.4%) and grade 3 diarrhea (2.2%). There was no treatment related death. Conclusions: The modified FOLFOX-4 regimen is safe and effective regimen as a first line therapy in advanced or metastatic gastric cancer. No significant financial relationships to disclose.
Phase II study of weekly paclitaxel as a second line chemotherapy for metastatic/recurrent gastric carcinoma
Authors: Kodera Y. , Ito S. , Kanyama Y. , Koshikawa K. , Mochizuki Y. , Takase T. , Koike M. , Fujiwara M. , Yamamura Y. , Nakao A. 
Published: March 2020

14059 Background: There is currently no standard treatment for gastric carcinoma patients (pts) who failed initial chemotherapy. Since performance status of these pts deteriorates rapidly, moderate and dose-fractionated single agent regimens have been preferred in Japan in the second line setting. Weekly paclitaxel, one of commonly used regimens in this setting, was explored for the first time in a formal phase II study. Methods: Pts with histologically confirmed gastric carcinoma who had unresectable or recurrent disease with ≥1 measurable lesions per RECIST were eligible. Other eligibility criteria included confirmed progressive disease (PD) per RECIST during a front line chemotherapy, PS ≤2, adequate liver, kidney, and marrow functions, no active gastrointestinal bleeding, and written informed consent. Patients received 80 mg/m2 of paclitaxel weekly for 3 successive weeks with one week of rest. The cycle was repeated until objective disease progression or drug intolerance. Results: 35 pts were enrolled: 29 men and 6 women, age 62 (48∼74), 6 unresectable and 29 recurrent cancers, 13 with poorly differentiated phenotype and 20 with differentiated type, 22 PS0, 8 PS1, and 6 PS2. All front line treatments involved oral fluoropyrimidines and had been S-1 in 29, S-1/CDDP in 5, S-1/CPT-11 in one, and UFT in one patient. One pt declined to continue the treatment due to a Grade 2 taste disturbance after a single dose of paclitaxel, and 34 other pts were evaluable for response. Partial response was observed in 6 pts (response rate 17.6%). Median time to progression was 97 days and median survival time was 214 days (467 days among 22 PS0 patients). The incidence of ≥Grade 3 adverse events were as follows: neutropenia in 7 pts, leucopenia in 5, anemia in 4, anorexia in 4, neurological disorder, nausea, diarrhea, asthenia, and dyspnea in one. Conclusions: Activity of weekly paclitaxel was modest for pts with fluoropyrimidine-refractory gastric carcinoma, but median survival time was satisfactory, with a mild toxicity profile. Further phase II study under less strict eligibility criteria (e.g. inclusion of patients with elevated tumor markers or subjective evidence of clinical deterioration during the front line therapy as the sole indication of disease progression) is underway. No significant financial relationships to disclose.
A phase II study of combination chemotherapy with gemcitabine, 5-fluorouracil, and cisplatin (GFP) for advanced pancreatic cancer
Authors: Kim S. R. , Choi S. B. , Yuh Y. J. 
Published: March 2020

14066 Background: Gemcitabine has been the standard regimen for advanced pancreatic cancer, but the effect on the response rate and survival is still disappointing. 5-fluorouracil(5-FU) and cisplatin are synergistic with gemcitabine as well as with each other. This study is aimed to determine the efficacy and safety of combination chemotherapy with gemcitabine, 5-FU and cisplatin for advanced pancreatic cancer. Methods: Patients(pt) with recurred or advanced pancreatic cancer were entered into this study, who had histologically proven adenocarcinoma, no prior radiotherapy, measurable lesion (≥2cm), ECOG performance scale (PS) 0–2, age 18–70, adequate bone marrow, cardiac and renal function, ALT ≤ 3× normal, and total bilirubin ≤ 2mg/dL.The pt were treated every 3weeks with gemcitabine 800 mg/m2, at 10mg/m2/min on days 1 and 8, 5-FU 1g/m2/24 hour continuous infusion from day 1 through 3 for 72 hours (extended to 4 days later in 12 pt due to lack of toxicity), and cisplatin 60 mg/m2 on day 2, 24 hours after the start of gemcitabine. Concurrent chemo-radiotherapy with gemcitabine 250 mg/m2/week was given to the pt with response of stable disease or better after 4 cycles of chemotherapy, if PS ≤1 and age ≤ 65. Results: Characteristics of 25 eligible pt; 17 male/ 8 female, PS 0,1 in 20 pt, 2 in 4 pt, Stage III in 3 pt, IV in 22, age 40–69 (median 62). Five pt had prior 5-FU-based chemotherapy. A total of 109 cycles were given (median 4; 1–10 cycles/person). Response by WHO criteria: 3 PR (14.3%; 95% confidence interval: 0 - 29.6%), 11 SD (52.4%) and 7 PD in 21 assessable pt. The median time to progression was 230 days (48+-478+) and median survival was 322 days (70+-757+). WHO grade ≥3 toxicity: neutropenia 19.3% (/cycle), thrombocytopenia 28.4%, mucositis 1.8%, and nausea and vomiting 5.6%. The clinical benefit response and correlation of tumor response with CA-19–9 level will be detailed on presentation. Conclusions: The chemotherapy with gemcitabine, 5-FU and cisplatin for advanced pancreatic cancer is safe, active and may have better survival benefit than gemcitabine alone. Based on these results, a nationwide phase III trial comparing with gemcitabine alone has been started. No significant financial relationships to disclose.
Comparison of open and closed techniques of delivery of hyperthermic chemotherapy following cytoreductive surgery in patients with peritoneal carcinomatosis
Authors: Sardi A. , Thillainathan V. , Nieroda C. , Merriman B. , Kostuik P. N. 
Published: March 2020

14067 Background: Intraperitoneal hyperthermic chemotherapy (IPHC) combined with Cytoreductive surgery (CRS) is an effective approach in the management of peritoneal carcinomatosis. A controversy exists concerning the use of an open or closed technique of delivery of the hyperthermic chemotherapy. A retrospective study of a prospective data base was performed to compare these two techniques with respect to overall survival, disease-free survival, length of hospital stay (LOS), and incidence of complications. Methods: From 1998 to 2005, 64 patients underwent CRS and IPHC. Nineteen patients underwent open technique and forty-five underwent closed technique. The pathological diagnoses included appendiceal carcinoma (35), pseudomyxoma peritonei (10), ovarian carcinoma (7), colon carcinoma (6), mesothelioma (5), and sarcoma (1). Cox Proportional-Hazards Regression analysis was performed. Results: Overall 5- year survival and disease free survival was 46% and 22%, respectively. No significant difference in overall survival (p=0.58), disease-free survival (p=0.37), or incidence of complications (p=0.66) was found between the groups. Open technique patients had a significantly shorter LOS than closed with a mean of 8.7 vs. 11.4 days [p=0.01] and a median of 8 vs.11 days [p=0.002] (Kruskal-Wallis Rank Sum Test). Conclusions: The improved survival seen in patients undergoing CRS and IPHC is not dependent on the choice of technique of delivery of the hyperthermic chemotherapy No significant financial relationships to disclose.
A phase II open-label study of cetuximab in unresectable hepatocellular carcinoma
Authors: Gruenwald V. , Wilkens L. , Gebel M. , Wirth T. , Greten T. , Kubicka S. , Manns M. P. , Ganser A. , Malek N. P. 
Published: March 2020

14079 Background: The majority of hepatocellular carcinomas (HCC) express the epidermal growth factor receptor (EGFR). The monoclonal anti-EGFR antibody cetuximab blocks EGFR activation. In the current study, we tested the activity of cetuximab in this disease. Methods: Pts with advanced or metastatic HCC and measurable disease with adequate renal, hematologic and hepatic function (bilirubin <2×UNL; AST/ALT <3×UNL) were eligible. Prior regional or systemic therapy was permitted. A total of 15 pts have been enrolled to date. Primary endpoint: rate of progression free survival (PFS) at 24 weeks of treatment. Secondary endpoints: overall survival (OS), objective response rate (ORR), tolerability and identification of surrogate markers. Tumor biopsies were performed prior to treatment, after 4 wks and at time of progression. Specimens were analyzed for genetic instability (FISH analyses) and cell cycle regulation (p27Kip1, skp2, EGFR) by immunohistochemistry. Cetuximab was administered 400 mg/m2 iv week 1, and 250 mg/m2 weekly thereafter until disease progression. Demographics: male 14, female 1, age 46–78 yrs (median 65), cirrhosis 13/15 pts, liver transplantion 2/15pts, Childs-Pugh class A: 14/15, B:1/15; distant metastases 6/15; risk factors: hepatitis C virus (HCV) 2/15, HBV 1/15. Contrast enhanced ultrasound examinations were performed on all pts at −2, 4, and at the time of progression to evaluate tumor blood flow. Results: At the time of the first tumor evaluation (8 wks) 2/15 pts (13%) achieved stable disease (SD). Tumor specimens showed a significant increase in copy numbers for centromeric probes against chromosome 1 and 8 in patients with progressive disease. Toxicity: all pts developed skin rash: Grade (Gr) 1 in 12/15 pts, Gr 2 in 3/15. Allergic reaction Gr 1 was seen in 1 pt. 2 pts required dose reduction for drug-related toxicity Conclusions: Cetuximab is well tolerated in pts HCC and liver cirrhosis, without additional toxicity. To date only modest activity has been detected in these unfavorably advanced pts. Accrual will continue to 35 pts total. At time of disease progression tumor specimens showed chromosomal instability with an increase in copy numbers of chr. 1 and 8. Updated results will be presented at the meeting. [Table: see text]
Oxaliplatin combined with leucovorin plus 5-FU (FOLFOX) in patients with advanced/metastatic biliary tract carcinoma
Authors: Lim J. Y. , Cho J. Y. , Paik Y. H. , Lee S. J. , Won J. Y. , Kim J. H. , Yoon D. S. , Lee D. K. 
Published: March 2020

14093 Background: Biliary tract carcinoma is often diagnosed at advanced stage, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A phase II trial was conducted to study a FOLFOX regimen as first- or second- line therapy in biliary tract carcinoma. Methods: Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients were between 18 and 75 years of age and had histologically confirmed, measurable adenocarcinoma. Patients were stratified according to prior chemotherapy(6) and no prior chemotherapy(15). Treatment consisted of intravenous oxaliplatin (100mg/m2) as a 2 hours infusion on day 1 followed by leucovorin 100mg/m2 on day1 and 5-FU 1000∼1200mg/m2 as a 24 hours infusion on day 1,2. Treatment was repeated every 3 weeks for up to 6 cycles. Tumor response, survival and safety were determined Results: A total of 21 patients were evaluable;12 men and 9 women with a median age of 57(range 37–71). Tumor sites were: intrahepatic (n=7) and extrahepatic biliary duct (n=9); gallbladder (n=4); and ampulla (n=1). Total 115 cycles were administered (median 5 cycles, range 2∼12). According to RECIST criteria, partial response 3(14.3%), stable disease 10(47.7%) and disease progression.8(38%). The overall response rate with and without prior chemotherapy were 0%(0/6) and 20%(3/15), respectively. In patients without prior chemotherapy (15), median progression-free-survival and overall survival were 6.6(range, 1.2∼12.8) and 8.7(range, 3.7∼19.3) months. Grade 1–2 neurotoxicity, fatigue, diarrhea, anorexia, nausea were common. Grade 3 neutropenia and thrombocytopenia occurred in 23% and 4.7% of the patients respectively. There was no treatment related death. Conclusions: FOLFOX should be considered an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma. No significant financial relationships to disclose.
First line chemotherapy with FOLFOX 4 in elderly patients (>65 years) with advanced or metastatic gastric cancer (A/MGC): A pilot study
Authors: Azzarello D. , Giuffrè C. , Panuccio V. , Giannicola R. , Del Medico P. , Zavettieri M. , Raffaele M. , Maisano R. , Falzea A. , Nardi M. 
Published: March 2020

14095 Background: Cisplatin/5-FU based regimens are considered therapies of choice for the treatment of A/MGC even if severe toxicities are reported especially in elderly pts. FOLFOX 4 regimen is standard chemotherapy in adjuvant and metastatic colorectal cancer and it is effective and well tolerated also in elderly population. Several trials have showed activity and safety of FOLFOX regimen in A/MGC. For these reasons, we carried out this pilot study in order to evaluate the feasibility of FOLFOX 4 in elderly pts (>65 yrs) with A/MGC. Methods: From June 2003 to June 2005 we treated with FOLFOX 4 regimen 31 pts with median age of 70 yrs (range 66–79), 20 males and 11 females, ECOG PS 0–2 with MGC in 19 cases and AGC in 12 cases. All pts had measurable disease according to RECIST criteria, NCI-CTC was employed to grade toxicity except for neurotoxicity graded by specific scale. Results: We recorded 4 CR (13%), 6 PR (19%), 9 SD (29%) and 12 PD for an ORR 32% and median TTP of 6.8 months. A total of 281 courses were delivered with a median of 8 courses (range 4–15) per pt. No toxic deaths occurred and no therapy has been ended for toxicity or pt refusal. Pts did not receive G-CSF support. 43 courses were delayed for toxicity (maximum 2 weeks). Haematological adverse events were: 23 episodes of neutropenia G1/2, 8 episodes of G3 and 3 episodes of G4 neutropenia; G1/2 thrombocytopenia occurred in 15 episodes; anemia G1/2 was reported in 13 episodes. Besides, we recorded 12 episodes of emesis G2 and 2 episodes of G3; 24 episodes of G1/2 and 7 episodes of G3 oral mucositis were recorded; diarrhoea G1/2 was a common event (around 50% of cycles) while severe diarrhoea was a rare. Alopecia G1/2 was registered in 19 pts, G1neurosensorial toxicity (specific scale) occurred in 16 pts, G2 in 7 pts and G3 in one pt. One pt had hypersensitivity reaction at first infusion that did not occurred anyone by prolonged infusion of L-OHP. Conclusions: Our data show that FOLFOX 4 is active in the treatment of A/MGC and that toxicity profile is favourable in elderly population in comparison to standard regimens. No significant financial relationships to disclose.
Treatment outcomes with first and second line chemotherapy in advanced and metastatic pancreatic cancer patients
Authors: Mancuso A. , Saletti P. , Sacchetta S. , Romagnani E. , Cavalli F. , Sternberg C. N. 
Published: March 2020

14107 Background: Recent advances in the treatment of pancreatic cancer might influence the management of locally advanced and metastatic disease, nonetheless prognosis remains dismal (1-year survival rates: 24%). The impact on survival of palliative second-line therapy is hotly debated. Methods: We retrospectively reviewed the clinical records of 103 pancreatic cancer patients admitted to San Camillo/Forlanini Hospital (Rome, Italy) and the Oncology Institute of Southern Switzerland during the period June, 1997 to August, 2005 [60 males, 43 females, median age 65 years (range 43–80); median ECOG performance status (PS): 1]. All patients received Gemcitabine as single agent (90%) or in combination with Oxaliplatin (10%) as upfront therapy. A total of 12 fluoropyrimidine-based salvage regimens were administered to 46 patients in the second line setting. Best supportive care was selected in 57 patients after failing first line therapy. Results: Of 103 evaluable patients, first line chemotherapy produced overall tumor growth control of partial response (PR) and stable disease(SD) by RECIST criteria of 52.4% with a median progression free survival (PFS) of 4.6 months. Multivariate analysis revealed that the most important prognostic factor for PFS was the patient’s PS, as patients with PS of 1–2 at diagnosis had significantly worse results than patients with PS = 0 (First line PFS: 110 days vs 193 days, p<0.05). Baseline CA19–9 and number of metastatic sites were not independent prognostic factors for better first-line PFS. PR was observed in 8/46 patients (17.3%) who received second line chemotherapy, SD in 10 (21.7%), and 28 patients progressed (61%). Median overall second line PFS was 3.2 months. Patients who had responded to first-line Gemcitabine were more likely to respond or attain stable disease with second-line treatment, with a PFS of 5.6 vs 2.85 months (p<0.05). The overall survival for all evaluable patients was 8.4 months. 1-year survival was 52% for patients treated with second line therapy. Conclusions: These results are consistent with historical studies and suggest that fluoropyrimidine-based salvage regimens have marginal but definite activity and should be considered in patients who have responded to first line chemotherapy with an optimal PS. No significant financial relationships to disclose.
Weekly high-dose 5-FU as 24h-infusion and folinic acid (AIO regimen) plus Irinotecan in patients with advanced non-resectable adenocarcinoma or squamous epithelial carcinoma of the oesophagus: Interim analysis of a phase II trial
Authors: Boxberger F. , Wolff K. , Brueckl V. , Brueckl W. M. , Meier C. , Maennlein G. , Horbach T. , Hohenberger W. , Hahn E. G. , Wein A. 
Published: March 2020

14109 Background: At the moment of establishing the diagnosis, in approximately 50–60% of the patients with esophageal carcinoma only palliative treatment is possible due to either a locally advanced tumour growth or due to distant metastases. While adenocarcinomas of the esophagogastric junction are increasingly treated like gastric carcinomas, no palliative standard regimen is established for advanced squamous carcinomas of the oesophagus. The question should be answered whether the AIO regimen plus Irinotecan may achieve similarly positive results in esophageal carcinomas as in gastric carcinomas. Methods: Prospective phase II trial, patients: n=20, trial start: 03/2003, chemotherapeutic regimen: Irinotecan (80 mg/m2 i.v. as 1h-infusion; d 1, 8, 15, 22, 29, 36, qd 57) as well as folinic acid (500 mg/m2 i.v.) together with 5-Fluorouracil (2000 mg/m2 i.v.; d 1, 8, 15, 22, 29, 36, qd 57) as 24h-infusion via port catheter. Results: n=16 (adenocarcinomas: n=8, squamous epithelial carcinomas: n=8); median age: 59,3 (44–72) years; men/women: 13/3; ECOG 0/1/2: 4/11/1; chemotherapeutic applications: 314. Evaluable in terms of toxicity: n=16. Higher grade toxicity: grade III diarrhea: n=2, grade III hyponatremia: n=1, thrombosis of the vena subclavia: n=1, grade III stomatitis: n=1, ischemic lesion of the brain stem: n=1. Two patients died after 2 chemotherapeutic applications with known peritoneal carcinomatosis and high tumour burden. Evaluable in terms of response: n=13. PR: n=7 (54%), SD: n=4 (31%), PD: n=2 (15%). Conclusion: The AIO regimen plus Irinotecan is excellently manageable on an outpatient basis in a multimorbid patient group and shows high efficacy in both adenocarcinomas and squamous epithelial carcinomas of the oesophagus. Final results, however, particularly in terms of median survival, still remain to be seen. No significant financial relationships to disclose.