bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxaliplatin, irinotecan, and cetuximab in advanced gastric cancer. First efficacy results of a multicenter phase II trial (AGMT Gastric-2) of the Arbeitsgemeinschaft Medikamentoese Tumortherapie (AGMT)
Authors: Woell E. , Greil R. , Eisterer W. , Fridrik M. , Grünberger B. , Zabernigg A. , Mayrbäurl B. , Russ G. , Thaler J. 
Published: August 2020

4538 Background: Patients (pts.) suffering from advanced gastric cancer have still a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1) we could show that the combination of oxaliplatin and irinotecan was well tolerated and showed an objective response rate of 58% (Anticancer Res 28:2901–2906, 2008). This chemotherapy regimen was tested in combination with cetuximab in a multicenter phase II trial. Methods: Oxaliplatin 85 mg/m2 biweekly and irinotecan 125 mg/m2 biweekly were combined with cetuximab 400 mg/m2 loading dose and subsequently weekly 250 mg/m2. 51 patients with histological proven unresectable and/or metastatic gastric adenocarcinoma were treated in a first line setting. Median age: 62 years (range 19–79 years), PS 0: 25 patients, PS 1+2 26 patients, single metastatic site: 24 patients, multiple metastases: 27 patients. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 and included neutropenia (35% of pts.), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3 and 4 toxicities included neutropenia in 9/1 pts., thrombocytopenia in 1/0 pts., anemia in 3/1 pts., nausea in 2/0 pts., and diarrhea in 7/2 pts. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of pts., in 7 pts. grade 3 neurotoxicity was observed. Acneiform skin rash grade 1 / 2 / 3 / 4 was reported in 31% / 20% / 6% / 2% of pts. respectively. 16 pts. went off-study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), progressive disease (n=3), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). 35 patients are assessable for response with 1 pt. (3%) showing a CR, 21 pts. (60%) a PR, 7 pts. (20%) a SD and PD in 6 pts. (17%). A disease control rate was achieved in 83%. Median time to progression was 24.8 weeks (n=29), median overall survival 38.1 weeks (n=32). Conclusions: The combination of oxaliplatin and irinotecan with cetuximab is feasible, safe and active in advanced gastric cancer. [Table: see text]
Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer: A randomized phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: Thuss-Patience P. C. , Kretzschmar A. , Deist T. , Hinke A. , Bichev D. , Lebedinzew B. , Schumacher G. , Gebauer B. , Maier V. , Reichardt P. 
Published: August 2020

4540 Background: Up to now the value of 2nd-line therapy for metastatic gastric cancer is unclear. So far there are no randomized phase III data comparing 2nd-line chemotherapy to BSC. Irinotecan has proven activity in 1st-line therapy. In this randomized phase III study we compared irinotecan to BSC to evaluate the value of 2nd- line chemotherapy for gastric cancer. Methods: Prospective multicenter randomized phase III study, open label. Eligibility: Metastatic or locally advanced gastro-esophageal junction or gastric adenocarcinoma. Objective tumor progession (PD) within 6 months after 1st- line chemotherapy. ECOG PS 0–2. Statistics: Primary endpoint: Overall survival (OS). Hypothesis: H1: OS(Irinotecan)>OS(BSC). Calculated number of pts needed (power 80%, alpha error 5%): 60 pts per arm. Stratification for a) PD less versus (vs) more than 3 months after 1st line chemotherapy, b) ECOG PS 0/1 vs 2. Treatment: Arm A: Irinotecan 250mg/m2 q3w (1st cycle) to be increased to 350 mg/m2, depending on toxicity. Arm B: BSC Results: Between Oct 2002 and Dec 2006 40 pts were randomized. The study was closed prematurely due to poor accrual. Arm A:21 pts, arm B 19 pts. Median age A: 58 yrs (43–73), B: 55 yrs (35–72); PD less vs more than 3 months after 1st-line chemotherapy: A: 18 / 3, B: 17 / 2pts. ECOG PS 0/1 vs 2: A: 17/ 4, B: 14/ 5pts. Pre-treatment with cisplatin: A: 21, B:19 pts. Arm A: 68 cycles administered in 21 pts. Toxicity: (main CTC grade 3/ 4): Nausea 1 pt, vomiting 1 pt, diarrhoea: 5 pts, neutropenic fever: 2 pts, data incomplete 6 pts. In 37% of 19 evaluable pts irinotecan dose was escalated to 350mg/m2. Response (19 pts evaluable): No objective responses, SD 58%, PD 42%. Improvement of tumor related symptoms: 44% of pts in arm A, 5% in arm B. Survival: (evaluable pts arm A 21, arm B 18): median survival arm A: 123 days (95%CI 95–216), arm B 72.5 days (95%CI 41–106); OS: HR=2.85 (95%CI 1.41–5.79), Logrank test (two-sided): p=0.0027. Conclusions: To our knowledge this is the first randomized phase III study investigating 2nd- line chemotherapy in gastric cancer. Irinotecan as 2nd-line chemotherapy significantly prolongs overall survival compared to BSC. 2nd-line chemotherapy can now be considered as a proven option in gastric cancer. [Table: see text]
Second-line chemotherapy with FOLFIRI in patients with metastatic gastric cancer (MGC) not previously treated with fluoropyrimidines
Authors: Di Lauro L. , Fattoruso S. I. , Giacinti L. , Vici P. , Sergi D. , Lopez M. 
Published: August 2020

4549 Background: No established second-line chemotherapy exists for patients (pts) with MGC failing to respond or progressing after first-line chemotherapy. This study was designed to determine the efficacy and safety of FOLFIRI combination used as second-line therapy in pts with MGC not previously treated with regimens containing fluoropyrimidines. Methods: Pts with measurable distant metastases, previously treated with a combination of epirubicin, docetaxel and cisplatin or oxaliplatin as first-line therapy, received irinotecan 180 mg/mq (150 mg/mq in pts >70 ys old) as a 1-h infusion day 1; leucovorin 100 mg/mq/day followed by bolus fluorouracil (FU) 400 mg/mq and a 22-h infusion of FU 600 mg/mq day 1–2, every 2 weeks for a maximum of 12 cycles or until disease progression, unacceptable toxicity or patients refusal. Endpoints were response rate (RR), time to progression (TTP), overall survival (OS) and safety. Results: 38 pts were enrolled: M/F 23/15; median age 66 ys (34–75); median ECOG PS 1 (0–2); number of metastatic sites 1/2/≥3: 9/18/11 pts, respectively. A total of 223 cycles was performed (median 6, range 2–12). One CR and 8 PR were observed for an overall RR of 24% (95% CI, 11–39 %). Disease remained stable in 11 pts. Median TTP was 4.0 months (95% CI, 2.9–5.1) and median OS was 6.2 months (95% CI, 4.7–7.7). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 29%, 3% and 8% of pts, respectively. Febrile neutropenia was seen in 2 pts (5%). Other grade 3 toxicities included diarrhea in 5 pts (13%), mucositis in 2 pts (5%) and vomiting in 2 pts (5%). There were no treatment related deaths. Conclusions: FOLFIRI is an active and well tolerated second-line regimen for MGC pts not previously treated with fluoropyrimidines. No significant financial relationships to disclose.
Meta-analyses of randomized trials assessing the influence of chemotherapy and prognostic factor in advanced/recurrent gastric cancer
Authors: Pozzo C. , Ohashi Y. ,   on behalf of the GASTRIC project
Published: August 2020

4550 Background: Advanced or recurrent stomach cancer remains an incurable disease. Several drugs and different combinations of chemotherapy have been investigated but very often with small sample sizes making definitive conclusions difficult. The GASTRIC project is an individual-patient-data (IPD) based meta-analysis in the advanced disease setting to quantify the potential benefit of various chemotherapies. We used this large database to study the role of various prognostic factors and potential interactions with chemotherapy. Methods: All randomized clinical trials (RCT) closed to patient accrual at the end of 2004 were eligible. Radiotherapy, intraperitoneal chemotherapy, or immunotherapy was excluded. The primary endpoint was overall survival (OS). Baseline variables included sex, age, performance status (PS), diseases status at entry, prior surgery, number of organs involved at entry, location of metastasis, TNM stages, histology, operative procedures, and geographic area. The hazard ratio (HR) and 95% confidence interval (CI) was calculated by the multivariate Cox analysis to assess of the prognostic factors for their relationship to OS. Results: Fourty-nine eligible RCTs (7,120 patients) were identified. As of December 2008, IPD from 21 trials (3,619 patients) with a median follow- up of 7.3 months were available for OS. There was no statistically significant difference between 5FU-based, anthracycline-based, platinum-based, taxane-based, or irinotecan-based regimens versus any other CT. In the multivariate Cox regression analysis stratified by trial and treatment arm, PS of 2 (HR, 2.43; 95%CI, 2.02 to 2.94) compared to PS of 0, metastatic (HR, 1.29; 95%CI, 1.01 to 1.64) compared to local advanced, many number of organs, and location of metastasis (especially with peritorium; HR, 1.75; 95%CI, 1.23 to 2.48) compared to none were strongly associated with lower survival. Conclusions: Our interim results could not show an overall survival benefit in favour of 5FU-, anthracycline-, platinum-, taxane-, or irinotecan-based regimens compared with a regimen without the specific chemotherapy. We confirm the impact of PS, diseases status at entry, number of organs involved, and location of metastasis on OS. No significant financial relationships to disclose.
Phase II study of S-1 monotherapy in taxane, cisplatin refractory gastric cancer
Authors: Cho S. , Lee S. , Hwang J. , Bae W. , Shim H. , Park C. , Park M. , Chung I. 
Published: August 2020

4551 Background: S-1 is a fourth-generation oral fluoropyrimidine that was developed to mimic protracted continuous infusion of 5-fluorouracil (5-FU). In previous study, S-1 demonstrated promising activity which is comparable to combination chemotherapy in advanced gastric cancer. This phase II study evaluated the efficacy and safety of S-1 salvage chemotherapy, in patients with taxane and cisplatin refractory gastric cancer. The primary end point was progression free survival and secondary end points were overall survival, safety and clinical benefit. Methods: Patients were eligible if they had histologically documented gastric adenocarcinoma previously treated with taxane (docetaxel or paclitaxel) and cisplatin; age≥18; Eastern Clinical Oncology Group (ECOG) performance status of 2 or less; adequate organ function; no evidence of gastrointestinal obstruction or passage disturbance. S-1 treatment was performed according to BSA as followed; < BSA 1.25, 80 mg/day, 1.25 ≤ BSA < 1.5, 100 mg/day; BSA ≥ 1.5, 120 mg/day. Every dosage was delivered divided two times and administered for 4 weeks followed by 2 weeks of resting period. Treatment continued until progression of disease or life-threatening adverse events were occurred. Results: Fifty-four patients were enrolled in this study and of the patients, forty-eight patients were evaluable. A total 194 chemotherapy cycles were administered and median number of cycles was three. Four (8.3%) patients had a partial response and 18 (37.5%) patients had stable disease. The median progression free survival and overall survival were 3.8 and 10.2 months, respectively. Grade III/IV hematologic toxicities included neutropenia in 6 patients (12.5%) and there was no febrile neutropenia. Most of nonhematologic toxicities were diarrhea, asthenia, and mucositis, and there was no grade 3 or grade 4 except two patients, who developed grade 3 anorexia and diarrhea, respectively. The clinical benefit response was observed in 16 patients (33.3%). Conclusions: This results showed that S-1 monotherapy was active and safe salvage chemotherapy in patients with advanced gastric cancer previously treated with taxane and cisplatin. No significant financial relationships to disclose.
Preoperative cetuximab and radiation (XRT) for patients (pts) with surgically resectable esophageal and gastroesophageal junction (GEJ) carcinomas: A pilot study from the Hoosier Oncology Group and the University of Texas Southwestern
Authors: Agarwala A. K. , Hanna N. , McCollum A. , Bechar N. , DiMaio M. , Yu M. , Tong Y. , Becerra C. R. , Choy H. 
Published: August 2020

4557 Background: Pre-operative chemoradiotherapy (CRT) followed by surgical resection is a standard treatment option for pts with resectable esophageal or GE junction (GEJ) carcinomas (CA). Cetuximab, when combined with XRT is effective treatment for locally advanced cancers of the head and neck. We conducted this study to evaluate this regimen in pts with esophageal and GEJ CA. Methods: This is a single arm, open label pilot study combining cetuximab with XRT for pts with resectable esophageal and GEJ CA. The primary objective is to determine the pathologic complete response rate (pCR) (null hypothesis: p=0.20; alternative hypothesis: p=0.35) and determine the feasibility and toxicity of this regimen when given prior to esophagectomy. Key eligibility criteria are: squamous cell (SC)or adenoCA of the esophagus or GEJ, ECOG PS 0–2, clinical stage II -IVa, and eligible for esophagectomy. Pts received a loading dose of cetuximab at 400mg/m2 2 weeks prior to XRT, then weekly at 250 mg/m2 starting one week prior to XRT until completion of 50.4 Gy XRT. After satisfactory recovery, pts had esophagectomy. Results: Patient characteristics (n=40): median age 65 years (range, 54–82); 92% male; PS 0/1 63%/32%; esophageal/GEJ 65%/35%; adenoCA/SC 78%/22%; 36 pts have completed cetuximab and radiation and 26 pts have undergone esophagectomy. Of the 26 pts that have undergone esophagectomy, 13 obtained a pCR. 5/13 SC had pCR and 8/13 adenoCA had pCR. 10 pts did not undergo surgery for various reasons including disease progression (n=7), AE unrelated to treatment (n=2), and personal decision to forgo esophagectomy (n=1). 4 patients are still completing cetuximab/XRT. The most common G3 adverse event was rash (56%). Other G3 toxicities were infrequent and included dysphagia (6%), infection (6%), and GI bleed (3%). There have been no treatment or surgery related deaths. Conclusions: Cetuximab and XRT results in pCR's in pts with esophageal and GEJ CA (rate of pCR 13/36), including patients with either SC or adenoCA histologies. G3/4 toxicities, including dysphagia were generally uncommon. Further study of this combination prior to esophagectomy is warranted. [Table: see text]
Metastatic gastroesophageal cancer and long-term survival
Authors: Power D. G. , Jhawer M. , Feilchenfeldt J. W. , Kelsen D. P. , Shah M. A. 
Published: August 2020

4560 Background: Despite modest therapeutic improvements, resistance to systemic chemotherapy develops in most pts with advanced gastric/GEJ (GE) adenocarcinoma. Median OS rarely exceeds 10 mo. However, a subgroup of pts(5–10%) have substantial benefit from chemotherapy, living >2 years. We describe clinicopathological characteristics of a large cohort of long term survivors(LTS) with metastatic GE adenocarcinoma. Methods: Our institutional database of pts with GE adenocarcinoma who received chemotherapy between 1999–2008 identified 103 pts with metastatic disease (M1) surviving >2 years from M1. We evaluated clinicopathologic characteristics for correlation of LTS with chemotherapy. Results: From Jan 1999–2008, 1,140 pts with metastatic GE cancer received systemic therapy. Male:female 1.9:1 and median age 66 yrs(22–89). From the time of M1, 103 pts (9%) lived >2 yrs. Of this cohort, median follow up is 51 mo and median OS from M1 is 33 mo (24–106 mo); 44 pts remain alive (43%), 9 pts ≥5 yrs. Demographics: M:F 1.8:1, median age 61 yrs (22–84). Tumors were located at GEJ/cardia (n=52), body/fundus (n=29), antrum/pylorus (n=22), and were mainly poorly differentiated (n=61). Laurens subtype was reported in 33 cases (17=diffuse, 15=intestinal). 77 pts presented with M1 and 26 developed recurrence after resection. Sites of M1 are: peritoneum(35), single visceral organ(19), M1 lymph nodes (24), >1 site (25). 52 pts received 2–3 treatment regimens, range 1–7. Common regimens were docetaxel/fluoropyrimidine (26), cisplatin/irinotecan (21), and DCF (11); intraperitoneal chemotherapy (5). Surgery was performed in 28 pts, 26 gastrectomies (15 with occult peritoneal M1, 11 once peritoneal M1 cleared) and 2 metastatectomies; 7 pts received RT(6 to primary, 1 to M1 site). No distinct clinicopathologic correlates were identified as associated with prolonged survival with systemic chemotherapy. Conclusions: Although systemic chemotherapy has modestly improved survival in advanced GE cancers, long term control is possible. The lack of clinicopathologic correlates for LTS suggests that molecular/genomic characteristics may distinguish LTS and predict chemo-sensitivity. We are now exploring tumor and normal tissue from LTS versus matched controls (survival <1 year) for molecular/genomic correlates for LTS No significant financial relationships to disclose.
Lymph node ratio and survival for gastric cancer: A retrospective analysis of the SEER database
Authors: Shridhar R. , Dombi G. W. 
Published: August 2020

4561 Purpose: To determine the prognostic significance of the lymph node ratio (ratio of number of positive lymph nodes to number of dissected lymph nodes) in gastric cancer patients. Methods: We retrospectively analyzed 10,176 gastric patients from 1990–2003 who underwent curative gastrectomy from the SEER database. Survival curves were calculated according to the Kaplan-Meier method and analyzed with log-rank test. Multivariate analysis of prognostic factors related to survival was performed by the Cox proportional hazard model. Results: The lymph node ratio (LNR) was a strong predictor of survival. LNR was equally predictive of survival whether the analysis was restricted to patients with <15 lymph nodes dissected or >15 lymph nodes dissected. Survival of patients with a LNR of 0.1–5% was not significantly different than node negative patients; however, survival of patients with a LNR of 5–10% was significantly different than node negative patients. Multivariate analysis showed that LNR, T-stage, tumor size, and number of lymph nodes positive were independent prognostic predictors of death and that LNR was the strongest predictor for death. Multivariate analysis showed that the number of lymph nodes dissected was an independent prognostic factor for survival. Moreover, LNR was an independent prognostic factor for N1 and N2 patients by AJCC staging. LNR trended toward significance in AJCC N3 patients. Conclusions: LNR was the strongest predictor of death in gastric cancer patients when compared to T-stage, number of lymph nodes positive, and tumor size. LNR is equally predictive regardless of the adequacy of the lymph node dissection. No significant financial relationships to disclose.
Stemness signature of BMI1 and clinical outcome in esophageal cancer patients undergoing neoadjuvant chemoradiotherapy
Authors: Fujiwara Y. , Yoshikawa R. , Tao L. , Tsujimura T. , Sasako M. 
Published: August 2020

4572 Background: The polycomb group (PcG) family BMI1, acting downstream of the hedgehog (Hh) pathway, plays an essential role in the self-renewal of hematopoietic, neural, and intestinal stem cells, and is dysregulated in many types of cancer. Our recent report has demonstrated that Gli-1 nuclear expression indicative of Hh signalling activation can predict very poorer prognosis of esophageal squamous cell carcinomas (ESCCs)(Br J Cancer 2008). As data were not available on the clinical role of BMI1 expression, we analyzed whether it could be also used to predict disease progression and prognosis in ESCC patients undergoing neoadjuvant chemoradiotherapy (CRT). Methods: BMI1, Gli-1, and p16INK4A expressions were evaluated in 78 ESCC patients by immunohistochemical staining. All patients underwent preoperative chemoradiotherapy; 40 Gy irradiation plus FP (5- FU and CDDP) regimen. Results: In total, 24 out of 78 patients (30.8%) showed BMI1 positive expression. All Gli- 1 nuclear positive cancers expressed BMI1. There was no significant correlation between p16INK4A expression and BMI1 expression. Overall survival (OS) was significantly correlated with the absence of BMI1 expression. The patients with BMI1-positive cancers showed significantly poorer prognoses than those without (mean disease-free survival (DFS) time 16.8 vs 71.2 months, P<0.005; mean OS time 21.8 vs 76.6 months, P<0.001). Conclusions: We demonstrated that BMI1 expression indicative of PcG protein chromatin silencing pathway activation was significantly correlated with esophageal cancer recurrence and poor prognosis after CRT, and that it was not inversely correlated with the presence of the downstream target p16INK4A. These findings suggest that the stemness signature including components of Hh and PcG pathways might be involved in promoting cancer regrowth and progression after CRT, and is thus a potential prognostic biomarker and rational therapeutic target for attacking the “more aggressive” cancer cells causing recurrence. No significant financial relationships to disclose.
Phase II trial of preoperative bevacizumab (Bev), irinotecan (I), cisplatin (C), and radiation (RT) in esophageal adenocarcinoma: Preliminary safety analysis
Authors: Ilson D. , Bains M. , Rizk N. , Rusch V. , Flores R. , Park B. , Shah M. , Kelsen D. , Miron B. , Goodman K. 
Published: August 2020

4573 Background: Preo chemoRT with weekly I/C and 5040 cGy followed by surgery is well tolerated [JCO 24: Abstract 4032; 2006]. ECOG trial E1201recently reported a median survival of 34 months with this preop regimen [JCO 26: Abstract 4532; 2008]. Bev + chemo improves response rate (RR) and time to progression (TTP) when added to weekly I/C in advanced esophagogastric cancer but does not increase chemo toxicity [JCO 24: 5201; 2006]. We are now combining in a Phase II trial Bev/I/C with concurrent radiotherapy (RT) in esophageal adenocarcinoma (EA) with the primary endpoint of safety. Methods: Patients (pts) with resectable Siewert's I or II EA were staged by EUS, PET, and CT. Induction chemo consisted of I-50–65 mg/m2 and C-30 mg/m2 weeks 1,2,4,5, Bev-7.5 mg/kg weeks 1 and 4; and, during RT (180 cGy daily to 5040 cGy), I/C was given weeks 7,8,10,11 and Bev weeks 7,10. Esophagectomy was 6–8 weeks after RT. A planned toxicity analysis was made in 10–15 pts completing chemoRT, and in 10 pts undergoing surgery: toxicity was acceptable if grade 3 / 4 hematologic toxicity remained < 72% and non hematologic toxicity < 40% during combined chemoRT (based on our prior phase II trial of I/C/RT [JCO 24: Abstract 4032; 2006]); and if pts undergoing surgery had no surgical complication related to Bev. Results: 18 pts have been enrolled, 12 male: 6 female; 7 Siewert I: 11 Siewert II; T3N1 12: T3N0 5: T2N0 1. 14 are evaluable for toxicity, 2 are too early, one progressed prior to RT, and one was taken off due to a CVA from a patent foramen ovale. Grade 3/4 neutropenia occurred in 4 pts (29%). Grade 3/4 non heme toxicity occurred in 5 pts (36%), including esophagitis 2 pts (14%), neutropenic fever 1 pt (7%), and pulmonary embolism 1 pt (7%). No grade 3 / 4 hypertension was seen, and 3 pts (21%) developed grade 1 proteinuria. Ten pts underwent surgery, and there were no unexpected surgical or wound complications; there were 2 anastomotic leaks. Pathologic responses: 1 pathologic CR and 1 T0N1. Conclusions: In a preliminary analysis of pts treated with Bev + preop chemoRT in EA, there was no increase in hematologic/non hematologic toxicity or Bev related surgical complications. Accrual will continue to 33 patients. Supported by Genentech. [Table: see text]