bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of 5-FU versus capecitabine in combination with mitomycin or cisplatin in the treatment of anal cancer.
Authors: Yu Irene S. , Cheung Winson Y. 
Published: March 2017

680 Background: Capecitabine is used as an alternative fluoropyrimidine to infusional 5-FU in the non-operative management of anal cancer due to its ease of administration. However, its patterns of use and long-term outcomes in the real world are poorly described. Our objectives were to determine the frequency of capecitabine use, compare the difference in outcomes, and examine the difference in treatment-related adverse events between oral and intravenous fluoropyrimidines. Methods: All anal cancer patients who received either capecitabine or infusional 5-FU as part of their curative intent chemoradiotherapy from 2010 to 2013 at any 1 of 6 comprehensive cancer centers in British Columbia were included. Chi-square and Wilcoxon-Mann tests were used to assess for associations between treatment groups and clinical characteristics and outcomes. Results: A total of 237 patients were identified; median age was 59 (IQR 53-67) years, 71 (30%) were men, 202 (85%) had ECOG 0/1, and 12 (5%) were HIV positive. Median total radiation dose was 54 cGy (IQR 50.4-54.0) and 21 (9%) underwent a colostomy prior to chemoradiation. Baseline characteristics were balanced between the two groups with respect to age, gender, ECOG, and HIV status (all p > 0.05). Overall, 155 patients (65%) received capecitabine. Comparing patients who received capecitabine vs 5-FU, overall (69% vs 74%, p = 0.388) and disease-free survival rates (68% vs 71%, p = 0.637) at 5 years from diagnosis were similar between treatment groups. There were no differences with respect to rates of subsequent colostomy (16% vs 23%, p = 0.185) and abdominoperineal resection (11% vs 12%, p = 0.777). However, patients who received capecitabine were less likely to report adverse effects (51% vs 26%, p < 0.001) than those who underwent 5-FU. The capecitabine group had a lower incidence of stomatitis (6% vs 40%, p < 0.001) whereas the 5-FU cohort reported less frequent hand-foot syndrome (1% vs 8%, p = 0.036). Conclusions: This population-based study demonstrates a preference for capecitabine use in place of 5-FU in the curative management of anal cancer. Survival outcomes are similar between the two treatment groups, but capecitabine may be better tolerated.
Safety and efficacy of regorafenib post-marketing surveillance (PMS) in Japanese patients with metastatic colorectal cancer (mCRC).
Authors: Komatsu Yoshito , Muro Kei , Yamaguchi Kensei , Satoh Taroh , Uetake Hiroyuki , Yoshino Takayuki , Nishida Toshirou , Takikawa Hajime , Kato Takeyuki , Chosa Masayuki , Sunaya Toshiyuki , Yamamoto Yuka , Hamada Yoko , Watanabe Toshiaki , Sugihara Kenichi 
Published: March 2017

721 Background: The oral multikinase inhibitor regorafenib (REG) was approved for unresectable mCRC in Japan in 2013 based on the results of the global CORRECT phase 3 trial, which included 100 Japanese patients (pts). A PMS (NCT01843400) was conducted to assess the safety and efficacy of REG for the treatment of Japanese mCRC in clinical practice. Methods: Pre-registration was applied in the PMS. Adverse events (AEs), laboratory tests, drug exposure and anti-tumor effects were prospectively monitored for 6 months after initiating REG. One-year survival data was also collected. Target enrollment was 1,250 pts. Results: 1,303 pts were enrolled from March 2013 to May 2015. At the interim analysis as of August 2015, 787 pts were evaluable for safety and efficacy: male 57%; age ≥ 65 yrs 52%; ECOG Performance Status (PS) 0/1/2 40%/51%/10%; KRAS status wild-type/mutant 50%/47%; treatment line of REG 3rd /4th/ ≥ 5thline 40%/36%/24%; starting dose of REG 160 mg/120mg 66%/22%. Drug related adverse events (AE) were reported in 702 pts (89%). Most common AEs were hand foot skin reaction [(HFSR) 56%], liver dysfunction (32%, including 17% hepatic laboratory abnormalities), hypertension (27%), platelet count decreased (17%) and fatigue (14%). Rates of any grade of the major AEs typically peaked the first 2 months after starting REG and were relatively stable afterwards. Median time to treatment failure (TTF) was 2.1 months [range 1.9– 2.2]; median overall survival (OS) was 7.0 months [range 6.3– 7.8]. In exploratory analyses, rates of any grade and ≥ grade 3 HFSR and liver dysfunction were higher at the starting dose of 160mg (the dose of the first day of the first cycle) than in that of 120mg or less. Pts who had HFSR had a significantly longer OS than pts who did not (hazard ratio 0.573; 95% confidential interval0.470–0.698; p < 0.0001). TTF of pts with PS 0 tended to be longer than that of pts with PS ≥ 1. Conclusions: The safety and efficacy profiles of REG in Japanese pts in clinical practice are consistent with those of Japanese pts in the CORRECT trial. The results from > 1200 pts enrolled in the PMS will be presented at the meeting. Clinical trial information: NCT01843400.
Onset of neutropenia as an indicator of treatment response in the phase 3 RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo in patients with metastatic colorectal cancer.
Authors: Ohtsu Atsushi , Yoshino Takayuki , Falcone Alfredo , Garcia-Carbonero Rocio , Argiles Guillem , Sobrero Alberto F. , Peeters Marc , Makris Lukas , Benedetti Fabio M. , Zaniboni Alberto , Shimada Yasuhiro , Yamazaki Kentaro , Komatsu Yoshito , Hochster Howard S. , Lenz Heinz-Josef , Tran Ben , Yoshida Kenichiro , Van Cutsem Eric , Mayer Robert J. ,   On Behalf of the RECOURSE Study Group
Published: March 2017

775 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine (FTD), and a thymidine phosphorylase inhibitor, tipiracil. Primary results of the RECOURSE trial demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 vs placebo (pbo) in patients (pts) with metastatic colorectal cancer refractory/intolerant to standard therapies. Neutropenia is a common TAS-102–associated adverse event and it has been hypothesized to be associated with a relatively high FTD concentration in pts. Methods: RECOURSE data were analyzed post hoc for correlations between onset of neutropenia (Grade 3/4) and survival benefit. Results: Of 533 pts given TAS-102, 75 (14%) developed Grade 3/4 neutropenia in treatment cycle 1, 86 (16%) for the first time in cycle 2, and 39 (7%) for the first time in cycle ≥3. Onset of neutropenia at any cycle was associated with longer median OS and PFS compared with no neutropenia. A consistent survival benefit was observed regardless of the cycle of initial onset of neutropenia, as demonstrated by the hazard ratio (against cycle-matched pbo control groups) and corresponding median OS differences (Table). Conclusions: An association between occurrence of earliest onset of Grade 3/4 neutropenia and survival benefit was observed. The data indicate that such survival benefit occurred regardless of whether the initial onset of neutropenia occurred after cycle 1, cycle 2, or later. Further analyses are required to fully determine whether FTD pharmacokinetics correlate with TAS-102 efficacy and onset of neutropenia, and whether cycle initiation delays affect response. Clinical trial information: NCT01607957. [Table: see text]
Time to grade ≥3 adverse events in pts receiving trifluridine/tipiracil (TAS-102).
Authors: Van Cutsem Eric , Ohtsu Atsushi , Lopez Busto Natividad , Kanehisa Akira , Fougeray Ronan , Winkler Robert , Mayer Robert J. 
Published: March 2017

788 Background: The phase 3 RECOURSE showed that treatment with trifluridine/tipiracil in patients (pts) with refractory metastatic colorectal cancer was associated with significantly improved survival versus placebo (7.1 versus 5.3 months, respectively; HR for death 0.68, 95% CI 0.58–0.81, p < 0.001), with few serious adverse events. Trifluridine/tipiracil is administered in 4-week cycles comprising 2 weeks with 5 days at 35 mg/m2 bid followed by 2 rest days, and then a 2-week rest period. Exploration of timing for AEs, particularly within the first cycle of treatment, is important for pt monitoring in the outpatient setting. Methods: We performed a post hoc analysis of the RECOURSE safety population (533 trifluridine/tipiracil; 265 placebo) to explore timing of hematological and nonhematological AEs. Results: Grade ≥ 3 adverse events (AEs) were more frequent with trifluridine/tipiracil than placebo for both hematological AEs (38% vs 0% neutropenia; 4% vs 0% febrile neutropenia; 18% vs 3% anemia; and 5% vs < 1% thrombocytopenia) and nonhematological AEs (2% vs 1% nausea; 2% vs < 1% vomiting; and 3% vs < 1% diarrhea). The median time to nadir in cycle 1 for hematological events was 28 days (17–31) for grade ≥ 3 neutropenia, 22 days (9–39) for grade ≥ 3 anemia, and 18 days (9–33) for grade ≥ 3 thrombocytopenia; similar values were obtained in subsequent cycles. The median times to nadir and values at nadir over the whole treatment duration (all cycles) are presented in the table for hematological and nonhematological AEs. Conclusions: Hematological and nonhematological AEs with trifluridine/tipiracil appear to be most intense towards the end of treatment cycles, which is reassuring for its use in the outpatient setting. Clinical trial information: NCT01607957. [Table: see text]
Response rate and survival for patients with metastatic colorectal cancer from right-sided versus left-sided tumors, treated with first-line triplet chemotherapy with bevacizumab.
Authors: Bazarbashi Shouki , Omar Ayman , Aljubran Ali Husain , Alzahrani Ahmed M 
Published: March 2017

801 Background: Recent data have shown that right sided colonic cancer represent a molecularly different class of tumors from the left sided ones with worse survival in patients treated with doublets systemic chemotherapy. We report the result of response and survival on patients treated with triplet chemotherapy according to the primary tumor location. Methods: Medical records of patients treated with triplet chemotherapy (capecitabine, oxaliplatin and irinotecan) in combination with bevacizumab on a prospective clinical trial (clinicaltrial.gov: NCT01311050), were retrospectively reviewed for the location of primary tumor. Right sided tumors: from cecum to hepatic flexure. Left sided tumors: from splenic flexure to and including the rectum. Transverse colon were excluded. Patients who had multiple primaries were considered right sided if at least one of them was right sided. Results: Fifty-three patients treated with above triplet therapy. Eleven were right sided and 42 were left sided. Characteristics for right vs left sided tumors were as follow: Median age: 46 (range 24-55 years) vs 53 ( 32-74 years), male: 5 (46%) vs 23 (55%), performance status 0-1: 9 (82%) vs 37 (88%), KRAS wild: 3 (27) vs 12 (29%), single metastatic site: 5 (46%) vs 14 (33%) and Prior adjuvant chemotherapy: none vs 6 (14%). Response rate (complete and partial) were 6 (54%) in right sided tumors and 24(57%) in left sided tumors. Progression free and overall survival for right sided tumors was 22 (95% confidence interval (CI) 12.3-31.7) and 22 months (95% CI 16.6-27.4) and for left sided tumors were 12 (95% CI 3.5-20.5) and 28 months (95% CI 22.7-33.2) respectively. Conclusions: First-line triplet chemotherapy with bevacizumab may overcome the poor prognosis of metastatic right sided colonic cancer. Clinical trial information: NCT01311050.
A phase 1b/2, open label, dose-escalation study of margetuximab (M) in combination with pembrolizumab (P) in patients with relapsed/refractory advanced HER2+ gastroesophageal (GEJ) junction or gastric (G) cancer.
Authors: Catenacci Daniel V.T. , Kim Sunnie S. , Gold Philip Jordan , Philip Philip Agop , Enzinger Peter C. , Coffie Joe , Schmidt Emmett V. , Baldwin Malcolm , Nordstrom Jeffrey L. , Bonvini Ezio , Wigginton Jon M. , Hochster Howard S. , Denlinger Crystal Shereen , Uronis Hope Elizabeth , Bendell Johanna C. , Kelly Ronan Joseph , Davidson-Moncada Jan Kenneth , Lockhart Albert C. 
Published: March 2017

TPS219 Background: Prognosis for advanced HER2+ GEJ and G cancers remains poor, with median survival just beyond one year. Trastuzumab (T) in combination with chemotherapy is the initial treatment of choice, but therapeutic options targeting HER2 beyond T are poorly defined. M is an Fc-enhanced monoclonal antibody (Mab) to HER2 that recognizes with similar affinity the same epitope as T and whose Fc domain, compared to T, binds with increased affinity to the activating CD16A Fc-receptor (FcR) and decreased affinity to the inhibitory CD32B FcR. Preliminary data shows that M monotherapy has clinical activity against HER2+ tumors in GEJ and G cancer patients previously treated with T or other anti-HER2 agents. P is a Mab that blocks the interaction of the immune checkpoint molecule, PD-1, with its ligands, facilitating tumor cell elimination by releasing tumor-associated T cells from exhaustion. Monotherapy P has demonstrated remarkable and durable clinical activity in a Phase I study. Safety profiles of M and P are acceptable and non-overlapping. Methods: This study advances a chemotherapy free combination of M + P treatment for advanced HER2+ GEJ and G cancer patients. Enrolled patients will have relapsed/refractory HER2+ GEJ or G adenocarcinoma with measurable disease that has progressed on T plus first line chemotherapy. HER2+ (IHC 3+ or ISH+) will be confirmed by central review. Two dose levels of M (10mg/kg and 15mg/kg) and a fixed dose of P (200mg) will be evaluated for safety and tolerability. Patients will receive combination treatment once every 21 days for up to 24 months, until confirmed disease progression or intolerable toxicity. Dose expansion will enroll up to 60 patients, with 20 undergoing pre- and on-treatment biopsy. Response will be assessed every 6 weeks for the first 6 months and every 12 weeks thereafter per RECIST v1.1 and immune RECIST to account for response patterns observed with immunotherapies. Primary endpoint is ORR and duration of response, and secondary endpoints include PFS and OS. The study was initiated on January 2016 and is ongoing in North America and Asia. Clinical trial information: NCT02689284.
Exploratory study of intraperitoneal paclitaxel plus mFOLFOX6 for gastric cancer patients with peritoneal metastasis and inadequate oral intake.
Authors: Yoshida Shuntaro , Ishigami Hironori , Muro Kei , Kadowaki Shigenori , Tsuji Yasushi , Ohta Yumiko , Yamashita Hiroharu , Yamaguchi Hironori , Kitayama Joji ,   Japan Intraperitoneal Chemotherapy Study Group (JIPG)
Published: March 2017

TPS222 Background: Systemic chemotherapy with oral fluoropyrimidine and platinum is recommended for the first-line treatment for unresectable or recurrent gastric cancer in Japan. However, some patients with severe peritoneal metastasis cannot take oral medications because of obstruction or dysfunction of the gastrointestinal tract. FOLFOX is regarded as one of the candidates for the standard of care for gastric cancer, and is now being evaluated in clinical trials. Intraperitoneal (IP) paclitaxel (PTX) provides sustained high local concentrations, and its efficacy has been shown in ovarian and gastric cancer. We developed a regimen combining IP PTX with S-1/PTX, and the phase III trial comparing with S-1/cisplatin suggested efficacy of this regimen. Therefore, we designed a regimen combining IP PTX with mFOLFOX6, and started an exploratory study in gastric cancer patients with peritoneal metastasis and inadequate oral intake. Methods: This is a prospective, multicenter, single-arm phase I/II study. Eligibility criteria include: pathologically proven unresectable or recurrent gastric adenocarcinoma; peritoneal metastasis; inadequate oral intake; adequate bone marrow function; acceptable liver and renal function; ECOG performance status of 0-2 and age between 20-80 years. Patients undergo diagnostic laparoscopy and are implanted with an IP port in the subcutaneous space of the lower abdomen, with a catheter placed in the pelvic cavity. mFOLFOX6 is administered bi-weekly, and IP PTX 20 mg/m2 is administered through an IP port on days 1, 8 and 15. The treatment course is repeated every 4 weeks until disease progression or unacceptable toxicity. The primary endpoint is the 1-year overall survival rate. Secondary endpoints are progression free survival, time to treatment failure, response rate, negative conversion rate on peritoneal cytology and safety. Twenty medical institutions from all over Japan participate in this study, and 34 patients are to be enrolled in two years. Toxicity will be evaluated in the early stage, and the protocol will be reconsidered and revised if all of the first 3 or more than 2 of the first 6 patients develop dose-limiting toxicities. Clinical trial information: UMIN000019206.
Phase I study of defactinib combined with pembrolizumab and gemcitabine in advanced cancer.
Authors: Wang-Gillam Andrea , Lockhart Albert C. , Tan Benjamin R. , Suresh Rama , Singh Preet Paul , Lim Kian-Huat , Pedersen Katrina , Amin Manik A. , Hawkins William G. , DeNardo David G 
Published: March 2017

TPS505 Background: Focal adhesion kinase (FAK) is consistently hyperactivated in pancreatic ductal adenocarcinoma (PDAC), and FAK signaling is a key driver in forming its fibrotic and proinflammatory tumor microenvironment. Inhibition of FAK signaling leads to significant reduction of pancreatic tumor growth in animal models. Indeed, tumors treated with FAK inhibitors displayed markedly reduced tumor fibrosis and decreased immunosuppressive myeloid cells. Furthermore, our preclinical work has demonstrated that FAK- and PD-1 inhibitors elicit significant tumor regression, and the maximal response was achieved by combining FAK- and PD-1 inhibitors with gemcitabine, suggesting the need for a cytotoxic agent to bolster antigen presentation (Jiang H et al, Nature Medicine 2016). Defactinib is an orally available, potent ATP-competitive, FAK inhibitor with a recommended phase II dose (RP2D) of 400 mg twice daily. Methods: Eligible patients will be treated according to the dose escalation schema. A 3+3 design is used until the first occurrence of dose-limiting toxicity, and then switches to a continuous assessment design. The study has an expansion portion (group A and B) at the RP2D. Group A includes metastatic PDAC patients who are stable at least 4 months on front-line nab-paclitaxel/gemcitabine, and group B includes metastatic PDAC patients progressed on ≥ 1 chemotherapy line. Key eligibility criteria include patients with advanced solid tumors (dose escalation portion) or advanced PDAC (expansion cohort); age ≥18 years; ECOG score ≤1; normal organ function; and no history autoimmunity. The primary endpoint is to determine the RP2D. Secondary endpoints include objective response rate, progression-free survival and overall survival. The exploratory endpoints include developing a molecular and immune signature for treatment response. This trial is actively enrolling and funded by Precision Medicine Research Associate and Barnes Jewish Foundation. Clinical trial information: NCT02546531. [Table: see text]
An open-label, randomized, controlled clinical trial to explore the curative effects between the treatment of capecitabine and andrographolide and the single capecitabine in the patients with pathological and/or histologic diagnosed unresectable, advanced, recurrent, and metastatic colorectal cancer.
Authors: Shu Yongqian , Sun Jing , Cai Peifen , Wang Weicheng , Han Xiao , Gu Yanhong 
Published: March 2017

TPS819 Background: Colorectal cancer (CRC) is one of the most commonly diagnosed solid tumors worldwide. Current therapies for the treatment of CRC mainly comprise fluoropyromidine-based chemotherapies that are used individually or in combination with oxaliplatin or/with target therapy. Andrographolide, a natural diterpenoid from Andrographispaniculata, has been reported to exert antibacterial, antiviral, anti-inflammation and neuroprotectiveactivities. Our previous studies have proved that Andrographolide can inhibit tumor growth in mice at a relatively high dose(about 200 mg/kg).The aim of the study is to make a comparison of PFS, RR, and OS of the elderly CRC between the treatment of xeloda and andrographolide and the signal xeloda.We look forward to these findings highlight the potential possibility of using this natural, safe and relatively inexpensivecompound as potential adjunctive treatments in improving the overall treatment response of patients with CRC in future. Methods: This is an open-label, randomized, controlled clinical trial. Patients older than or equal to 65, by pathological and/or histologic diagnosed unresectable, advanced, recurrent andmetastatic CRC, will be enrolled. These patients’ tumors must be clearly measured by radiographic technology. All cases of chemotherapy patients randomly divided into two groups, experimental group (xeloda with andrographolide): xeloda: 1250mg/m2 , po bid, d1–14, q3w; andrographolide: 500mg, ivd qd, d1–14, q3w; control group (xeloda): 1250mg/m2, po bid, d1–14, q3w, 21d/cycle. After each 2 cycles, patients will be examined by imageological tests (CT and/or MRI) or tumour biomarkers (CEA and CA199) to estimate the curative effects. Until the tumor progression or after 6 cycles, patients will be removed from this study. PFS is set as the primary endpoint while secondary endpoints include overall survival (OS), overall response rate (ORR), and health-related quality of life (HRQoL). Recruitment has begun in Jan 2014 and about 52 patients has joined this study. Clinical trial information: NCT01993472.