bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fixed dose rate (FDR) gemcitabine (G) and capecitabine (C) in patients with metastatic biliary tract cancer (BTC): Final results of phase II trial
Authors: Santini D. , Vincenzi B. , Vasile E. , Catalano V. , Virzì V. , Masi G. , Intagliata S. , Catalano G. , Falcone A. , Tonini G. 
Published: August 2020

e15510 Background: The combination of fixed dose rate (FDR) gemcitabine (C) and capecitabine (G) has been demonstrated to be well tolerated in patients with advanced cancers. To determine the activity and safety of this combination in metastatic metastatic biliary tract cancer patients, a phase II trial was conducted. Methods: Patients with unresectable BTC who had pathologically confirmed adenocarcinoma, no prior chemotherapy, ECOG PS < 2 and measurable disease were enrolled. Treatment consisted of FDR G at 800 mg/m(2) infused in 80 minutes on days 1 and 8 every 21 days with C administered orally bid in equal doses (650 mg/m2 bid) for 14 days (28 doses). Results: Between Feb 2005 and Sept 2008, 30 pts were enrolled. Median age was 67 (45–86) with 14 males. 30 pts were evaluable for response and toxicity. A total of 219 cycles were administered (median, 8; range, 2–16). One patient achieved CR and 8 pts achieved PR giving an overall response rate of 30.0% in intention-to-treat population (95% CI, 19.2–42.6%). And 11 pts (36.6%) had stable disease. The median time to progression of all patients was 7.4 months (mo) (95% CI, 3.2–19.5). The median overall survival was 15.3 mo (95% CI, 4.6–27.9). Grade 3/4 neutropenia and thrombocytopenia were noted in 13.3% and 6.6% of the pts, respectively. Grade 2/3 non-hematologic toxicities were asthenia (50.0 % of pts), diarrhea (16.6%), stomatitis (23.3%) and hand-foot syndrome (6.6%). There was no treatment-related death. Gemcitabine was skipped at least once/reduced in 20%/15% of the patients, respectively. Capecitabine was skipped at least once/reduced in 20%/25% of the patients, respectively. Conclusions: The combination of FDR gemcitabine and capecitabine in this three week cycle is safe and seems to have advantages in activity over other regimens in advanced biliary cancer. No significant financial relationships to disclose.
Efficacy and tolerance of chemotherapy with dacarbazine or temozolomide associated or not with 5-fluorouracil (5-FU) in endocrine carcinomas: A retrospective multicentric study from the Groupe des Tumeurs Endocrines (GTE)
Authors: Pecout S. , Baudin E. , Paoli A. , Maire F. , Terrebonne E. , Mitry E. , Pavel M. , Ruszniewski P. , Cadiot G. , Brixi-Benmansour H. 
Published: August 2020

e15523 Background: Small studies have shown that therapy with dacarbazine and temozolomide give up to 34% tumoral response rates in endocrine carcinomas. The aim of this large retrospective multicentric study was to evaluate efficacy and tolerance of chemotherapy with dacarbazine or temozolomide associated or not with 5-FU in endocrine carcinomas. Methods: Patients were recruited in 6 French and 1 German centers. All patients with well (WDEC) or poorly-differentiated endocrine carcinoma (PDEC), whatever the primary, and who have been treated with dacarbazine or temozolomide associated or not with iv 5-FU or capecitabine, were included. Response rates were evaluated according to RECIST criteria by one of the investigator and toxicity according to National Cancer Institute Common criteria. Results: 86 patients were included : 36 women, median age 61.7 years (27.7 - 85.7), 67 WHO-PS 0–1. Primaries were : pancreas (n=34), digestive tract (n=23), thyroid (n=9), lung (n=6), other (n=6), unknown (n=8). 64 patients had WDEC and 11 PDEC (11 not determined). The number of previous systemic treatments (chemotherapy, chemoembolization, radionuclide therapy) was: 0 (n=16), 1 (n=25), 2 (n=25), 3 (n=14), 4 and more (n=6). Treatments received were : dacarbazine (n=3), temozolomide (n=19), dacarbazine + 5-FU (n=48), temozolomide + capecitabine (n=16). Evaluation was impossible in two patients. Tumoral response rates (partial and stabilization) were 61.2% in WDEC and 18.2% in PDEC. The best response rates in WDEC were : partial response (n=6; 9.7%), stabilization (n=32; 51.6%), progression (n=24; 38.7%) without significant differences between regimens and primary location. Response rates in WDEC were 88.9%, 71.4% and 64.7% in first, second and third line therapies, respectively. Median progression free survival in WDEC was 5.7 months (0.1–41.7). Grade 3–4 toxicities were hematologic (n=8), digestive (n=10), infection (n=3). Conclusions: Dacarbazine and temozolomide therapy showed high partial response and stabilization rates up to 3rd line therapy in well-differentiated endocrine carcinoma, with moderate toxicity. MGMT tumoral status is currently investigated. No significant financial relationships to disclose.
Phase I dose escalation study of pomalidomide in combination with gemcitabine in patients (pts) with untreated metastatic carcinoma of the pancreas
Authors: Infante J. R. , Jones S. F. , Bendell J. , Spigel D. , Barton J. , Zubkus J. , Byrne C. , Griner P. , Weekes C. , Messersmith W. A. , Burris H. A. 
Published: August 2020

e15539 Background: Pomalidomide is an IMiD immunomodulatory compound that is synergistic with gemcitabine in preclinical models. Pomalidomide has immuno-stimulatory properties and effects on the tumor microenvironment including inhibition of inflammatory mediators, stromal cell support, endothelial cell function, and angiogenesis. The primary objective is to determine the maximally tolerated dose (MTD) and evaluate the safety profile of pomalidomide in combination with gemcitabine. Methods: Eligibility included pts with untreated metastatic pancreatic cancer, adequate organ function, ECOG 0–1, and willingness to take prophylactic anticoagulation with aspirin, low-dose coumadin, or low molecular weight heparin. Gemcitabine 1,000 mg/m2 was given as a 30 min IV infusion on days 1, 8, and 15 of a 28 day cycle. Pomalidomide was given orally, daily for 21 days of a 28 day cycle. 3–6 pts were enrolled to increasing dose cohorts of pomalidomide (2, 3, 5, 7, and 10 mg/day) until dose-limiting toxicity (DLT) was seen in ≥2 of 6 pts. Results: As of 15-Dec-2008, 22 pts received ≥ 1 dose of pomalidomide. No DLT's were observed for 2–7 mg and 3 pts are currently on study in the 10 mg cohort. Neutropenia occurred in 12 pts, 8 were grade 3–4 events. There was 1 DLT of grade 3 neutropenic fever in the 10mg cohort. Thrombocytopenia events (9) were grade 1–2. Non- hematologic events were grade 1–2, the most common being rash (11), fatigue (10), nausea (6), and diarrhea (6). The rash is mild, erythematous, nonpruritic, of limited distribution, and reversible. 2 pts developed DVT (1 during cycle 2 and 1 cycle 4). Of the 16 pts evaluable for response, 1 pt has a confirmed PR and a CA 19–9 that normalized from 157 to <3. 4 additional pts have had minor radiographic responses between 10 and 29%. 10 of 16 pts have had a ≥ 60% decrease in CA19–9 from baseline. Only 2 pts came off study for early progression at the end of cycle 2. Conclusions: Dosing of pomalidomide daily for 21 days in combination with gemcitabine 1,000 mg/m2 given IV on day 1, 8, and 15 of a 28 day cycle was well tolerated and has promising clinical activity in patients with metastatic pancreatic cancer. The RP2D of pomalidomide in combination will be 7 or 10 mg. [Table: see text]
Phase II trial of second-line chemotherapy in metastatic pancreas cancer with the combination of oxaliplatin (Ox) and capecitabine (Cp)
Authors: Gasent Blesa J. , Alberola Candel V. , Giner Marco V. , Juan O. , Provencio Pulla M. , Llorca C. , Gravalos C. 
Published: August 2020

e15561 Background: Gemcitabine (G) based chemotherapy is the standard treatment for patients (Pt) with pancreatic cancer. In spite of an active first line chemotherapy, second-line chemotherapy treatment is yet an unmet medical need. Ox and Cp have shown activity in different settings of the disease. We performed this prospective phase II trial to evaluate the efficacy and safety of the combination of Ox and Cp in second-line pancreatic cancer chemotherapy. Methods: From May 2007 to October 2008 15 Pt PS0–2 were included. All Pt had received G 1000 mg/sqm D1, D8 and D15 every 28 days as adjuvant (2 Pt) or first- line therapy (13 Pt). Gender: male/female 8/7, mean age was 64.1 years (47–82), in Pt with elevated CA-19.9 at diagnosis mean CA-19.9 was 337.6 (47–689). Mean time from diagnosis to initiation of second line chemotherapy was 219.3 days (121–457). Metastases (Mt): 11 liver Mt and 8 Pt liver and other Mt sites. Mean number of G cycles received was 6.8 (3–14). All Pt ended G treatment because of disease progression. After progression, all patients received second-line chemotherapy consisting of Ox 100 mg/sqm D1 and Cp 1000 mg/sqm bid D1-D14, every 21 days (XELOX). Results: Median number of cycles of XELOX administered was 4.5 (1–16). Mean CA-19.9 at start of second-line chemotherapy was 714.6 UI/ml (154–1536). Best radiological response was: complete response 1 Pt, stable disease 5 Pt, progressive disease 9 Pt. Median PFS was 124 days (21–480, censored data). Median OS was 301 days (censored data; 150–760). Median survival since the beginning of second line chemotherapy, was 163 days (censored data). In the responding-stable disease patients CA 19.9 level at the beginning of the chemotherapy changed from a median of 241 UI/ml (67–457) to 44.26 (9–86) at the last evaluation with a median decrease of 81.5 %(72–88%). Reported toxicity was the following: Diarrhea G1 in 1 Pt and G2 in 1 Pt, paresthesia G1 in 2 Pt, and hematological toxicity G1 in 1 Pt. Conclusions: As a second-line therapy after standard G treatment, XELOX offers clinical activity that warrants further investigation in this unmet medical need. No significant financial relationships to disclose.
A retrospective analysis of tumor size (TS) as a continuous rather than discrete variable in advanced pancreatic cancer
Authors: Dhani N. C. , Tu D. , Parulekar W. , Seymour L. , Moore M. J. 
Published: August 2020

e15565 Background: Objective “response rate” (RR) dichotomizes patients into categories of “response” (complete or partial) and “non-response”. This ignores a lot of data captured within the trial on tumor size changes, and may miss clinically important effects on tumor growth may occur in the absence of a response. Analyzing TS as a continuous variable (TS-CV) has been suggested as a more robust indicator of efficacy. Methods: Tumor size data from 2 randomized controlled trials in advanced pancreatic cancer conducted by NCIC.CTG were analyzed; NCIC.PA1 randomized patients to BAY12–9566 (MMPI) or Gemcitabine (Gem) and demonstrated a large and significant survival (OS) benefit for Gem (6.7 vs 3.4 months), NCIC.PA.3 randomized patients to Gem ± Erlotinib and showed a modest OS benefit for the combination (HR =0.81). In PA1, an early interim analysis (IA) using absence of progression as the primary measure did not halt accrual. Measures of TS at baseline and 8 wks were transformed and represented as a logarithm of the sum of the longest diameters. The difference in logarithms (d-LTS) from baseline to 8 weeks was calculated to indicate change in tumor size. Groups were compared using Wilcoxon rank-sum test. Results: In PA1, TS was significantly decreased in the Gem arm (mean d-LTS 0.087 on MMPI vs. -0.066 on Gem; p<0.0001), in keeping with the OS benefit (p<0.001). The decrease was also significant in the interim analysis cohort (p=0.007) and this result would, if used, have halted accrual earlier. In PA3, for all patients, decrease in TS was significantly larger for the combination arm (mean d- LTS -0.148 on combination vs. -0.114 on Gem; p=0.04), consistent with the OS benefit (p=0.038). Analysis on the 1st 130 patients yielded similar results (p=0.02) Conclusions: Tumor size changes may be a reasonable endpoint for screening efficacy trials in advanced pancreatic cancer. These results support further assessment of this alternate efficacy endpoint. No significant financial relationships to disclose.
A phase II trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent external-beam radiotherapy for locally advanced pancreatic cancer
Authors: Shinchi H. , Maemura K. , Mataki Y. , Kurahara H. , Natsugoe S. , Takao S. 
Published: August 2020

e15570 Background: S-1 is a new oral fluoropyrimidine anticancer agent and has shown a good efficacy for pancreatic cancer. In the phase I trial, we evaluated the safety of S-1 combined with external-beam radiotherapy (EBRT) to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients (H. Shinchi et al,, Br J Ca 2007;96:1353). The phase I trial determined the recommended of S-1 for the phase II chemoradiotherapy trial to be 80mg/m2/day given on days 1–21. This phase II trial was conducted to evaluate the efficacy and toxicity of EBRT combined with S-1 for locally advanced pancreatic cancer. Methods: Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, ECOG PS 0–1, adequate organ and marrow function, and no prior anticancer therapy. EBRT was delivered in fractions of 1.25Gy twice daily, totaling 50Gy per 40 fractions for 4 weeks. S-1 was given orally at a dose of 80mg/m2/day twice a day on days 1–21. The primary end-point of this trial was objective tumor response and secondary end-points included toxicity and overall survival. Results: Forty patients were enrolled in this phase II trial. Of the 40 patients, 39 (97%) completed the scheduled course of chemoradiotherapy. The objective tumor responses by RECIST criteria included 13 PR (33%), 20 SD (50%) and 7 PD (17%). The median survival time was 14 months and 1-year survival rate was 67%. Although grade 3 rash and anorexia occurred in one patient each, no grade 4 toxicities were observed. Conclusions: Combination therapy of S-1 and radiation shows favorable efficacy for locally advanced pancreatic cancer and was well tolerated with no severe toxicities. No significant financial relationships to disclose.
Comprehensive analysis of Excision repair complementation group 1, Glutathione S-transferase, Thymidylate synthase, and Uridine diphosphate glucuronosyltransferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI
Authors: Kim H. , Seo B. , Kim J. , Oh S. , Lee S. , Kim S. , Kwon H. 
Published: August 2020

e15580 Background: Pharmacogenetic advances in cancer chemotherapy have the potential to predict clinical benefit to particular regimens. Oxaliplatin and irinotecan have shown to be effective in the treatment of gastric cancer. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, GST, TS, and UGT1A1predicted overall survival in gastric cancer patients receiving FOLFOX and/or FOLFIRI chemotherapy. Methods: Total genomic DNA was extracted from whole blood of patient. The PCR- restriction fragment length polymorphism (RFLP) method was applied to detect the known variant sites of ERCC1, GST, TS, and UGT1A1. Results: Response rate of FOLFOX (N=75) was 24%. Grade 3–4 neutropenia and neurotoxicity were observed 34.7% and 16%, respectively. TTP and OS of 1st line administration of FOLFOX (N=35) was 3.1 months (95% CI, 0.1–6.1 months) and 13.9 months (95% CI, 12.2–15.6 months). Only the GSTM1 positive genotype showed a significantly better time to progression (P=0.023). But significant genotype variation of TS, GST and ERCC1,which assumed to affect to activity of oxaliplatin was not observed to RR, toxicity, and overall survival. Response rate of FOLFIRI (N=74) was 23%. Grade 3–4 neutropenia and diarrhea were observed 55.4% and 9.5%, respectively. TTP and OS of 1st line administration of FOLFIRI (N=33) was 4.9 months (95% CI, 3.5–6.4 months) and 19.0 months (95% CI, 8.5–29.5months). Low expression type (2R/2R, 2R/3C, and 3C/3C) of TS was associated with high incidence of grade ≥3 neutropenia. But significant genotype variation of UGT1A1,which assumed to affect to toxicity of irinotecan was not observed to RR, toxicity, and survival. Conclusions: In this study, GSTM1 positive genotype showed a significantly better time to progression in the advanced gastric cancer treated with FOLFOX. Low expression type (2R/2R, 2R/3C, and 3C/3C) of TS was associated with high incidence of grade ≥3 neutropenia in the advanced gastric cancer treated with FOLFIRI. Well designed prospective trial will be clearly identifying relations between chemotherapy and genetic variations. No significant financial relationships to disclose.
Downsizing after palliative systemic chemotherapy with weekly high-dose 5-fluorouracil (5-FU) as a 24h-infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with metastatic adenocarcinomas of the stomach or the gastro-esophageal junction followed by secondary metastatic resection
Authors: Koucky K. , Boxberger F. , Albrecht H. , Maennlein G. , Wolff K. , Ostermeier N. , Schildberg C. , Golcher H. , Hohenberger W. , Hahn E. G. , Wein A. 
Published: August 2020

e15585 Background: Due to the positive experience with combined AIO plus irinotecan (iri.) in a phase II trial (Möhler M et al, Br J Cancer 2005), this combination has been applied as first-line treatment in our department since 1999. Methods: 76 chemonaive patients (pts.) with histologically proven metastatic adenocarcinomas of the stomach or AEG tumours (tum.) (UICC IV), deemed to be non-resectable by the Interdisciplinary Tumour Board (ITB), were enrolled from 08/99 to 12/08. Chemotherapy (chemoth.) schedule: iri. (80 mg/m2 i.v. as 1h-infusion (inf.); d1, 8, 15, 22, 29, 36, qd 57) followed by 5-FU (2000 mg/m2 i.v.) with sodium folinic acid (500 mg/m2; d1, 8, 15, 22, 29, 36, qd 57) as 24h-inf. via port-a-cath. After downsizing the patients were again presented at the ITB. In 16 out of 76 pts. (21%) a secondary (sec.) metastatic resection (res.) with curative intent was taken into account. This collective is presented here evidencing the efficacy of this interdisciplinary procedure in palliative (pall.) treatment of gastric cancer. Results: Last date of evaluation: Dec/31/2008; median age: 58,7 years; men/women: n=12/4; res. of the primary tum. prior to pall. chemoth.: yes/no: n=2/14, ECOG 0/1: n=5/11; primary tum. localisation: AEG tum.: n=7; gastric carcinoma: n=9, elevated CEA yes/no: n=5/11, elevated CA19–9 yes/no: n=5/11. Number of metastatic localisations: 1/2/3: 69%/19%/12%, chemoth. application: total number:267; average value/patient:17 cycles altogether: 46, median cycles/pt.: 3, higher grade tox. (grade 3–4): anaemia 4%; diarrhea 2%, vomitus 2%, fever/infection 2%; response: PR 32%; SD 56 %; PD 6%; not evaluable 6 %; tum. control (PR, SD) 88 %; sec. res.: R0: 82 %; R1: 6 %, R2: 6 %; RX: 6%; gastrectomy with peritonectomy (R0): n=4 (25%), gastrectomy with lymph node dissection (D4,R0): n=6 (38%); HIPEC: n=4 (25%); 1-year survival:81%, 2-year survival: 44%, 3-year survival: 25%; deceased pts.: n=9 (56%), NED 19% (n=3). Conclusions: In our trial curative resections could be achieved in 82 % of the pts. During a follow-up of 20 months a NED status could be documented in 19% of the patients. No significant financial relationships to disclose.
A retrospective review of squamous cell carcinoma of the anal canal in HIV-positive and HIV-negative patients
Authors: Hammad N. , Philip P. A. , Shields A. F. , Heilbrun L. K. , Venkatramanamoorthy R. , El-Rayes B. F. 
Published: August 2020

e15586 Background: Human immunodeficiency virus (HIV) infected patients (pts) are at increased risk for squamous cell carcinoma of the anal canal (SCCAC) and the incidence of SCCAC has increased in the era of HAART (highly active antiretroviral therapy). The outcome of SCCAC in HIV (+) pts has not been evaluated in prospective trials and the published literature is limited to small retrospective case series. The aim of this study is to describe the outcome, tolerability, and overall survival (OS) in pts with and without HIV infection treated at Karmanos Cancer Institute, at Wayne State University from 1991 to 2007. Methods: We performed a retrospective chart review. We collected data regarding HIV status, demographics (age, gender, race), stage at diagnosis, treatment, response to treatment, toxicity, and survival. Results: Fifty pts with SCCAC were identified, of whom 18 were HIV (+) and 32 were HIV (−), 26% Caucasians, 68% African American, 56% males and 44% females. HIV (+) pts had significantly better stage (p = 0.011) and less frequent reduced chemotherapy dose (p = 0.001). There were no significant differences by HIV status in type of chemotherapy received, frequency of reduced radiotherapy dosage, use of diverting colostomy, or frequency of relapse. Diverting colostomy was required in 29% of HIV (+) pts and 18% of HIV (−) pts. The major toxicities observed in HIV (+) and (−) pts were diarrhea (36% vs. 64%), neutropenia (27% vs. 21%), and skin toxicity secondary to radiotherapy (XRT: 82% vs. 100%; p = 0.034). Median (OS) was 62.6 months for HIV (+) pts and 71.8 months for HIV (−) pts (p = 0.787). Conclusions: HIV (+) pts had better stage, received standard chemotherapy dose more often, and had more frequent XRT dermatitis than HIV (−) pts. Otherwise, there was no major difference in treatment toxicities. A higher proportion of HIV (+) pts required diverting colostomy. Survival is somewhat shorter among HIV (+) patients. No significant financial relationships to disclose.
Association of gender, age, and ethnicity with survival in patients with pancreas cancer
Authors: Ottochian M. , Yang D. , El-Khoueiry A. , Iqbal S. , Pohl A. , Zhang W. , Ning Y. , Lenz H. J. 
Published: August 2020

e15587 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. However little is still known about factors that influence its development and progression. Recent data suggest that PC is, at least in part, an estrogen- dependent disease; there is growing epidemiological evidence that aspects of reproductive history and hormonal exposure are associated with risk of this disease. It was shown that age at menarche of <13 is associated with less risk of PC. However no data are available whether gender is associated with outcome in patients with PC. The purpose of this study was to test whether age, gender or ethnicity influence the outcome in PC. Methods: The data of the 50,302 adults diagnosed with PC between 1988 and 2004 were extracted from the Surveillance Epidemiology and End Results public use database. These included 24,240 patients diagnosed with localized pancreatic cancer (LPC) and 26,062 patients with metastatic pancreatic cancer (MPC). Demographic, clinical variables and survival time were retrieved. The primary endpoint was overall survival. We constructed Cox proportional hazards models to evaluate association between patient characteristics and survival in LPC and MPC separately. Pair interactions were also tested. Results: On multivariate analysis gender, age, race, marital status, tumor size, grade, histology, type of treatment and lymph node involvement were found to be independent predictors of survival. Females had a significant longer survival, with an HR of 0.959 (95% CI: 0.932–0.987) among patients with LPC and an HR of 0.918 (95%CI: 0.894–0.942) among patients with MPC. Each age group displayed a significant longer survival than its correspondent older age group. When we combined age and gender in the analysis, females had a longer survival than males in each single age group in the MPC group. In the LPC group the longer survival of female patients was only observed in the youngest age group. Conclusions: This is the first and largest study to address gender and outcome in PC. Our data suggest that the estrogen pathway may play an important prognostic role in patient with this disease. These data also warrant further in vitro and in vivo investigations on the mechanisms of estrogen and pancreas progression. No significant financial relationships to disclose.