bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter randomized phase II trial of cisplatin, irinotecan plus bevacizumab (PCA) versus docetaxel, cisplatin, irinotecan plus bevacizumab (TPCA) in patients (pts) with metastatic esophagogastric cancer (MEGCA).
Authors: Enzinger Peter C. , Kwak Eunice Lee , Szymonifka Jackie , Abrams Thomas Adam , Regan Eileen , Malinowski Paige , Shih Kent C. , Allen Jill N. , Jackson Nadine , Chan Jennifer A. , Fidias Panos , Ryan David P. , Fuchs Charles S. , Bendell Johanna C. 
Published: March 2020

4027 Background: In MEGCA, PCA has a 65% response rate (RR) and 8.3 mos time to progression (Shah. JCO 2006); TPCA has a 66% RR and 8.9 mos progression-free survival (PFS) (Enzinger. ESMO 2008 updated). Methods: Chemo naive pts with MEGCA were stratified: ECOG (0/1 vs. 2) and disease site (Gastric or GEJ/esophageal) and randomized 1:1 to PCA or TPCA. PCA -- cisplatin 30mg/m2 and irinotecan 65mg/m2 on d1, 8, and bevacizumab 10 mg/kg d1 docetaxel 30mg/m2, cisplatin 25mg/m2 and irinotecan 50mg/m2 on d1, 8, and bevacizumab 10 mg/kg d1. Cycles were 3 weeks. Response assessment - q6wks (RECIST 1.1). Primary endpoint was PFS. Results: 85 patients: median age=61 (40-85); male/female= 70/15; ECOG: 0/1/2=(34/49/2); gastric/GE junction/esophageal=27/21/37; measurable/evaluable: 78/7; sites of metastatic disease (# of pts): lymph nodes (34), liver (31), lung (11), bone (5), abdomen (4), peritoneum (4), other (11). There were two treatment-related deaths: esophageal hemorrhage, sudden death (both TPCA). Conclusions: Both regimens were efficacious and reasonably well tolerated. The addition of docetaxel to the attenuated PCA combination did not significantly improve efficacy. [Table: see text]
The pattern and timing of disease recurrence in squamous cancer of the anus: Mature results from the NCRI ACT II trial.
Authors: Sebag-Montefiore David , James Roger , Meadows Helen , Begum Rubina , Cunningham David , Northover John , Ledermann Jonathan A. , Beare Sandra , Kadalayil Latha , Glynne-Jones Robert ,   ACT II Study Group
Published: March 2020

4029 Background: Concurrent chemoradiation (CRT) is standard treatment for patients with squamous cell carcinoma of the anus. Although the majority of patients achieve long term disease control, locoregional failure is either detected early (failure to enter complete remission) or at a later date as locoregional recurrence. We explore the pattern and timing of disease recurrence within a phase III trial (ACT II), which mandated standardised radiation fields and doses (50.4Gy in 28 daily fractions). Methods: The UK ACT II trial recruited a total of 940 patients (2000 -2008) and compared cisplatin with mitomycin when combined with 5flurouracil CRT and two cycles of maintenance chemotherapy versus no maintenance using a factorial 2x2 design. Patient characterstics: T1/2 52%, T3/4 46%; N+ 32% N0 62%. The loco-regional response to treatment was assessed by clinical examination at 11, 18 and 26 weeks after CRT. Clinical examination was performed every two months for year 1; 3-monthly for year 2; then 6-monthly for years 3-5. CT scans of chest/abdomen/pelvis were performed at 6,12 24 months. Sites of failure were recorded on a case record form (primary site [PS], inguinal [ING], pelvic nodes [PEL], metastatic [METS]. Results: After a median follow up of 5 years, the crude pelvic failure (PF) rate is 18% (163/924). Of the 163 PF, 133 pts (82%) were pelvic only and 30 (18%) had PF + metastasis. 93% of all pelvic recurrences were detected during the first three years (54% yr 1, 26% yr 2 and 13% yr 3). The pattern was similar for PF only and PF + mets (data not shown). Only 46 (4%) of patients had [METS] as the first disease related event. 117/133 (88%) patients with PF only are evaluable for analysis of the pattern of failure., 53% occurred at the primary site (PS) only, 23% were PS + nodal (5% [ING] 13% [PEL] and 5% [ING+PEL], and 25% nodal only (6% [ING],14% [PEL] and 5% [ING+PEL]). Conclusions: The ACT II trial results with mature follow-up demonstrate a low rate of pelvic failure. Intensive follow up to detect potentially salvageable pelvic failure should be restricted to a maximum of three years in future trials as only 7% of relapses occur beyond this time point.
Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil (5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIV-positive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): Safety and preliminary efficacy results.
Authors: Garg Madhur , Lee Jeanette Y , Kachnic Lisa A. , Catalano Paul J. , Henry David H. , Cooley Timothy Patrick , Ratner Lee , Wachsman William , Aboulafia David Michael , Benson Al Bowen , Palefsky Joel , Whittington Richard , Mitsuyasu Ronald T. , Sparano Joseph A. ,   Eastern Cooperative Oncology Group (ECOG); AIDS Malignancy Consortium (AMC)
Published: March 2020

4030 Background: Epidermal growth factor receptor (EGFR) expression and HPV infection are common in SCAC. We therefore initiated 2 phase II studies to evaluate the safety and efficacy of the EGFR inhibitor CX given concurrently with CDDP/5-FU/RT in HIV-positive (AMC045) and immunocompetent (E3205) patients with SCAC. Methods: All patients received CX (400 mg/m2 loading, then 250 mg/m2/wk IV x 6-8 wks) plus CDDP (75 mg/m2 IV q28 days x 2) and 5-FU (1000 mg/m2/day IV infusion days 1-4 q 28 days x 2) concurrently with RT (45-54 Gy) beginning with CX dose 2. Patients in E3205 also received 2 cycles of CDDP/5-FU alone prior to CX/CDDP/5-FU/RT; this was discontinued on recommendation of the NCI Anorectal Task Force after 28 patients. Both trials were powered to detect a reduction in 3-year local-regional failure (LRF) rate from 35% to 17.5% (alpha=0.10, beta=0.10), the primary end point. Other endpoints included progression free survival (PFS) and overall survival (OS). The results below include complete toxicity and preliminary efficacy data (including only the first 28 patients from E3205). Results: Expedited reporting was required for type I (any grade 5, grade 4 cardiac) or II (grade 4 RT skin, diarrhea) adverse events, with prespecified rates of >5% or >20%, respectively defined as unacceptable. Early stopping rules were not invoked for either trial. LRF rates data will be presented after more detailed case review is completed. Conclusions: CX plus CDDP/5-FU/RT is feasible in patients with SCAC, including patients with HIV infection. Preliminary safety and efficacy data appear encouraging, but accrual without neoadjuvant CDDP/5-FU continues in E3205, and additional followup of both study cohorts is required in order to determine whether pre-specified efficacy endpoints were met. [Table: see text]
Randomized phase II trial of gemcitabine plus S−1 combination therapy versus S−1 in advanced biliary tract cancer: Results of the Japan Clinical Oncology Group study (JCOG0805).
Authors: Ueno Makoto , Okusaka Takuji , Mizusawa Junki , Takashima Atsuo , Morizane Chigusa , Ikeda Masafumi , Hamamoto Yasuo , Ishii Hiroshi , Hara Hiroki , Fukutomi Akira , Furukawa Masayuki , Nagase Michitaka , Yamaguchi Taketo , Yamao Kenji , Nakamori Shoji , Ioka Tatsuya , Iguchi Haruo , Miyakawa Hiroyuki , Boku Narikazu , Furuse Junji ,   Japan Clinical Oncology Group (JCOG)
Published: March 2020

4031 Background: Gemcitabine plus cisplatin combination (GC) therapy is the standard therapy for advanced biliary tract cancer (BTC). In previous trials, gemcitabine plus S-1 combination (GS) therapy and S-1 mono-therapy had shown considerable efficacy in patients with BTC. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen for a subsequent phase III trial. Methods: Chemotherapy-naive patients with recurrent or unresectable BTC (gallbladder [GB], intrahepatic biliary duct [IHBD], extrahepatic biliary duct [EHBD], ampulla of Vater [AV]), an ECOG PS of 0 - 1, and adequate organ function were randomly assigned to receive GS (gemcitabine: 1,000 mg/m2, iv, days 1 and 8; S-1: 60 mg/m2, p.o., days 1 - 14, every 3 weeks) or S-1 (80 mg/m2, p.o., days 1 - 28, every 6 weeks). We assumed that %1-year survival of one regimen is 30% and that of the other regimen is more than 40%. To ensure at least 85% probability of correct selection, 98 eligible pts are required. The decision rule was that the regimen with higher %1-year survival will be considered as more promising regimen. Results: From February 2009 to April 2010, 101 pts (GB, n=38; IHBD, n=35; EHBD, n=20; AV, n=8) were randomized (GS, n=51; S-1, n=50). For the GS arm and S-1 arm, %1-year survivals were 52.9% and 40.0%, the median survival time were 12.5 and 9.0 months (hazard ratio 0.86 [95%CI 0.54-1.36]; p=0.52), and the median progression-free survival time were 7.1 and 4.2 months (0.44 [0.29-0.67]; p<0.0001). Grade 3/4 hematological toxicities were more frequent in the GS arm than in the S-1 arm, (percentage in GS/S-1 arms): neutropenia, 60.8/4.0; leukocytopenia, 29.4/2.0; hemoglobin, 11.8/4.0; and thrombocytopenia, 11.8/4.0; respectively. Although two treatment-related deaths occurred in the GS arm (pneumonitis, acute myocardial infarction), other grade 3/4 non-hematological toxicities were infrequent and reversible in both arms. Conclusions: The GS arm was superior in %1-year survival to S-1. Here we consider GS to be more promising as the test arm for a subsequent phase III trial comparing with GC.
Final results of a phase I/II study in patients with pancreatic cancer, malignant melanoma, and colorectal carcinoma with trabedersen.
Authors: Oettle Helmut , Seufferlein Thomas , Luger Thomas , Schmid Roland M. , von Wichert Goetz , Endlicher Esther , Garbe Claus , Kaehler Katharina K. , Enk Alexander , Schneider Anneliese , Rothhammer-Hampl Tanja , Grosser Susanne , Kiessling Peter 
Published: March 2020

4034 Background: TGF-β2 overexpression in solid tumors triggers key cancer pathomechanisms, i.e. suppression of antitumor immune responses system and metastasis. Trabedersen specifically inhibits TGF-β2 expression. In the clinical Phase I/II study we evaluate MTD, safety, pharmakokinetics (PK), and efficacy of i.v. trabedersen in patients with advanced tumors. Methods: A total of 61 patients with pancreatic cancer (PancCa, n=37), malignant melanoma (MM, n=19), or colorectal carcinoma (n=5) were treated with i.v. trabedersen as 2nd to 4th-line therapy with escalating doses in 2 treatment schedules. (1st schedule: 7d on, 7d off; 2nd schedule: 4d on, 10d off; up to 10 cycles). Within the 1st schedule, the MTD was established at 160 mg/m2/d. In the 2nd schedule dose-escalation was stopped before reaching MTD. In the Phase II-part of the study further PancCa and MM patients were treated with 140 mg/m2/d. For assessment of PK parameters, plasma time profiles were analyzed for trabedersen and its n-1 to n-5 metabolites by non-compartimental analysis. Results: Trabedersen was safe and well-tolerated. The only expected adverse reaction identified is non-serious and transient thrombocytopenia. Only 2 SAEs (gastrointestinal hemorrhage und pyrexia) were considered as possibly related to study medication. Further clinical development will focus on PancCa patients receiving 140 mg/m2/d trabedersen as 2nd-line treatment. Survival analysis of these patients revealed a mOS of 13.4 months (n=9; 95% CI: 2.2, 39.7). One PanCa patient had a complete response of liver metastases and is still alive after 75 months. Promising efficacy data were also seen in MM patients enrolled into the last cohort (140 mg/m2/day) with a current mOS of 9.3 months (n=14; 95% CI: 6.5, 12.2). PK analyses showed for both treatment schedules that exposure to trabedersen was in the expected range for all doses and half-life of trabedersen (1.12 to 2.08 hrs) as well as clearance (2.22-4.37 L/h*m2) were independent of dose. Conclusions: Trabedersen showed excellent safety and encouraging survival results in the Phase I/II clinical study. A randomized, active-controlled study in 2nd line stage IV PanCa patients is in preparation.
Incidence and characterization of venous thromboembolic events (VTE) in patients with pancreatic cancer: Effect of timing of VTE on survival.
Authors: Shethia Maithili A , Hegde Aparna , Zhou Xiao , Overman Michael J. , Vadhan-Raj Saroj 
Published: March 2020

4037 Background: Patients (pts) with pancreatic cancer are at high risk for VTE, and the occurrence of VTE can affect pts’ prognosis. The purpose of this study was to evaluate the incidence of VTE and the impact of timing of VTE (early vs. late) on survival. Methods: Medical record of 260 pts with pancreatic cancer, newly referred to UT MDACC during one year period from 1/1/2006 to 12/31/2006, were reviewed for the incidence of VTE during a 2-year follow-up period from the date of diagnosis. All VTE episodes were confirmed by radiologic studies. Survival analysis was conducted using Kaplan-Meier analysis and Cox proportional hazard models. Results: Of the 260 pts, 47 pts (18%) had 51 episodes of VTE during the 2-year follow-up. The median age of the pts with VTE was 61 years (range: 28-86) and 53% were males. Of the 47 pts with VTE, 27 (57%) had PE, 19 (40%) had DVT and 1 had concurrent PE/DVT. Three pts had recurrent VTE during the study period. Median follow-up time for OS was 192 days (range: 1-1652 days). Kaplan-Meier Survival analysis showed that those who developed VTE earlier (within 30 or 90 days) had shorter median overall survival (OS) compared with those who had VTE beyond these time points. The hazard ratios, 95% CI, and median OS at 1 year are summarized in the table below. Conclusions: The incidence of VTE is high in pts with pancreatic cancer. The timing of VTE had a significant impact on OS; pts who had an early development of VTE had a shorter overall survival. [Table: see text]
A phase III trial of ganitumab (GAN, AMG 479) with gemcitabine (G) as first-line treatment (tx) in patients (pts) with metastatic pancreatic cancer (MPC): An analysis of safety from the GAMMA trial (GEM and AMG 479 in Metastatic Adenocarcinoma of the Pancreas).
Authors: Fuchs Charles S. , Ikeda Masafumi , Bodoky Gyorgy , Okusaka Takuji , Ohkawa Shinichi , Mizuno Nobumasa , Swieboda-Sadlej Anna , Sobrero Alberto F. , Haddad Vincent , McGreivy Jesse S. 
Published: March 2020

4042 Background: GAN is an investigational, fully human, monoclonal antibody inhibitor of IGF1R. GAMMA is assessing the safety and efficacy of GAN plus G as first-line tx in MPC pts (ClinicalTrials.gov ID: NCT01231347). Methods: This is an ongoing, global, phase III, double-blind study. Pts are randomized 2:2:1 to receive placebo, GAN 12 mg/kg, or GAN 20 mg/kg (IV; days 1 and 15 Q28D) with G 1000 mg/m2 (IV; days 1, 8, and 15 Q28D). The planned sample size is 825. Primary endpoint: overall survival. Key secondary endpoints: progression-free survival, 1-year survival rate, patient-reported outcomes, and safety. This study includes multiple planned safety analyses conducted by an independent Data Monitoring Committee (DMC). The current predefined safety analyses occurred when 150pts received ≥ 1 cycle of tx. Results: As of Sep 16, 2011, 207 pts are included in this aggregate analysis: 50% male; median age, 63 yrs (range 36-83); ECOG PS 0/1, 50%/50%. Of the 207 pts, 204 pts received study tx, and 61 pts ended study tx. Most frequent adverse events (AE) are shown (table). Ten pts (5%) died during or within 30 days of the end of tx. Seven events were attributed to or associated with disease progression. One event of cardiac failure was reported to be possibly tx related. Pulmonary embolism was suspected but not confirmed. Conclusions: The GAMMA study continues per protocol. The only grade 3/4 AE occurring in more than 5% of patients to date is neutropenia. [Table: see text]
Updated survival analysis of preoperative gemcitabine (gem) plus bevacizumab (bev)-based chemoradiation for resectable pancreatic adenocarcinoma.
Authors: Shroff Rachna T. , Varadhachary Gauri R. , Crane Christopher H. , Lee Jeffrey Edwin , Lee Jeffrey H. , Ho Linus , Tamm Eric P. , Evans Douglas B. , Abbruzzese James L. , Wolff Robert A. 
Published: March 2020

4051 Background: Preop therapy for resectable pancreatic cancer (PC) maximizes access to multimodality therapy and increases the R0 resection rate. Based on our phase I chemoradiation (chemoRT) trial in PC patients, we hypothesized that the addition of bev to gem-based chemoRT in pts with resectable PC may allow more pts to undergo pancreaticoduodenectomy (PD), improve the rate of R0 resections, and prolong overall survival. Methods: Pts with biopsy proven, stage I/II adenocarcinoma of the pancreatic head or uncinate process received 6 weekly infusions of gem (400 mg/m2) and 3 infusions of bev (10 mg/kg, every 2 wks) with concomitant RT, 50.4 Gy at 1.8 Gy/fr. Pts were restaged 4-6 wks after the last dose of radiation. Those without disease progression and with good PS underwent surgery. Pts with adequate recovery received bev (10 mg/kg) every 2 weeks for 3 mo starting ~ 6 wks after surgery. Results: This study enrolled 11 of a planned 31 pts but was terminated early due to unforeseen postop complications. Median age is 64 yrs; all pts had ECOG-PS 0-1. Median CA19-9 was 52. Median follow-up from surgery was 41 mths. All completed chemoRT; 10 underwent restaging and 1 pt died from cardiac arrest before restaging. 9 pts (90 %) went to surgery and underwent a successful R0 PD. Pathologic PR rate (>50 % tumor kill) was 56 %. As we have previously reported, preop grade 3-4 toxicities were infrequent and major postop complications occurred in 5 of the 9 pts (56%) who underwent PD. Median overall survival (OS) was 30.1 mths (range: 2.6 - 63.9) for the entire cohort. Of the 9 resected pts, median OS was 45.5 mths with 5 of 11 pts (45%) achieving survival longer than best historical control (median 58.2 mths). Conclusions: The addition of bev to our prior backbone of gem-based preoperative chemoRT led to a higher resection rate (90%) than our previous protocols. Updated survival results of this study are promising. Taken together, these results may prompt further investigation of this regimen with modifications in the timing of bev delivery.
International experts’ panel for the development of guidelines for the definition of time to event endpoints in clinical trials (DATECAN project): Results for pancreatic cancer.
Authors: Bonnetain Franck , Doussau Adelaide , Mathoulin-Pelissier Simone , Bonsing Bert A , Glimelius Bengt , Haustermans Karin , Conroy Thierry , Van Laethem Jean-Luc , Labianca Roberto , Macarulla Teresa , Mauer Murielle E. , Lutz Manfred P. , Tabernero Josep , De Gramont Aimery , Hammel Pascal , Aust Daniela Ellen , Ducreux Michel , Taïeb Julien , Neoptolemos John P. , Collette Laurence ,   DATECAN
Published: March 2020

4053 Background: Variability in the definition of survival endpoints in oncology trials was identified (Mathoulin et al.JCO 2008). Lack of a formal consensus could cause this, which limits inter-trial comparisons. The DATECAN project aimed at obtaining a formal consensus recommendation for defining survival endpoints for randomized clinical trials (RCTs) in the following cancer sites: pancreas, sarcoma/GISTs, breast, colorectal, gastric/œsophagus, head and neck, kidney-bladder. We report results for pancreatic cancer. Methods: Based on a literature review of RCTs (2006-2009), we identified survival endpoints and events currently used. A 2-round modified Delphi method using RAND scoring (range:1-9) was used to reach consensus. Academic research groups were contacted for participation in order to select clinicians and methodologists for Pilot and Scoring groups (>30 experts/localization). Results: The Pilot group identified 14 endpoints that needed definition through consensus, such as progression free survival (PFS), time-to-treatment failure, time to quality of life deterioration. Endpoint definitions were seeked by disease setting (detectable disease vs not). Amongst the 52 European experts contacted, 33 and 30 participated to the 1st and 2nd round respectively. The experts scored a total of 204 events; a consensus was reached for 25 (12%) at the 1st round and 156 (76%) at the 2nd round. As example PFS was defined as time interval between the date of randomization, and the day of first local, regional progression or occurrence of distant metastases (including liver or non liver metastases) or occurrence of 2nd pancreatic cancer or death (all causes), whichever occurs first. The consensus was finalized during a face-to-face meeting organized during the ESMO 2011 congress and general rules were proposed for final ratification. Conclusions: Based on this consensus, an European charter is being finalized and proposed for endorsement to all academic groups in order to harmonize results and to allow formal comparisons of pancreatic RCTs. The impact of these definitions on trial results will be also investigated in a further project.
A phase II study of neoadjuvant therapy with cisplatin, docetaxel, panitumumab plus radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051).
Authors: Reed Carolyn E , Decker Paul A. , Schefter Tracey E. , Meyers Bryan F , Ferguson Mark K. , Oeltjen Amy R , Putnam Joe B. , Cassivi Stephen David , Lockhart A. Craig ,   American College of Surgeons Oncology Group
Published: March 2020

4062 Background: Multiple clinical trials have incorporated preoperative chemotherapy and radiation (RT) in an attempt to improve local tumor control, distant disease failure and overall survival rates for locally advanced but resectable adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ). This multicenter, cooperative group study combined active chemotherapy agents cisplatin (C), docetaxel (D) and the targeted EGFR agent panitumumab (P) in the induction phase followed by concurrent chemotherapy (CDP) and radiation. Pathologic complete response (pCR), a surrogate for improved survival, was the primary endpoint. Methods: From 01/15/09 to 07/22/11, 70 patients (pts) with Siewert I or II adenocarcinomas and clinical stages T3N0M0, T2-3N1M0 or T2-3N0-1M1a (celiac LN ≤ 2 cm) were accrued. Patients received cisplatin (40 mg/m2), docetaxel (40 mg/m2) and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, 9 with RT (5040 cGy, 180 cGy/day x 28d) beginning week 5. The decision rule had a 90% power with a 0.10 significance level to detect a pCR rate of at least 35%. Secondary objectives included near-pathologic complete response (near-pCR), toxicity, and overall and disease-free survival rates. Results: Five pts were ineligible. Of the remaining 65 pts (59 M, 6 F; median age 61), 12 pts did not undergo surgery (5 progressed, 4 refused, 3 other). Of the 58 evaluable pts, the pCR rate was 32.8% (90% CI: 22.6% -42.9%) and near-pCR 22.4% (90% CI: 13.4%-31.4%). Total doses of C, D, and P were achieved in 76%, 80%, and 73%, respectively (n = 70). 66 pts (94%) received the total RT dose. Sixteen pts (23%) had a grade 4+ non-heme adverse event possibly related to treatment. Venous thrombosis (5 pts) was most common. Conclusions: The CDP regimen in the neoadjuvant setting in patients with esophageal adenocarcinomas is active (pCR + near-pCR = 55.2%) and feasible. The toxicity though tolerable is substantial.