bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cetuximab, paclitaxel, carboplatin and radiation for esophageal and gastric cancer
Authors: Suntharalingam M. , Dipetrillo T. , Akerman P. , Wanebo H. , Daly B. , Doyle L. A. , Krasna M. J. , Kennedy T. , Safran H. 
Published: March 2020

4029 Background: Cetuximab is an IgG1, chimerized, monoclonal antibody that binds specifically to the epidermal growth factor receptor. Cetuximab improves survival when combined with radiation for patients with locally advanced head and neck cancer. We evaluated the safety and efficacy of the addition of cetuximab to concurrent chemoradiation for patients with esophageal and gastric cancer. Methods: Patients with adenocarcinoma or squamous cell cancer of the esophagus or stomach without distant organ metastases were eligible. Patients with locally advanced disease from mediastinal, celiac, portal and gastric lymphadenopathy were eligible. Surgical resection was not required. Clinical complete response was defined as no tumor on postreatment endoscopic biopsy. Patients received cetuximab, 400mg/m2 week #1 then 250 mg/m2/week for 5 weeks, paclitaxel, 50 mg/m2/week, and carboplatin, AUC =2 weekly for 6 weeks, with concurrent 50.4 Gy radiation. Results: Thirty-seven patients have been entered. The median age was 61 (range of 30–87). Thirty-four have esophageal cancer and 3 have gastric cancer. Of the patients with esophageal cancer, twenty-five have adenocarcinoma and nine have squamous cell cancer. Thus far, 30 patients have completed treatment and are evaluable for toxicity. There have been no grade 4 non-hematologic toxicities and 1 pt had grade 4 neutropenia (3%). Six patients (20%) had grade 3 esophagitis. Other grade 3 toxicities included dehydration (n=5), rash (n=9), and paclitaxel/cetuximab hypersensitivity reactions (n=2). Eighteen of 27 patients (67%) have had clinical complete response. Seven pts out of 16 (43%) who have gone to surgery have had a pathologic CR. Conclusions: Cetuximab can be safely administered with chemoradiation for patients with esophageal cancer. Consistent with the data in head and neck cancer, cetuximab increases cutaneous toxicity but does not increase mucositis/esophagitis when combined with chemoradiation. Further evaluation is ongoing. [Table: see text]
Neoadjuvant chemotherapy improves outcomes of chemoradiation therapy for locally advanced pancreatic cancer
Authors: Rana V. , Krishnan S. , Abbruzzese J. L. , Xiong H. Q. , Varadhachary G. R. , Ho L. , Janjan N. A. , Evans D. B. , Wolff R. A. , Crane C. H. 
Published: March 2020

4036 Background: Two-thirds of all pancreatic cancer patients have radiographically detectable metastatic disease at the time of diagnosis. Most of the remaining patients have locally advanced, unresectable disease that is typically treated with either chemoradiation or chemotherapy alone. We explored the possible benefit of the use of consolidative chemoradiation after induction chemotherapy. Methods: Between December 1993 and October 2005, 318 patients with locally advanced, non-metastatic, pancreatic cancer were treated at our institution with concurrent chemoradiation therapy. All patients underwent CT staging and biopsy confirmed adenocarcinoma. 245 patients received chemoradiation (CR) as initial treatment while 73 patients received a median of 2.5 months of induction chemotherapy prior to chemoradiation (CCR). Radiosensitizers included 5FU (42%), gemcitabine (39%) and capecitabine (19%) and most patients (88%) received 30 Gy of radiation therapy. The most common induction chemotherapy regimens were gemcitabine and cisplatin (73%) and gemcitabine alone (15%). Results: All statistics are actuarial and calculated from date of initial treatment. Median follow-up was 5.5 months (range 1–63 months). For all patients, overall survival was 9.0 months and 2-year survival was 8%. Age, gender, histology, grade, radiation fractionation and concurrent chemotherapy regimen had no impact on outcomes on univariate analysis. However, overall survival was 8.5 months in the CR group and 11.9 months in the CCR group (p = 0.0004). Median time to local progression was 6.0 months in the CR group and 8.4 in the CCR group (p = 0.0055). Median time to distant progression was 5.8 months in the CR group and 9.5 months in the CCR group (p=0.0136). Conclusions: In one of the largest series of locally advanced pancreatic cancer patients, the use of induction chemotherapy followed by chemoradiation seems to prolong median survival over initial treatment with chemoradiation. By excluding patients who progress rapidly during induction chemotherapy, this approach presumably selects patients most likely to benefit from a local treatment modality. This strategy merits prospective evaluation. [Table: see text]
Phase II study of RAD001 (everolimus) and depot octreotide (Sandostatin LAR) in patients with advanced low grade neuroendocrine carcinoma (LGNET)
Authors: Yao J. C. , Phan A. T. , Chang D. Z. , Jacobs C. , Mares J. E. , Rashid A. , Meric-Bernstam F. 
Published: March 2020

4042 Background: Effective systemic therapy for advanced LGNET is lacking. Patients with mutation in TSC2, an endogenous inhibitor of mTOR develop LGNET. mTOR also mediate signaling downstream of IGF1 and VEGF, pathways important in LGNET. RAD001 inhibits the serine-threonine kinase activity of mTOR. Octreotide may have cytostatic activity and has been described to inhibit VEGF and IGF1 production in solid tumors. Methods: Treatment consisted of depot octreotide 30 mg IM q28 days, and RAD001 5 or 10 mg po daily. Response evaluation is performed every 12 weeks. Results: 32 patients (18 carcinoids, 13 islet cell) were enrolled between 2/05 - 1/06. 20 had prior octreotide. 27 patients have completed 12 weeks of therapy at the 5 mg dose level and undergone response evaluation. By RECIST criteria, response rate was 15%. There were 4 PR, 19 SD (including 4 patients having 18–28% reduction), 4 PD. PR occurred in 2 carcinoids, and 2 islet cell. PFS rate at week 24 was 71%. Of 21 patients with radiological progression prior to study entry, 17 have completed 12 weeks of therapy. Among these, there were 3 PR, 10 SD, 4 PD. Of 18 patients with elevated chromogranin A at baseline, 9 (50%) patients had > 50% reduction. Treatment is generally well tolerated. The most common toxicity is mild aphthous ulceration. CTC G3/4 toxicity include: anemia (1), thrombocytopenia (1), leukopenia (1), fatigue (3), aphthous ulcer (2), diarrhea (2), hypoglycemia (2), pain (2), rash (2), hyperglycemia (1), edema (1), nausea (1). Conclusions: RAD001 5 mg po daily is well tolerated in combination with Depot Octreotide. Anti-tumor activity has been observed. An additional cohort will be treated at RAD001 10 mg daily dose. Optional blood draws and tumor biopsies will be performed to help assess biomarkers that may predict benefit. No significant financial relationships to disclose.
Preoperative chemotherapy followed by resection vs. surgery alone for locally advanced esophageal carcinoma: Interim analysis of a randomized study
Authors: Stilidi I. , Bokhyan V. , Tryakin A. , Suleymanov E. , Kononets P. , Malikhova O. , Tjulandin S. 
Published: March 2020

4055 Background: Outcome of the patients (pts) with locally advanced esophageal cancer is poor. A prospective trial was undertaken to investigate whether preoperative chemotherapy (CT) followed by surgery results in increase of disease free survival (DFS) in pts with locally advanced resectable thoracic esophageal cancer. Methods: Previously untreated pts with stage T3–4N0–1M0, T1–2N1M0 resectable esophageal cancer were eligible for the study. After clinical evaluation (incl. chest CT-scan, endosonography) they were randomized into CT (two cycles of FLEP: cisplatin 80 mg/m2, day 1; etoposide 80 mg/m2 d 1–3, leucovorine 20 mg/m2 and 5-fluorouracil 425 mg/m2, bolus, days 1–3; every 21 days) followed by surgical resection (Ch-S group), or resection alone (S group). Four weeks after completion of CT pts underwent transthoracic extended 2 or 3-field esophagectomy with intrapleural esophago-gastrostomy through I. Lewis approach. Results: From March 2001 to September 2005 78 pts (Ch-S group, n=38; S group, n=40) were treated in our center. Median f.-up for survived pts was 20 (range, 3–53) months. All pts but one had squamous cell carcinoma. Pts’ characteristics (tumor stage and histology, coexisting disorders, age and gender) were well balanced between the two treatment groups. Main toxicity of CT was hematological, with neutropenia gr. 4 was observed in 7 (18%) pts. There was no other serious toxicity as well as preoperative toxic deaths. Complete response was observed in 3 (7,9%) pts, partial response in 23 (60,5%) pts, progression of disease in 3 (7,9%) pts of Ch-S group. Rate of R0 resection was higher in Ch-S group (86,8%) compared with S group (65%, p=0,03). There was no difference in postoperative mortality between both groups. 3-year DFS was 58,3% vs. 27,7% (p=0,01) and 3-year overall survival was 62,9% vs. 39,8% (p=0,08) in Ch-S and S groups, respectively. Conclusions: Two cycles of preoperative CT improve DFS in pts with resectable locally advanced thoracic esophageal cancer. Accrual is continuing. No significant financial relationships to disclose.
Phase II trial of preoperative irinotecan-cisplatin (IC) followed by concurrent IC and radiotherapy (IC/RT) for locally advanced gastric and esophago-gastric junction adenocarcinoma (LA-G/EGJ-A)
Authors: Vega-Villegas M. E. , Galán-Guzmán M. C. , Gallego-Plazas J. , Cervantes A. , Escudero P. , Tabernero J. , Massutí B. , Alonso-Orduña V. , Asensio D. , Rivera F. 
Published: March 2020

4059 Background: Long-term survival for LA-G/EGJ-A is poor and could be improved by preoperative chemoradiotherapy. We performed a phase II trial to evaluate IC followed by IC/RT in this setting. Methods: Patients with locally advanced (stage II-IV, M0) G/EGJ-A were included. Main objective was pathological complete response (pCR). Secondary objectives were toxicity, response to preoperative treatment and resection rate. Pretreatment staging included an esophagogram, EUS and CT scan. Two courses of IC (Irinotecan 65mg/m2 and Cisplatin 30mg/m2 d 1 and 8, each 21 d) were given and pts without progression received IC/RT: daily RT (180cGy fractions, total dose: 5040cGy) with concurrent IC (Irinotecan 65mg/m2 and Cisplatin 30mg/m2 d 1, 8, 15 and 22 of RT). Response to preoperative treatment was evaluated with EUS and CT scan 3–4 weeks after the end of radiotherapy. Five to 8 weeks after RT, surgical resection was performed if feasible. Results: Between 2003 and 2005, 40 pts were included: 32 men; median age 65 (45–80); PS (ECOG): 0: 38%, 1: 59%, 2: 3%; Location and resectability: Esophago-gastric Junction: 16 pts (resectable: 11 pts), Stomach: 24 pts (resectable: 13 pts); Stage: II: 13 pts, III: 15 pts, IV: 12 pts. Grade 3–4 toxicity of IC (40 pts evaluable): neutropenia 22 % (febrile 5%), diarrhoea 8%, emesis 5%, asthenia 3%. One pt (3%) died during IC due to progression. All the 33 pts who received IC/RT were evaluable for toxicity (G-3–4): neutropenia 39% (febrile 0%), diarrhoea 0%, emesis 6%, asthenia 26%, thrombocytopenia 6%. Four pts (12%) died during IC/RT (toxicity: 2 pts, progression: 2 pts). Response to preoperative treatment: PR: 6 pts, SD: 21 pts, Prog: 6 pts, No Evaluated: 7 pts. R0 resections were performed in 12 out of 24 (50%) initially resectable pts (pCR: 2 pts) and in 4 out of 16 (25%) initially non-resectable pts (pCR: 0 pts). One pt died during the first 30 days after resection. With a median follow-up of 12 months, 16 pts (40%) are alive with disease, 10 (25%) pts are alive and disease free and 14 pts (35%) have died. Conclusions: Preoperative IC> IC/RT obtained moderate response and resection rates with mild toxicity in LA-G/EGJ-A. Supported by a grant from Prasfarma/Almirall Prodesfarma. [Table: see text]
Capecitabine and docetaxel for advanced gastric cancer
Authors: Thuss-Patience P. C. , Kretzschmar A. , Dogan Y. , Blau I. , Pink D. , Lebedinzew B. , Micheel S. , Dörken B. , Reichardt P. 
Published: March 2020

4068 Background: Docetaxel is increasingly integrated into chemotherapy combination regimens against gastric cancer. Docetaxel and 5-FU were compared to ECF and appeared to be very active and well tolerated (Thuss-Patience et. al. JCO 2005). In the current study the dual combination capecitabine and docetaxel (CapDoc) is evaluated to develop a convenient out-patient regimen with minimal toxicity. Methods: Prospective multicenter phase II trial. Eligibility: Metastatic or locally advanced gastro-esophageal junction or gastric adenocarcinoma, ECOG PS 0–2, no prior palliative chemotherapy. Chemotherapy: Docetaxel 75 mg/m2 d1, capecitabine 2000 mg/m2 d1–14, q3w. For part I of the study (presented here) accrual is completed (40 pts). In part II we reduced the starting dose of docetaxel to 60 mg/m2 and capecitabine to 1600 mg/m2 to further improve tolerability (accrual ongoing, 8 pts included so far, presented at meeting). Results: 40 pts are included in this trial (part I). Age: 32–79 years (median 61), M/F 29/11, ECOG PS 0: 7 pts, 1: 27 pts, 2: 6 pts. Number of organs involved by metastases: 1: 9 pts, 2: 11 pts, 3: 16 pts, more than 3: 4 pts. Measurable disease (RECIST): 40 pts. 233 cycles of chemotherapy are administered so far. Toxicity: 40 pts are evaluable for toxicity (worst grade per patient; % of pts): Grade 1/2/3/4: Nausea: 53/10/3/- %, vomiting: 18/13/-/3 %, diarrhea: 23/20/13/- %, asthenia: 38/40/10/- %, stomatitis: 23/15/10/- %, alopecia: 25/53/-/- %, fever not neutropenic: 10/20/3/- %, neutropenic fever: -/-/10/3 %, nail changes: 33/28/-/- %, paresthesia: 18/18/5/- %, dizziness: 15/8/5/- %, hand-foot-syndrome: 25/18/18/- %, leuko-neutropenia: 8/13/25/28 %, thrombocytopenia: 18/-/-/- %, anemia: 40/15/5/- %, fluid retention: 13/5/-/-, pulmonary embolism or thrombosis: 3/5/3/5. Dose adjustments of docetaxel had to be made in 45% and of capecitabine in 55% of pts. Response: 26 of 37 pts with tumor related symptoms showed a subjective improvement of symptoms (70.3%). 38 pts are evaluable for objective response: CR 1 pt (2.6%), PR 20 pts (52.6%), NC 14 pts (36.8%), PD 3 pts (7.9%), (objective response rate: 55.3%). Median time to tumor progression 5.5 months, median survival 9.5 months. Conclusion: These data suggest that CapDoc is a well tolerated convenient out-patient combination with very promising efficacy. [Table: see text]
Correlation of epidermal growth factor receptor (EGFR) mutation, immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) in esophageal squamous cell carcinoma (ESCC)
Authors: Sunpaweravong P. , Suwiwat S. , Sunpaweravong S. , Puttawibul P. , Varella-Garcia M. , Mitarnun W. 
Published: March 2020

4085 Background: ESCC remains a devastating cancer in Southern Thailand and novel therapeutic approach needs to be explored. EGFR tyrosine kinase (TK) inhibitor is a potential therapeutic agent against EGFR-expression tumors including ESCC. Forty-nine percent of ESCC patients in our institution overexpressed EGFR protein and 15% had EGFR gene amplification as published previously. Mutations within EGFR TK domain, particularly in exon 19 and 21, EGFR amplification or polysomy, and EGFR overexpression on IHC have all been associated with sensitivity and benefit to EGFR inhibitor treatment. To our best knowledge, no data on EGFR mutations in ESCC have been reported. This prompted us to perform analysis of EGFR mutations and correlate the status of each of these characteristics in ESCC. Methods: We studied 35 patients with ESCC whose data on EGFR IHC and FISH were available. DNA extraction was performed using a QIAamp DNA Kit. PCR for EGFR detection, using the oligonucleotide primers for amplification of exon 19 and 21, was sequenced and analyzed, using ABI Prism 377 sequencing analysis system and the Big Dye Terminator V3.0 Ready Reaction Cycle Sequencing Kit (ABI Prism). Results: Among 35 ESCC specimens evaluated, no EGFR somatic mutations in exon 19 or 21 were detected. Conclusions: EGFR mutations in exon 19 and 21 of ESCC were not identified in this study. EGFR overexpression and amplification do not correlate with EGFR mutation in Thai patients with ESCC. A clinical study of an EGFR inhibitor in esophageal carcinoma has been going on in our institution and the molecular markers as predictive factors need to be further evaluated and correlated with treatment outcome. No significant financial relationships to disclose.
Clinical and molecular evaluation of patients with esophageal adenocarcinoma from the United States and Japan
Authors: Gibson M. , Orita H. , Brock M. , Xu L. , Yang S. , Heitmiller R. , Herman J. , Gabrielson E. , Forastiere A. 
Published: March 2020

4087 Background: Esophageal adenocarcinoma (EAC) is more common than squamous cancer (ESC) in the US versus Japan (J); however, EAC in J is now more frequently recognized. We assessed features of EAC in J and US patients to determine if the cohort of EAC in Japan is similar to the US. Methods: Patients with EAC who underwent primary curative surgery were identified by reviewing all surgical cases from 1998 to the present at Johns Hopkins Hospital (n = 57) and Juntendo University Hospital (n = 20). Clinical variables included: gender, age, pathologic stage, date of surgery and of death. Methylation of APC, E-cadherin, MGMT, ER, p16, DAP-kinase and TIMP3 was determined with methylation specific-PCR for each J patient and compared to historical control US EAC patients. Logistic regression and survival analysis were used to evaluate the relationship between clinical variables and methylation status to outcome in these two patient groups. Results: Age and gender were similar in each cohort. Gender (50M/6F in US; 16M4F p = 0.29). Median age (65.5 in US; 64 in J). Path stage was lower in US patients but not significant compared to J patients. Stage distribution US: stage I (n = 30), IIA (n = 2), stage IIB (n = 6), stage III (n = 9) and stage IV (n = 4). Stage distribution in J: stage I (n = 6), IIA (n = 5), stage IIB (n = 5), stage III (n = 3) and stage IV (n = 3). Path stage unavailable in 5 US patients. Overall median survival was 4.2 years. Median survival for US was 2.9 years but not reached for J (note 15/20 J patients outcome not known). For the combined cohort, age and path stage (adjusted for clinical co-variates) correlated with worse survival. Age HR 1.05; 95% CI 1.01–1.09. Pathologic Stage HR 1.4; 95% CI 1.19–1.65. These were also predictive within each subgroup. The fraction of patients with methylation is available for three genes: APC (66% US; 70% J). p16 (39% US; 20% J). MGMT (63% US; 75% J). Conclusions: Clinical data are similar for US and J patients with EAC. Early stage in US patients may by due to induction chemoRT in the US. Predictors of survival (age and pathologic stage) are also similar. This suggests that EAC is similar in US and J patients, perhaps reflecting similar environmental and molecular causes. Methylation data for all 7 genes and their correlation with outcome will be presented at the meeting. No significant financial relationships to disclose.
KRAS mutation analysis in patients (pts) with locally advanced pancreatic cancer (LAPC) treated with gefitinib and chemoradiation therapy (CT-RT) in a phase I trial
Authors: Chen H. , Raben D. , Schefter T. , Kane M. , McCarter M. , Olsen C. , McCoy K. , Eckhardt S. G. , Gumerlock P. H. 
Published: March 2020

4106 Background: Correlative studies that incorporate biomarkers to rapidly analyze response to new agents are needed. Unique to pancreatic cancer is the high incidence of KRAS mutations (over 90%). This pilot study evaluated plasma KRAS mutations for disease monitoring in LAPC pts treated on a Phase I trial combining CT-RT with the EGFR inhibitor, gefitinib. Methods: DNA was extracted from plasma of 11 pts collected at 3 timepoints: pre-gefitinib, pre-CT-RT, and post-gefitinib+CT-RT. Matched tissue DNA was obtained from 4 pts with available paraffin blocks. KRAS codon 12 mutations were detected using a two-stage RFLP-PCR assay. Cell line controls: Calu-1 (mutant KRAS) and LNCaP (wild-type KRAS). Mutations were confirmed by direct DNA sequencing. Results were related to pt clinical data. Results: KRAS mutations were detected in the pre-gefitinib plasma of 5/11 pts, and in the matched tumor tissue of 3/4 pts. Of the 5 pts with plasma KRAS mutations, 2 pts with no detectable mutant KRAS in the plasma post-gefitinib+CT-RT had overall survival of 8 and 21 months, whereas 2 pts who retained mutant KRAS had overall survival of only 2 and 5 months, and one pt withdrew early. Of the 3 tumor tissues containing mutant KRAS, the mutations were also detectable in the matched plasma in 2 pts (67%). KRAS codon 12 mutations spectrum: 4 GGT→GAT, 2 GGT→GTT and 1 GGT→AGT. Conclusions: Plasma KRAS mutations are readily detectable in LAPC pts, and the clearance or persistence of plasma KRAS mutations after treatments reflected the clinical course in some cases. The use of plasma KRAS mutation as a marker of survival and response will be further assessed in a recently approved phase I trial using a proteasome inhibitor with chemoradiation at the University of Colorado. No significant financial relationships to disclose.
Phase II study of gemcitabine, capecitabine and bevacizumab for advanced pancreatic cancer (APC) with ECOG PS 0–1
Authors: Javle M. M. , Iyer R. V. , Yu J. , Wilkinson D. Q. , Nava H. R. , Phelan J. T. , Litwin A. M. , Haney J. M. , Gibbs J. F. , Kuvshinoff B. W. 
Published: March 2020

4117 Background: Gemcitabine and capecitabine chemotherapy may result in improved survival for patients (pts) with APC and good performance status. Preclinical synergy between these agents and bevacizumab (BV) and encouraging results of angiogenic inhibition in PC formed the rationale for this study. Endpoints: Primary: progression-free survival (PFS), Secondary: response rates, overall survival, toxicity assessment and quality of life (QOL). Methods: Pts with APC (inoperable stage III or IV), ECOG PS 0–1, normal organ and marrow function were eligible. Schema: Avastin 15 mg/kg, q 21 days; capecitabine 650 mg/m2 bid x 14 days, both starting day 1; gemcitabine 1000 mg/m2 days 1 & 8; cycles repeated q 21 days. The study has a power of 0.8 at 0.05 significance level to determine if PFS is ≥ 4.1 months with study regimen (2.5 months with gemcitabine). Results: Twenty-six (of planned 34) pts have been enrolled; 22 pts were evaluable for response (4 too early). Median age 64 years (range 38–79), 12 are male, one stage III, 25 stage IV. Median of 3 cycles/pt (range 1–16) with a total 105 cycles. Responses (RECIST): 7 partial responses (32%; 95% CI: 14%-55%), 12 stable disease, 3 progressive disease. The median PFS is 8.2 months (C.I. 4.7–11.3). Estimated median overall survival is 9.1 months (C.I. 8.3-undetermined). Five% improvement in QOL occurred in 7/15 pts (95% C.I: 21–73%). Grade 3 toxicities: proteinuria (n=1), neutropenia (n=2), thrombocytopenia (n=1), pulmonary embolism (n=2), nausea (n=2), emesis (n=2), diarrhea (n=1), infection (n=1), anemia (n=1) and hemorrhage (n=1). Grade 4 toxicities: neutropenia, cerebrovascular accident and diarrhea (n=1, each). One treatment related death occurred (hemorrhage). Conclusion: In this interim analysis, encouraging response rates, PFS and QOL improvement occurred with the addition of BV to gemcitabine and capecitabine. Toxicity profile is acceptable. Accrual is ongoing. Acknowledgement: Study is supported by a grant from NCCN and by Genentech. [Table: see text]