bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant treatment for rectal cancer in fit and vulnerable patients older than 70 years
Authors: Friso M. L. , Pasetto L. M. , Basso U. , Pucciarelli S. , Rugge M. , Agostini M. , Serpentini S. , Favaretto A. , Nitti D. , Monfardini S. 
Published: March 2020

13586 Background: To evaluate the toxicity and feasibility of neoadjuvant 5FU continuous infusion or bolus in combination with pelvic radiotherapy (RT) in rectal cancer patients older than 70 years. Methods: From June 2000 to June 2005, 36 patients older than 70 years out of a total of 300 consecutive cases with histologically proven locally advanced rectal adenocarcinoma (≤ 12 cm from the anal verge) classified as either T3 or T4, N0 or N1–2 M0 disease, were examined. Comorbidities were evaluated according to Cumulative Illness Rating Scale-Geriatric (CIRS-G) and patients were deemed “fit” if they were otherwise healthy or had one or more comorbidities of only grade 1; “vulnerable” if had one or more comorbidities of grade 2. Results: Median age was 74 years (range, 70–82). 14 patients (5 healthy, 13.8%, and 9 with slight comorbidities, 25%) were fit and 22 (61.2%) were vulnerable. All the patients received the full course of RT, with a total dose of 50.4 Gy. The mean number of chemotherapy weeks was 5.34 (range, 2–6). 4 out 14 (28.6%) fit patients and 9 out 22 (40.9%) vulnerable patients had to interrupt chemotherapy prematurely because of toxicity (p=0.26). Vulnerable patients did not experience superior toxicity compared to fit patients (8/22 vulnerable and 6/14 fit patients developed toxicities of grade ≥ 2, p=0.69). With the exception of 2 fit and 2 vulnerable patients who were lost to follow up before surgery, 32 patients (88.9%) were operated. Thirty cases (12/14 fit patients, 85.7%, and 18/22 vulnerable patients, 81.8%) were radically resected without relevant postoperative complications. 13/20 vulnerable and 10/12 fit patients had a pathological downstaging of disease (p=0.24). Conclusions: Selected vulnerable elderly patients with rectal cancer can receive the same neoadjuvant chemoradiotherapy and undergo surgery as well as fit elderly patients since tolerability and response rate seem to be similar in both categories of patients. No significant financial relationships to disclose.
Immunological relevance of the tumor associated antigen (TAA) COA-1 in colorectal cancer (CRC)
Authors: Corsi D. C. , Maccalli C. , Ciaparrone M. , Scinto A. F. , Cucchiara G. , Belardelli F. , Zagonel V. 
Published: March 2020

13590 Background: Immunotherapy (IT) in CRC has often produced discouraging results. COA-1 is a new TAA recognized by CD4+ T cells from peripheral blood (PB) of a CRC pt; its immunogenic epitope is presented on the surface of tumor cells in association with DRβ1*1301 or *0402 HLA class II molecules. Our aim is verifying whether an immune response directed against COA-1 mediated by CD4+ T cells can be isolated from PB of CRC pts. To achieve a more efficient anti-tumor response a recognition of a specific antigen by both the CD4+ and CD8+ lymphocytes should be performed; so different epitopes deriving from the processing of the same antigen should be presented to the immune system in association with both class I and class II MHC molecules. We identified a list of COA-1 derived peptides with the calculated score for the binding to HLA-A2, the more common HLA class I molecule within the Caucasian population. A failure in generating COA-1 specific T cells was observed in stage I-II CRC pts. Methods: From Jan 04 to day PB samples from 36 CRC pts (14 stage III/ 22 stage IV) have been collected and the HLA typing has been performed. Pts. expressing HLA DRbβ*0402, HLA DRβ1*1301 or HLA-A2 have been selected to collect other blood drawns and verifying whether an immune response directed against COA-1 could be isolated from their PB. Results: 4 pts were positive for the expression of DRβ1*1301 and 2 for the expression of DRβ1*0402. PB lymphocytes have been in vitro stimulated with the COA-1 derived epitopes and tumor reactivity has been verified. An immune response directed to COA-1 was detected in the PB of these 6 pts; anti-COA-1 CD4+ T cells were in vitro isolated and their cytotoxicity measured by granzyme B release. 9 pts were positive for the expression of HLA-A2 and we are stimulating the lymphocytes isolated from these pts with 6 selected COA-1 derived peptides binding the HLA-A2. We observed specific CD8+ T cells for 2 peptides in 1 pt. Conclusions: Our data identify COA-1 like an immunogenic antigen that can evoke an anti-tumor immune response CD4+ mediated in CRC; the response correlates with disease progression. Experiments are ongoing to evaluate an immune response mediated by both CD4+ and CD8+ T cells. These results will determine whether COA-1 could be used for future protocols of IT in CRC. No significant financial relationships to disclose.
5-fluorouracil (5-FU) plus cisplatin (CDDP) induction chemotherapy followed by combined external bean radiation therapy (XRT) and mitomycin-C (MMC) and 5-FU chemotherapy in locally advanced anal canal cancer (ACC)
Authors: Rodriguez-Riao J. J. , Figueira D. , Zarraga E. , Lion L. , Fuentes M. B. , Fernandez P. , Nasr I. , Gamboa C. , Ochoa J. 
Published: March 2020

14016 Background: Definitive chemoradiation therapy is the standard of care for squamous or cloacogenic cell ACC. The chemotherapy regimen comprising 5-FU and MMC is the most commonly used among patients with ACC, nearly 70% of patients can get complete response (CR), with the benefit of sphincter preservation, but patients with a large tumors (T3/T4) or nodal metastases have a response of 50%. Methods: To improve outcome, we conducted a phase II, study of 5-FU and CDDP followed by combined XRT plus 5-FU and MMC. Eligibility included patients withT3/T4 ACC with limited locoregional nodal involvement (N0/N1). Treatment: 5-FU 1000 mg/m2/days 1 to 5 in continuous i.v. infusion plus CDDP 100 mg/m2 i.v. day 1 q21d was administered for 2 cycles (weeks 1 and 4) followed by XRT (4.5 Gy) during 6 weeks (weeks 7 to12) with concurrent 5-FU 1000 mg/m2/days 1 to 4 in continuous i.v. infusion plus MMC 10 mg/m2 i.v. day 1 (weeks 9 and 17). RECIST criteria were used to assess tumor response Results: 59 patients were entered on this study from 8/2000 to 2/2005. Median age: 57 yrs (37–83), 49 F/10 M, median ECOG PS 0 (0–1), T3/T4 44/15, N0/N1 20/39. 54 patients were evaluable for clinical response: Induction chemotherapy led to 13 (24%) CR, 38 (70%) partial responses (PR) and 2 (6%) stable disease. After combined modality treatment, there were a total of 36 (67%) CR, 13 (24%) PR, 5 (9%) SD. Median follow up was 21.6 months (5–52).The median time to progression is 20.5 months (3–52). Toxicity grade 3/4: Neutropenia 20% (10/54), thrombocytopenia 13% (7/54), radiodermatitis 13% (7/54), nausea/vomiting 7% (4/54). Our previous experience with concurrent treatment without induction (n=27) resulted in a CR 59%, PR 37%, and 4% progressive disease Conclusions: We concluded that induction chemotherapy followed by combined XRT and chemotherapy could be an option in treatment of locally advanced ACC. No significant financial relationships to disclose.
Temozolomide/capecitabine therapy for metastatic neuroendocrine tumors of the pancreas. A retrospective review
Authors: Isacoff W. H. , Moss R. A. , Pecora A. L. , Fine R. L. 
Published: March 2020

14023 Background: Our laboratory studies suggest additive to synergistic cytotoxicity when neuroendocrine (NET) cells were given continuous exposure to 5 fluorouracil (5-FU) which preceded exposure to temozolomide (T). Based on this in vitro efficacy, salvage treatment with capecitabine (C), an orally-available fluoropyrimidine that is metabolized to 5-FU, and T was initiated in 17 patients (pts) with advanced NET of the pancreas. Methods: A retrospective review was conducted of the 17 pts who received C 1000mg bid on days # 1–14 and T 150–200mg/m2 on days #10–14 of a 28-day cycle, beginning in October, 2002. Pts had imaging performed after every 2 cycles, and serum tumor markers (TM), when present, were measured at every cycle. Median Age 54 (range 33–70). There were 9 men and 8 women. All of the pts had failed first-line treatment with escalating doses of sandostatin LAR. 11 pts had failed multiagent chemotherapy (range 1–5 regimens). Pathology: 10 pts had NET, 3 had non-secretory carcinoid, 1 had secretory carcinoid, one had a glucagonoma; 2 had non-secretory beta cell tumors and one pt had Multiple Endocrine Neoplasia Type I. Results: 13 of the pts are still alive and 12 remain on therapy with SD or PR. One pt did not complete cycle #1 and is not evaluable for response, but is included in an intent-to-treat (ITT) analysis. Grade 3 toxicity was thrombocytopenia in 2 pts, 1 of whom had splenectomy with resolution, and hand-foot syndrome in 1 pt who resumed therapy at reduced dose of C. Of 17 pts with unidimensionally measurable disease, 1 (6%) achieved a complete pathological response. 9 pts (53%) achieved a partial response by RECIST criteria, with a median duration of PR of 284 days (range 85–364 days). Of the 7 pts with evaluable TM, 6 (86%) had a greater than 50% decline. Median overall survival by ITT analysis in the 4 pts now deceased was 268 days (range 111–613 days). Median time to treatment failure was 340 days (range 111–470 days) in 5 pts. Conclusion: The results of this retrospective review suggest that a combination of T + C is active, well tolerated and may prolong survival and palliate symptoms in pts with NET. [Table: see text]
Gemcitabine, docetaxel, and capecitabine (GTX) in the treatment of metastatic pancreatic cancer (PC): A prospective phase II study
Authors: Fine R. L. , Fogelman D. R. , Sherman W. , Schreibman S. , Siegel A. , Mauer M. , Chen J. , Chu K. 
Published: March 2020

14024 Background: We have found that the combination of gemcitabine, docetaxel, and capecitabine (GTX), when administered in a specific sequence, will induce a p53 independent pathway of cell death through the MAP kinase pathway. The sequence overcomes drug resistance in PC cells in vitro. We have begun a prospective, phase II trial of GTX in patients with metastatic PC as first-line therapy. Methods: 23 patients with metastatic PC, ECOG 0–2 were enrolled at either Columbia or a community practice. Each cycle was administered over a 21 days. Capecitabine was administered at 750 mg/m2 twice daily for 14 days. Gemcitabine (750 mg/m2 over 75 minutes) and docetaxel (30 mg/m2) were administered on days 4 and 11. Responses were measured by CT (RECIST) and PET after every three cycles. A response by PET was defined as a 50% reduction in SUV while a CR was an absence of uptake. Results: Median age was 61, including 8 men and 15 women. Metastatic sites included liver (87%), abdomen (65%), and lung (17%). 70% of liver positive patients had at least five metastases. 22% had malignant ascites. 16 patients remain alive and 7 have progressive disease. Median survival has not yet been reached. Progression occurred at a median of 5.1 months. By CT, the response rate at metastatic sites was 39% (17% CR / 22% PR). Stable disease was observed in 48% at metastatic sites. PET showed a 53% response rate at metastatic sites. At the primary site, CT showed a 30% response rate including 17% complete responses. By PET criteria, there was a 31% response rate and a 26% CR rate at the primary site. In three patients, a PET response heralded a CT response by three cycles. In one patient, progressive disease on PET preceded progression on CT by two months. Toxicity: Grade 3 leukopenia and thrombocytopenia were 13% and 9%, respectively. There was no grade four hematologic toxicity. One patient experienced lung disease related to gemcitabine and withdrew from the study. A second patient experienced grade 4 mucositis, thrush, and sepsis which was presumed due to DPD deficiency. Grade 3–4 toxicities: HFS: 9%. There was no grade 3–4 diarrhea. Conclusions: GTX, elicits a promising response rate when used in metastatic P.C. PET detects a response and failure of chemotherapy earlier than CT scans. [Table: see text]
A phase II study of capecitabine and oxaliplatin (CAPOX) in metastatic adenocarcinoma of the small bowel (SBA) or ampulla of Vater
Authors: Overman M. J. , Chedid S. , Morris J. , Waldrum S. , Wolff R. A. 
Published: March 2020

14025 Background: Metastatic SBA and ampullary adenocarcinoma (AAC) are incurable, aggressive malignancies. Limited data exists regarding the role of systemic chemotherapy in these diseases. Given the marked activity of CAPOX in other cancers of the gastrointestinal tract, we have investigated the activity of this combination in these two tumor types. Methods: Patients (pts) with either metastatic or unresectable SBA and AAC who had adequate organ function, ECOG performance status (PS) ≤2 and measurable disease per modified RECIST criteria were enrolled. Prior use of 5-FU or capecitabine as adjuvant therapy, neoadjuvant therapy, or with radiation was allowed. CAPOX was administered as a 21 day cycle with oxaliplatin 130mg/m2 IV on day 1 and capecitabine 750mg/m2 PO BID days 1–14. Up to 30 pts will be enrolled. The primary endpoint is overall response rate (ORR). Results: Eleven pts have been enrolled from 11/04 to 12/05 (6 with AAC and 5 with SBA). Ten pts have received ≥2 cycles and are evaluable for response. All pts had metastatic disease and none had received prior chemotherapy. Patient (pt) characteristics: median age 59 (49–76); M/F (4/7); 91% PS 0–1. Grade 3/4 toxicities included fatigue (5), neuropathy (1), anorexia (1), thrombocytopenia (1), hypokalemia (1), hyponatremia (1), and musculoskeletal (1). Common grade 1/2 toxicities included neuropathy (8), nausea (8), diarrhea (6), and fatigue (5). Four pts required dose reduction and 1 pt discontinued due to toxicity (grade 3 fatigue). Six pts, 3 AAC and 3 SBA, responded with an ORR of 60% (95% CI 31 to 83%). Five responses have been confirmed and 1 AAC pt obtained a complete response after 5 cycles of treatment. Median time to progression was 6.8m (95% CI 4.4 to 9.3+m). Conclusions: The combination of CAPOX is both well-tolerated and highly active. The ORR of 60% is one of the highest yet reported in the literature for the treatment of adenocarcinoma of the small bowel and ampulla of Vater. Enrollment continues on this trial. (Supported by a research grant from Sanofi-Aventis). [Table: see text]
Patient tolerance of palliative chemotherapy for recurrent hepatocellular carcinoma following orthotopic liver transplant
Authors: Sobol A. L. , Kuriakose P. , Colon-Otero G. 
Published: March 2020

14034 Background: While orthostatic liver transplant (OLT) is an accepted treatment for localized hepatocellular carcinoma (HCC), little data exists as to the appropriate treatment of recurrent disease. Consensus opinion favors avoiding systemic chemotherapy on the grounds that toxicity would be poorly tolerated by patients medically immunosuppressed to prevent allograft rejection. Methods: Study design: retrospective chart review. The medical records of all patients who underwent OLT at the Mayo Clinic in Jacksonville, Florida, from February 1998 to April 2005 were reviewed. Those patients who developed recurrent HCC treated with systemic chemotherapy and were followed for at least 5 weeks with documented side effects were identified as the study population. Tolerance of treatment was assessed through review of side effects and Eastern Co-operative Oncology Group (ECOG) performance status scores. Disease progression was identified as increasing size of lesions on computed tomography (CT) scans and increasing serum alpha fetoprotein (AFP) levels. The primary endpoint was defined as discontinuation of chemotherapy due to severe side effects. Results: Of 1133 patients undergoing OLT, 179 were diagnosed with HCC. Thirty developed recurrent disease. Of these, 8 did not receive chemotherapy (2 observation only, 2 Hospice care, 2 radiation therapy, 1 surgical resection, 1 chemoembolization), 10 were lost to follow-up, and 2 died of rapidly progressive disease. The remaining 10 patients underwent systemic chemotherapy with six patients receiving multiple regimens. Seven patients received from 2 to 15 cycles of gemcitabine and cisplatin. Cytopenias were the most common side effect. One patient discontinued the regimen after developing neutropenic fever following 2 cycles of treatment. Five patients received from 1 to 12 cycles of capecitabine. Diarrhea was the most common side effect. Three patients received from 3 to 6 cycles of doxorubicin. Stomatitis and cytopenias were the most common side effects. No treatment related mortalities were observed. Conclusions: Palliative systemic chemotherapy is not usually associated with life threatening side effects and therefore is a viable option for patients with recurrent HCC following OLT. No significant financial relationships to disclose.
A phase I clinical and pharmacokinetic study of escalating doses of fixed rate and escalating infusion duration of gemcitabine given via an intrahepatic pump for patients with hepatic metastases
Authors: Tse A. N. , Raggio G. , Morse M. , Kemeny N. E. 
Published: March 2020

14035 Background: Gemcitabine (Gem) is an attractive chemotherapeutic agent for hepatic arterial infusion (HAI) because of its broad-spectrum anti-tumor activity, high systemic clearance, and possibly high hepatic extraction. Pre-clinical models indicate that cytotoxicity of gemcitabine increases with duration of drug exposure. Methods: In this phase I trial, successive cohorts of patients (Pts) with hepatic metastases of colorectal or bile duct cancer were given HAI Gem 3 out of 4 weeks. During the dose escalation phase, increasing doses of HAI Gem (800, 1000, 1200 and 1500 mg/m2) were given at 10 mg/m2/min. During the infusion duration escalation phase, 1000 mg/m2 of HAI Gem was given over increasing duration of infusion (200, 300, and 400 min.). To compare the pharmacokinetics of HAI Gem with that of intravenous (iv) Gem, Pts enrolled to the infusion duration escalation phase received a 60-min. infusion of iv Gem during the first treatment week at the same dose-rate as with subsequent HAI Gem. Results: To date, 23 Pts have been enrolled and 22 were evaluable for toxicity (median age 64; median KPS 90%; 13 males/9 females). All Pts had prior HAI FUDR treatment. HAI Gem is well tolerated up to 1500 mg/m2 given at 10 mg/m2/min and up to 1000 mg/m2 infused over 300 min. Only one Pt had to discontinue therapy due to toxicity (grade 4 alkaline phosphatase) and one DLT was observed (grade 3 rash). Most common grade 2+ toxicities include neutropenia (40%), thrombocytopenia (23%), bilirubin (14%), and alkaline phosphatase (23%). The steady-state level of Gem when given by HAI was lower than that obtained when the drug was given by iv in 3 out of 4 Pts (0.62 vs 1.8; 0.38 vs 2.9; 0.36 vs 0.63 mcg/ml). One Pt with cholangiocarcinoma had a partial response and one Pt had stable disease for 5 months. Conclusions: HAI Gem is safe and can be given as prolonged infusion not achievable with systemic administration. Pharmacokinetic studies indicate good hepatic extraction of the drug. The MTD has not been reached. [Table: see text]
Expression of epidermal growth factor receptor (EGFR) associates with proliferation, apoptosis, and histologically aggressive features in hepatocellular carcinoma
Authors: Morinaga S. , Nakamura Y. , Sugano N. , Tsuchida K. , Shiozawa M. , Miyagi Y. , Akaike M. , Sugimasa Y. , Takemiya S. 
Published: March 2020

14039 Background: Epidermal growth factor receptor (EGFR) is over-expressed in many types of cancers, plays an important role in the tumorigenesis, and is indicated to be a promising target for cancer therapy. Hepatocellular carcinoma (HCC) is a cancer with one of the worst prognosis, and new therapeutic approaches are required. The aim of this study was to clarify a possible role of EGFR expression on clinico-pathology of HCC. Methods: HCC tissues were obtained from 36 HCC patients (23 men and 13 women, range 45–80 years old) who underwent curative surgery. EGFR status of the tumors was assessed by immunohistochemical (IHC) analysis on formalin-fixed paraffin-embedded tissue. The percentage of positive tumor cells was scored as follows: 0+, no positive tumor cells; 1+, 1–10% positive cells; 2+, 10–50% positive cells; 3+, >50% positive cells. The staining intensity of membrane was evaluated as follows: 0+, negative; 1+, weak; 2+, moderate; 3+, strong. A composite score (EGFR score) was obtained by calculating the sum of these two scores. The tumor cell proliferation and apoptosis were assessed with Ki-67 labeling and ssDNA labeling, respectively. Results: EGFR expression was detected in 33 (91.7%) of 36 tumors. EGFR score ranged from 0 to 6. Higher EGFR score was related with poorer histologic grade (P = 0.005 by Kruskal-Wallis) and advanced pathologic stage (P = 0.038 by Kruskal-Wallis). EGFR score correlated positively with Ki-67 labeling indices (r = 0.358 and P = 0.032 by Spearman), and correlated negatively with apoptosis indices (r = −0.388 and P = 0.019 by Spearman). EGFR score did not affect disease free survival (DFS) or over all survival (OS), after curative surgery. Conclusions: Higher expression of EGFR, assessed with IHC, associates with more aggressive pathologic features, increased tumor cell proliferation, and reduced tumor cell apoptosis. However, further examination is needed to clarify its predictive significance. No significant financial relationships to disclose.
Phase II study of PS-341 (bortezomib) with or without irinotecan in patients (pts) with advanced gastric adenocarcinomas (AGA)
Authors: Ocean A. J. , Schnoll-Sussman F. , Keresztes R. , Chen X. , Holloway S. , Matthews N. , Christos P. , Mazumdar M. , Wright J. , Wadler S. 
Published: March 2020

14040 Background: We are conducting a phase II trial of the proteasome inhibitor, PS-341, with or without irinotecan in pts with AGA. The combination of PS-341 and irinotecan has been studied in preclinical tumor models including a murine xenograft model of colon cancer, where the combination achieved significantly more tumor shrinkage than either agent alone. The primary objective of this study is to determine response rates, toxicities, progression-free survival, and overall survival in pts with AGA receiving PS-341 alone or in combination with irinotecan. Methods: All pts had gastric adenocarcinoma beyond the scope of surgical resection, measurable disease, and normal bone marrow, hepatic and renal function. All gave informed consent. In previously untreated patients, PS-341 was administered at 1.3 mg/m2 on days 1, 4, 8, and 11 as IV bolus every 21 days. Irinotecan was administered IV at 125 mg/m2 over 90 mins on days 1 and 8 every 21 days (Arm A). For previously treated patients, PS-341 was administered as a single agent at 1.3mg/m2 on days 1, 4, 8, 11 as an IV bolus every 21 days (Arm B). Radiologic evaluation and tumor measurements were performed every 8 weeks. Results: Thirty-seven pts have been enrolled; 29 are evaluable (4 never treated, 4 TETE). Twenty-two pts were treated in Arm A, and 11 in Arm B. All pts were eligible and the 29 treated pts were fully evaluable. Median age 58 (33–87); 26 males/7 females; median number of cycles received was 2.0. Most common toxicities: Grade 4 cardiac arrest (1), stomach perforation (1), leukopenia (2), diarrhea (1), edema (1); Grade 3 nausea (6), vomiting (7), diarrhea (4), febrile neutropenia (3), thrombocytopenia (6), anemia (6); Grade 5 death (3). Severe toxicities likely attributed to disease progression. Response rate was 33% for Arm A, 9% for Arm B. Progression-free survival was 1.8 mo. in Arm A, 1.4 mo. in Arm B. Median overall survival was 4.8 mo. in Arm A, 5.4 mo. in Arm B. Conclusions: The combination of PS-341 and irinotecan, a non-cisplatin containing therapy, is active in AGA and should be considered a key regimen. Monotherapy with PS-341 has a 9% response rate in this population of pre-treated patients with advanced disease. Accrual to this study is continuing. [Table: see text]