bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant and adjuvant chemotherapy without radiation for esophageal cancer
Authors: Ardalan B. , Spector S. , Livingstone A. S. , Franceschi D. , Ganjei-Azar P. , Lima M. , Sparling L. , Walker G. , Bowen-Wells C. P. 
Published: March 2020

4054 Background: A Phase II trial to evaluate neoadjuvant (NAD) and adjuvant (AD) combination chemotherapy (CT) without radiation therapy (RT), for Stage III esophageal adenocarcinoma. Methods: Stage III disease by CAT scan or EUS and ECOG performance status 0–1. The CT cycles included Cisplatin, Taxol, FUDR and Leucovorin. The chemotherapy was given for 16 weeks prior to surgery, followed by adjuvant chemotherapy for patients whose pathology at the time of surgery demonstrated microscopic disease. Survival was estimated via Kaplan Meier. Results: 33 patients were enrolled: 28 completed NAD, 15 received AD. Of 33 pts given NAD, 16 had grade I/II toxicity and 14 had grade III/IV. In addition, 6 of 15 pts receiving AD had grade I/II toxicity and 3 had grade III/IV during that phase of treatment. Thirty-two (32) patients went to surgery, 30 patients were resected: 24 transhiatial and 6 transthoracic. Of the 28 patients who completed NAD, 19 (68%) demonstrated improvement in dysphagia; 11 (41%) gained weight, and 7 (26%) had no weight change. Pathologic response to NAD: 30 patients had partial response and 2 patients had progressive disease, one died prior to surgery, post carotid endarterectomy. Ten (10) patients showed no gross disease. Twenty-three (23) patients have expired, 17 disease related with distant metastasis, 1 with local recurrence and distant metastasis, 3 non-disease related and 2 unresectable cases. Kaplan-Meier estimates of overall survival at 1, 3, and 5 years were 73% (95% CI: 58 to 88%), 52% (95%CI: 34 to 69%), and 29% (95% CI: 13 to 45%), respectively. Median survival was 42 months (95% CI: 14 to 52 months). Ten (10) patients are alive after a median follow up of 73 months (range 45 to 89). Seven (70%) of the surviving patients received both NAD (2 cycles) and AD (1 to 2 cycles) and all had no evidence of disease as of last clinical and radiological evaluation. Conclusions: This regimen of combination CT for locally advanced esophageal adenocarcinoma is safe and comparable with those regimens that contain RT. There has been 1 local recurrence; 17 patients have recurred distantly. Omission of RT may allow for a more aggressive CT and reduction in the local complications post-surgery. This study needs to be confirmed in a larger phase II or in randomized phase III trial. No significant financial relationships to disclose.
Phase II trial of preoperative (POP) irinotecan (I) + cisplatin (C) and radiotherapy for esophageal cancer
Authors: Visbal A. L. , Darling G. , Wong R. , Guindi M. , Hornby J. , Feld R. , Ringash J. , Keshavjee S. , Chen E. , Brierly J. , Knox J. 
Published: March 2020

4056 Background: Esophagectomy (E) for locally advanced esophageal cancer (LAEC) yields limited survival; this phase II trial assess feasibility and efficacy of induction chemo-radiotherapy followed by E. Methods: Patients (pts) with LAEC of the thoracic esophagus (TE) or gastroesophageal junction (GEJ), ECOG PS ≤ 2 and surgical candidates underwent POP I (65mg/m2) + C (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (40Gy/20 fractions (F) during wk 4–7) and external beam boost (10Gy/5F on wk 8); E was performed on wk 12–16 after restaging. Pts receiving 75% of POP chemotherapy were eligible for pathologic (p) evaluation; planned sample size 36 nonM1A pts. Results: 52 pts enrolled from 11/02 to 12/05, mean age 60 yr (33–79), male:40, GEJ:TE/15:37; 37 adenocarcinoma, 13 SCC, 2 other; 13 pts were stage IIA, 7 IIB, 22 III, and 10 IVA. Toxicity during POP treatment included ANC (G3/4:36%), febrile neutropenia (9%), diarrhea (G3:9%), nausea (G3:6%), esophagitis (G3:2%) and anorexia (G3/4:15%); 3 pts stopped treatment due to toxicity, 2 withdrew, 2 progressed becoming non-operable, 1 died of a stroke and 1 from central line sepsis. Clinical response by RECIST was CR:2%, PR:30%, SD:62% and PD in 6%. Dysphagia improved or resolved in 34/47 pts (72%) during POP treatment. Of 43 evaluable pts, 41 underwent E, achieving R0 resection in 98% (1 refused E, 1 pending). Perioperative complications included anastomotic leak (23%), Afib (21%), pneumonia (21%), delirium (10%) and aspiration (10%); 1 pt died from aspiration. 7 pts (17%) achieved pCR, 2 of whom were pretreatment clinical stage IIA, 1 IIb and 4 III; downstaging occurred in 3/7 pts; 15 pts (36.6%) achieved minimal residual disease, 15 (36.6%) pPR, and 4 (9.8%) pSD. At a median (med) follow-up of 15.2 months (1.3–34.5m), 16/52 patients died (med & 2yr overall survival (OS) of 29 m & 66%). Of 41 resected pts, 17 recurred (med & 2yr disease free survival (DFS) of 20m & 46%) of whom 10 died of progression (med & 2-yr OS of 29m & 68.4%). 2yr DFS & OS was 83% & 86% in pCR vs 41% & 76% in non-pCR. Conclusion: In LAEC, induction I/C and radiotherapy followed by E is associated with 72% dysphagia improvement, a significant but manageable toxicity profile, and encouraging survival compared to historical controls. [Table: see text]
Preoperative oxaliplatin (O), docetaxel (D), capecitabine (C), and concurrent radiation therapy (RT) for patients (pts) with localized esophageal cancer: A phase I/II trial of the Minnie Pearl Cancer Research Network
Authors: Barnes E. K. , Spigel D. R. , Greco F. A. , Meluch A. A. , Yardley D. A. , Burris H. A. , Shipley D. L. , Patton J. F. , Farley C. , Hainsworth J. D. 
Published: March 2020

4058 Background: Preoperative chemoradiotherapy improves outcomes for pts with resectable esophageal cancer compared with surgery alone. We previously reported a 41% 3-year progression-free survival (PFS) with preoperative paclitaxel/carboplatin/5FU/RT in a large phase II trial. The present multicenter community trial examined the role of a newer combination regimen. Methods: The primary endpoints were to assess the safety and response rate (RR) of O/D/C/RT in pts with resectable stage I-III cancer of the mid-/distal-esophagus or GE junction. Treatment (tx): O 40 mg/m2 IV and D 20 mg/m2 IV weekly x 5; C 1000 mg/m2 PO BID D1–7, 15–21, 29–35; and RT 45 Gy, 1.8-Gy M-F weekly x 5, starting D1. Pts were resected 4–8 weeks after tx. The phase I portion (n=10) confirmed the safety of O/D/R, and C was added in the phase II portion. Eligibility: measurable disease; ECOG PS 0–1, informed consent. Analysis was by intent to treat. Results: Nineteen pts were enrolled from 9/04 to 10/05 (trial ongoing). Baseline features: median age 60 years (38–77); male/female, 82%/18%; ECOG PS 0/1: 27%/73%; adenocarcinoma/squamous (77%/23%); I (5%), IIA (5%), IIB (33%), III (38%), primary tumor not assessable (19%). All pts completed O/D/C/RT and 14 (74%) were resected. Grade (G) 3/4 non-hematologic toxicity: anorexia (16%), nausea (16%), and fatigue (11%). Other G3/4 non-hematologic toxicities were ≤5%, with no G3/4 esophagitis. No G3/4 hematologic toxicities or tx-related deaths occurred. Complete/partial responses assessed before surgery were seen in 2 pts/11 pts, respectively, for an overall RR of 68% (95% CI 46%-84%). Four pts (21%) had stable disease and 1 pt had progression (1 pt was unevaluable). Pathological complete responses were seen in 8 of 14 evaluable pts (57%). With a median follow-up of 8 months, actuarial 1-year PFS and overall survival (OS) are 66% and 79%, respectively. Median PFS and OS have not been reached. Conclusions: O/D/C/RT is a relatively well-tolerated and active preoperative therapy for pts with resectable esophageal cancer. Additional pts and follow-up are needed to assess this regimen’s benefits. [Table: see text]
Efficacy of patupilone in advanced local or metastatic gastric cancer: A phase IIa trial
Authors: Hsin K. W. , Boyer M. , Ducreux M. , Liu M. , Soo R. , Yeo W. , Williams K. J. , Johri A. 
Published: March 2020

4069 Background: Although the use of taxanes has produced encouraging response rates in patients with advanced local or metastatic gastric cancer, outcomes remain unsatisfactory. Patupilone (EPO906; epothilone B), a novel microtubule stabilizer, has demonstrated anti-tumor activity against a broad range of tumors in vitro and in animal models. The present trial evaluated the efficacy of patupilone in patients with locally advanced or metastatic gastric cancer. Methods: Patients with confirmed gastric adenocarcinoma (defined by RECIST) received patupilone 2.5 mg/m2/wk by single 5- to 7-minute IV infusion for 3 weeks, followed by 1 week off (4-week cycle). Additional inclusion criteria: WHO performance status ≤2, age ≥18 years, life expectancy ≥3 months, and no major hematologic, renal, or hepatic impairment. The primary objective of this open-label, single-arm, 2-stage, multicenter study was to determine the objective response rate (using RECIST) of treatment with patupilone in this population. Results: All 22 patients enrolled were evaluable. Mean age was 61.1 years, 63.6% were men, and 72.7% were oriental. Of 18 patients (81.8%) who completed the study, 10 (45.5%) had disease progression and 8 (36.4%) died from the disease; of 4 discontinuations, 3 were due to adverse events (AEs) and 1 to abnormal alkaline phosphatase. Overall response: 2 patients had partial responses, 6 disease stabilization, 12 disease progression, and 2 unknown. The duration of response in the 2 partial responders was 176 and 113+ days, with the latter censored at 113 days. The most frequently reported AEs were diarrhea (n = 18), nausea (n = 14), vomiting (n = 13), abdominal pain (n = 10), and fatigue (n = 10). Of these AEs, 9 were grade 3 (4 diarrhea, 3 vomiting, 1 nausea, and 1 fatigue) and 2 were grade 4 (1 nausea and 1 vomiting). Grade 4 AEs also included 1 gastric outlet obstruction and 1 dehydration. Conclusions: Patupilone resulted in an overall tumor response/disease stabilization rate of 36.4%, was well tolerated, and may prove to be a viable alternative to taxane treatment in advanced local/metastatic gastric cancer. [Table: see text]
Oxaliplatin and irinotecan chemotherapy in advanced gastric cancer. Final results of a multicenter phase II trial
Authors: Woell E. , Kühr T. , Eisterer W. , Gattringer K. , Greil R. , Zabernigg A. , Hilbe W. , Thaler J. 
Published: March 2020

4070 Background: There are only limited treatment options for advanced gastric cancer. Development of new treatment options is therefore warranted. The aim of this study was to evaluate the safety, feasibility and efficacy of an outpatient Oxaliplatin/Irinotecan combination in patients suffering from unresectable, locally advanced and/or metastatic gastric cancer. Methods: The combination of Oxaliplatin 85 mg/m2 biweekly with Irinotecan 125 mg/m2 biweekly was chosen since it has been shown in colorectal cancer that a biweekly dose of at least 85 mg/m2 oxaliplatin is superior to a lower dose and toxicity of Irinotecan is much lower if given fractionated into two doses. Furthermore the Irinotecan dose below MTD considers concerns about increased toxicity in gastric cancer patients. Results: 43 patients with histologically proven unresectable and/or metastatic gastric adenocarcinoma and no previous palliative chemotherapy and/or immunotherapy were selected. Median age: 61 years (range 32–81 years), male/female ratio: 24/19, PS 0:11 patients, PS <3:32 patients, locally advanced cancer 5 patients, single metastatic site: 19 patients, multiple metastases: 19 patients, previously adjuvant radiochemotherapy: 4 patients. This outpatient regimen was generally well tolerated. Frequently reported adverse events (more than 20% of patients) were grade 1 or 2 and included neutropenia (44% of patients), thrombocytopenia (30%), anemia (77%), nausea 67%), diarrhea (51%), alopecia (35%). Grade 3 and 4 toxicities included neutropenia in 2/43 pts., anemia in 3/43 pts., nausea in 2/43 pts., and diarrhea in 4/43pts. 5 patients were taken off-study due to toxicity (asthenia, nausea, reversible renal failure, diarrhea). Sensory neuropathy occurred only as grade 2 in 14%, no grade 3/4 neurotoxicity was observed. For response 38 patients are assessable with 3 pts. (8%) showing a CR, PR in 19 pts. (50%), SD in 11 pts. (29%), PD in 5 pts. (13%). Median TTP was 5.3 months and median OS 9.5 months. Conclusions: The outpatient combination of a biweekly Oxaliplatin/Irinotecan chemotherapy is well tolerated and shows a response rate within the range of other combination therapies. The favourable toxicity profile makes it an alternative 1st line regimen. [Table: see text]
Incidence of thromboembolic events (TEEs) before and during chemotherapy of patients with advanced gastric and gastroesophageal junction carcinoma (AG-GEJC) on clinical trials
Authors: Tetzlaff E. D. , Baker J. , Ajani J. A. 
Published: March 2020

4073 Background: TEEs are associated with AG-GEJC and chemotherapy can further increase its incidence. We assessed TEEs before and during protocol chemotherapy for AG-GEJC patients. Methods: Patients with AG-GEJC on four approved protocols between August 1997 and September 2003 were assessed for baseline TEEs, new TEEs during therapy, histology, location of the primary, and overall survival. Three protocols evaluated camptothecin-based chemotherapy (irinotecan, peg-camptothecin, and rubitecan) and one evaluated non-camptothecin-based chemotherapy. Results: We studied 191 patients. Median age was 56 (range 20–80), Male:Female 151:40, chemotherapy naïve 132 (69%). 136 patients received irinotecan-based therapy and 55 patients received non-camptothecin-based therapy. Overall, TEEs occurred in 13.6% of patients. At baseline, TEEs were diagnosed in 5.3% of untreated patients and were diagnosed in 8.5% of patients with one prior chemotherapy regimen. During protocol therapy, TEEs occurred in 6.8% of untreated patients and 10.2% of previously treated patients. The most common TEE during protocol treatment was deep vein thrombosis (46.7%). First-line camptothecin-based chemotherapy was associated with TEEs in 6.5% of the patients. Non-camptothecin-based chemotherapy was associated with TEEs in 7.3% of the patients. Untreated patients receiving irinotecan plus cisplatin had the lowest incidence of TEEs (2.6%) during treatment. TEEs increased to 10.3% in second-line therapy with irinotecan plus cisplatin. Age, gender, location of the primary tumor, and histology did not differ between patients with or without a TEE during treatment. Survival data was available for 67 patients. The median survival of patients with a TEE at anytime was 3.7 months while it was 8.1 months for patients with no history of TEE. Conclusions: This is the first report describing TEEs at baseline and during chemotherapy for patients with AG-GEJC treated on chemotherapy protocols. The data show that chemotherapy is associated with higher risk of TEEs and TEEs influence survival. No significant financial relationships to disclose.
Circulating dendritic cell as a new prognostic factor in pancreatic cancer patients
Authors: Satoi S. , Yanagimoto H. , Takai S. , Toyokawa H. , Takahashi K. , Terakawa N. , Yamamoto T. , Kamiyama Y. 
Published: March 2020

4095 Background: Pancreatic cancer is a cancer with very poor prognosis that might be associated with impaired immune defense. Dendritic cells (DC) are important for immune surveillance and play a central role in protection against infection and malignancy. A defective host antitumor immune response may allow tumor cells to escape from the host immune system. The aim of this study is to determine whether circulating DC could be one of new immunological markers that may predict the prognosis of the pancreatic cancer. Methods: We evaluated pretreatment circulating myeloid-lineage DC (C-DC1) rate in the peripheral blood mononuclear cell and various clinical parameters to determine their prognostic value in 104 pancreatic cancer patients (41 resected and 63 unresected patients) seen at our institution. Results: In unresected patients, univariate analysis demonstrated two risk factors for prognosis of albmin < 3.8g/dl (p = 0.0468), and C-DC1 < 0.27% (p = 0.0006), when all patients were divided by the median value of C-DC1 rate. Consequently, multivariate analysis demonstrated that only C-DC1 was a predominant independent predictor of survival (Hazard ratio; 9.330, 95% Confidential interval; 2.595–33.549, p = 0.0006). In resected patients, C-DC1 in patients with advanced disease (Stages 2b-4, n=28) was significantly lower than that in patients with lower staged cancer (Stage 1–2a, n = 13: 0.43 ± 0.67%, Stage 2b-4: 0.24 ± 0.30%, p < 0.05). The overall survival rates in patients with C-DC1 ≥ 0.27% were significantly longer than those in patients with C-DC1 < 0.27 (C-DC1 ≥ 0.27%, n = 20, 1/3 year survival: 100%/64%. C-DC1 < 0.27, n = 21, 1/3 year survival: 68%/26%. P < 0.05). Conclusions: The C-DC1 less than 0.27% could be one of prognostic factors in patients with pancreatic cancer, and such patients could be targets for the future therapeutic trials. No significant financial relationships to disclose.
A phase I study of oxaliplatin, full-dose gemcitabine and concurrent radiation therapy in patients with pancreatic cancer
Authors: Desai S. P. , Ben-Josef E. , Lawrence T. J. , Francis I. R. , Greenson J. K. , Alfred C. E. , Colletti L. M. , Simeone D. M. , Normolle D. P. , Zalupski M. M. 
Published: March 2020

4107 Background: We previously demonstrated safety and efficacy of full dose gemcitabine (GEM) and radiation therapy (RT) in patients (pts) with pancreatic cancer (PC). Our preclinical studies have shown that GEM with oxaliplatin (OX) preserves radiosensitization with synergistic cytotoxicity. To enhance local and systemic treatment effects, we initiated a study of OX and GEM with concurrent RT. Methods: Pts with untreated PC received up to 4 cycles of GEM day 1, 8, 15 and OX days 1, 15 repeated at 28 day intervals. RT (27 Gy in 1.8 Gy fractions to gross tumor volume with 1 cm margin) was given during cycle 1 and repeated in cycle 4. Surgery occurred after cycle 2 in resectable pts. Dose escalation was guided using time-to-event continuous reassessment method (TITE-CRM). Dose levels 1–4 GEM 1 g/m2 IV over 30 min and OX 40, 55, 70, 85 mg/m2 IV over 90 min; dose level 5, 6 OX dose remained 85 mg/m2 but infusion time for GEM 1 g/m2 was increased to 65, 100 min, respectively. Trial objective is to determine dose level associated with DLT thru cycle 2 in ≤ 20% of pts; planned accrual is 40 pts evaluable for DLT. Results: 40 pts have been enrolled (median age 63, men/women 26/14) with resectable (10), unresectable (27), and metastatic (3) PC. 29 pts have completed 2 cycles and 11 pts 4 cycles. After 2 cycles CA19–9 decreased > 50% in 14 of 24 evaluable pts (58%). Six of 8 explored pts underwent margin negative resection with 1 path CR and 2 with small residual microscopic foci only. Per RECIST, CT response of the primary lesion after 2 cycles included 3 PR, 23 SD and 1 PD. Two additional PR were seen after cycle 4. Thirty pts are presently evaluable for DLT; 7 pts have suffered DLT including grade 4 platelets (4), decline in PS (2), GI bleed (1) and grade 3 weight loss (1). Current estimated probability of DLT is 21% (95% CI 11%,34%) for dose level 3 and 24% (95% CI 13%,37%) for dose level 4. Conclusions: The addition of OX 70–85 mg/m2 days 1, 15 to full dose GEM based RT is tolerable and efficacious. A neoadjuvant phase II study in resectable PC using the MTD defined in this phase I study is planned. Supported by Sanofi-Aventis. [Table: see text]
A phase II trial of oxaliplatin plus capecitabine (xelox) as second line therapy for patients with advanced pancreatic cancer
Authors: Xiong H. Q. , Wolff R. A. , Hess K. R. , Varadhachary G. R. , Blais J. C. , Abbruzzese J. L. 
Published: March 2020

4119 Background: There is no established chemotherapy for patients with pancreatic cancer who have progressed on gemcitabine. This trial was designed to explore the efficacy of xelox as second line therapy in patients with pancreatic cancer. Methods: The primary objective was to determine overall survival at 6 months. It was estimated that 40 patients would be needed to detect 50% 6-month survival with 90% credible interval between 37%-62%. Eligibity criteria included biopsy-confirmed diagnosis of adenocarcinoma of the pancreas, one prior systemic chemotherapy, ECOG performance status (PS) 0–2, and adequate hepatic, renal, and bone marrow functions. Oxaliplatin was administered at 130 mg/m2 and capecitabine at 1000 mg/m2 twice daily for 14 days for patients who were younger than 65 and had ECOG PS score 0–1. For patients older than 65 or PS 2, the oxaliplatin dose was decreased to 110 mg/m2 and capecitabine to 750 mg/m2/twice daily. The treatment was repeated every 3 weeks. Tumor measurements were performed every 9 weeks (3 cycles) in patients who had measurable disease by RECIST criteria, although measurable disease was not required. Results: A total of 41 patients were enrolled into the study, 2 were never treated. Among 39 evaluable patients, 17 were female, median age 62 years (45–75), and 8 had ECOG PS 2. For the 36 patients who have completed therapy, the median number of treatment cycle was 3 (range, 1–6). Grade 3 or 4 toxicities included: abdominal pain (2 patients), dehydration (3), diarrhea (2), fatigue (6), gastrointestinal syndrome (including diarrhea and colitis) (4), hand-foot syndrome (1), hematemesis (1), mastitis (1), myocardial infarction (1), nausea/vomiting (2), neuropathy (1), non-neutropenic fever (1), pneumonia (1). One patient had a partial response and 8 others had stable disease. Median survival duration was 5.8 months (95% confidence interval [CI] 3.2–12.1 months). The six month and 1 year survival rate was 48% (95% CI 33%-70%) and 22% (95% CI 9%-51%), respectively. Conclusions: When used in the second line setting, the xelox has promising activity in pancreatic cancer. [Table: see text]
Phase II study of gefitinib and docetaxel as salvage therapy in patients (pts) with advanced pancreatic adenocarcinoma (APC)
Authors: Shadad F. , Matin K. , Evans T. L. , Volkin R. L. , Kiefer G. J. , Schlesselman J. J. , Cai C. , Schmotzer A. , Dranko S. , Ramanathan R. K. 
Published: March 2020

4120 Background: There is no standard-of-care second-line chemotherapy for APC. The combination of docetaxel and gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) shows enhanced preclinical activity compared to docetaxel alone. Docetaxel alone has activity in APC, and this phase II trial is designed to evaluate the combination. The primary endpoint is survival with an accrual goal of 45 patients to detect an improvement to 5.25 months (mo) in median survival time by one-sided log-rank test at level α = 0.05. Methods: Patients with APC and one prior chemotherapy regimen are eligible for study; EGFR over-expression is not required. Gefitinib is administered at the dose of 250 mg/day orally without interruption. The initial dose of docetaxel was 75 mg/m2 every three weeks (one cycle), but was reduced to 60 mg/m2 due to a high incidence of febrile neutropenia. Results: 31 pts, all with prior gemcitabine therapy, have been enrolled on study to date, with 26 evaluable for toxicity. Patient characteristics: 62% male; 92 % with ECOG performance status 0/1, 8% ECOG of 2; median age 64 years (range 47–82 years). The best response is stable disease (5 pts), median cycles administered 2 (range 1–12). Thus far the median survival time is 4.4 mo, with median time to progression of 2.5 mo. Grade (G) 3/4 febrile neutropenia occurred in 8 out of 18 pts treated at the 75 mg/m2 dose of docetaxel; none has been seen with the 60 mg/m2 dose. Other G 3/4 adverse events include: diarrhea (3.8%), rash (7.7%), constitutional symptoms (11.5%), and nausea (11.5%). Conclusion: The combination of gefitinib and docetaxel at 60 mg/m2 is tolerable, with interim results showing a median survival time of 4.4 mo at this point. If the protocol’s goal of median survival time of 5.25 mo is met upon study completion, the combination may be worthy of further investigation. No significant financial relationships to disclose.