bluuebunny/crossref_metadata_2025_split huggingface dataset:
Panitumumab (pmab) in patients (pts) with chemorefractory metastatic colorectal cancer (mCRC): Final analysis from a community-based, observational study (VECTOR) in Germany.
Authors: Lerchenmuller Christian A. , Groschek Matthias , Kroening Hendrik , Scheuer Burkhard , Stauch Martina , Kuhn Anja , Hellebrand Eva , Vehling-Kaiser Ursula 
Published: February 2017

550 Background: Pmab monotherapy significantly improves progression-free survival versus best supportive care in pts with chemorefractory KRAS wild-type (WT) mCRC. This study evaluated the efficacy and safety of pmab in routine clinical practice in Germany. Methods: To ensure a representative sample, eligibility criteria were largely unrestricted. Consenting pts were >18 years old, had histologically confirmed KRAS WT mCRC, >4 weeks pmab therapy, failure of fluoropyrimidine-, oxaliplatin- and irinotecan-containing chemotherapy (CTx) regimens, and women of child-bearing age received contraception. Predefined endpoints were overall response rate (ORR; investigator`s assessment) and skin toxicity (NCI Common Terminology Criteria for Adverse Events v3.0). Results: A total of 428 pts were included in the full analysis set. At the start of pmab therapy, median age was 69 (range 22-89) years, 268 pts (63%) were male and 343 (80%) had an ECOG performance status of 0-1. Overall, 400 pts (93%) had undergone prior surgery and 154 (36%) had received ≥1 cycle of adjuvant CTx. Pts had received a median of 3 cycles (range: 1‑12) of prior CTx for mCRC. The most common regimens were FOLFOX/FOLFIRI ±antibody therapy; 65% of regimens were given with palliative, 32% with curative/palliative and 3% with curative intent. The median pmab dose was 6 mg/kg (range 2.4-7.2) q2w for a median of 8 (range 2‑45) cycles, with 143 pts (33%) receiving >10 cycles. The ORR during pmab therapy was 20% (complete response: n=7 [2%]; partial response: n=77 [18%]); disease control (including stable disease) was achieved in 261 pts (61%). Skin reactions occurred in 324 pts (67%) with 52% experiencing a maximum grade ≥2. Most pts had some type of rash (48% acne, 5% desquamation, 4% hand-foot skin reaction, 1% erythema multiforme). Overall, 21% of pts had other toxicities. Three serious adverse drug reactions (infection/fever; thrombosis/embolism; erythema multiforme) and two grade 1 infusion reactions were reported. Conclusions: In this observational study, pmab monotherapy had efficacy at least as good as was seen in the randomised pmab trial and safety was also similar.
The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: CCOG 0902 study.
Authors: Watanabe Takuya , Nakayama Goro , Ishigure Kiyoshi , Hayashi Naomi , Yaguchi Toyohisa , Kojima Hiroshi , Tsuboi Kenji , Ito Akihiro , Deguchi Tomohiro , Sekiya Masanori , Tanaka Chie , Ando Yuichi , Ohashi Norifumi , Kodera Yasuhiro ,   Chubu Clinical Oncology Group
Published: February 2017

564 Background: XELOX plus bevacizumab (BEV) is an established first-line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first-line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty one patients (59%) were reintroducted oxaliplatin. The response rates and disease control rates were 57% and 96% in the initial XELOX plus BEV, 6.1% and 73% in Cape plus BEV maintenance therapy. Median PFS in initial XELOX plus BEV was 11.0 months (95%CI: 7.8-14.1). One year survival rate was 86%. Conclusions: XELOX plus BEV was feasible as a first line treatment with mCRC. The most cases achieved disease control during Cape plus BEV maintenance therapy. Clinical trial information: UMIN000006478.
Neoadjuvant capecitabine and oxaliplatin (XELOX) with bevacizumab for locally advanced rectal cancer.
Authors: Hasegawa Junichi , Mizushima Tsunekazu , Kim Ho Min , Miyake Yasuhiro , Takemoto Hiroyoshi , Tamagawa Hiroshi , Noura Shingo , Ohue Masayuki , Fujii Makoto , Fujie Yuichiro , Ota Hirofumi , Kato Takeshi , Fukunaga Mutsumi , Takemasa Ichiro , Ikeda Masataka , Yamamoto Hirofumi , Sekimoto Mistugu , Nezu Riichiro , Doki Yuichiro , Mori Masaki ,   Multicenter Clinical Study Group of Osaka University, Colorectal Cancer Treatment Group
Published: February 2017

566 Background: Chemoradiotherapy (CRT) followed by surgery is a standard treatment for locally advanced rectal cancer. Although preoperative CRT decreases local recurrence (LR), pelvic radiation is associated with long-term morbidity. We conducted this study to evaluate the feasibility of neoadjuvant XELOX with bevacizumab (Bmab) in patients (pts) with locally advanced rectal cancer. Methods: Pts with T4 or lymph node (LN) positive rectal cancer were treated with 3 cycles of XELOX with Bmab and one additional cycle of XELOX. Total mesorectal excision was performed 3-8 weeks after the last chemotherapy. The primary endpoint was to assess feasibility and secondary endpoints were R0 resection rate, down staging rate, pathological complete response (pCR) rate and pathological effect over grade 2 (tumor cell death in more than two-thirds of the entire lesion). Results: Twenty five pts were recruited between December 2009 and November 2011. Characteristics of pts were as the following: male/female, 18/7; median age, 63 years (range, 37-75); median diameter of tumor, 52.8mm (range, 38.3-110); T2-T3/T4a/T4b, 7/8/10 and N0/N1/N2, 3/14/8. In 4% of the pts (7 pts), following grade 3-4 adverse events occurred; neutropenia, hypertension, bleeding, rectal obstruction, pelvic infection, anorexia and nausea. The down staging rate of T2-T3/T4a/T4b and N1/N2 were 29/63/50 % and 86/63 %, respectively. Seven pts (28%) discontinued the treatment after 2-3 cycles of XELOX with Bmab (13% in T2-T4a, 50% in T4b). The rate of conducting surgery was 92% and all of them had R0 resections. Postoperative complications were found in 9 pts (39%). The pCR rate was 4%, and the rate of pathological effect over grade 2 was 61%. Two LR (LN positive) and two distant recurrences (1 lung, 1 liver) were reported. Conclusions: XELOX with Bmab followed by surgery was safely performed for locally advanced rectal cancer. The down staging rate was 50% even in T4b pts although half of T4b pts discontinued the study treatment. Based on these preliminary results, we are planning a phase II trial of perioperative XELOX and surgery in locally advanced rectal cancer. Clinical trial information: 000003219.
Phase I study of ursodeoxycholic acid in combination with 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab for metastatic colorectal cancer.
Authors: Lai Lily L. , Chiu Ken , Lim Dean , Chao Joseph , Frankel Paul Henry 
Published: February 2017

569 Background: Emerging data links cancer growth with aberrant metabolism. These findings suggest that treatment directed against CRC metabolism may improve survival outcomes. Bile acids are involved in the metabolism of cholesterol and glucose. The bile acid, ursodeoxycholic acid (UDCA), protects against intestinal polyp development in animal and human studies. UDCA effects may be mediated through the nuclear receptor, farnesoid X receptor (FXR), since bile acids are the receptor’s endogenous ligands. FXR is a tumor suppressor in mouse models and a prognostic biomarker in patients with CRC. Bile acid activation of FXR in mouse models suppresses intestinal tumorigenesis. We sought to determine dose and safety of UDCA when added to standard therapy for mCRC. Methods: Patients with mCRC were accrued to an institutionally approved Phase I study. At the end of a 7-day run-in period of oral UDCA, standard doses of 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab were added. UDCA doses were escalated using a 3+3 design to determine MTD. The use of a run-in period allowed for correlative studies to identify serum biomarkers of FXR activation. Results: 11 patients were treated on three dose levels (250, 500, and 750 mg/day in divided doses). Patients were treated on protocol for a median time of 6 months with a median follow-up of 15 months. Patients were taken off protocol for progression of disease (n = 7); for declining performance status (n = 1); for toxicity (n=1); for patient refusal (n= 1). One patient remains on protocol at this time. No Grade 4 or higher toxicity was identified. Grade 3 toxicities were recorded in 5 patients; the majority was hematologic. Oral glucose tolerance tests, serum glucose and insulin levels, and serum FGF-19 were determined before and after UDCA treatment. Conclusions: UDCA, given with standard chemotherapy and biologic treatment, is safe and well tolerated in patients with mCRC. Further studies are needed to determine the efficacy of targeting FXR and cancer metabolism in mCRC. Supported by a grant from The Phase One Foundation. Clinical trial information: NCT00873275.
Patient evaluation of community nurse-led follow-up clinics for colon cancer.
Authors: Samuel Leslie M. , West Bernice ,   Aberdeenshire Community Cancer Clinics Steering Group
Published: February 2017

587 Background: Health services face an ever increasing demand for quality patient focussed healthcare with limited financial resources. Our group has designed and implemented, using non-specialist community nurses, a nurse led follow up service for patients with potentially cured colon and prostate cancers in 4 community hospitals in North East Scotland. Nurses use a structured questionnaire, take tumour specific blood tests & order some imaging. Results communicated to patients via letter from oncologist. Methods: A user-group & professionals were consulted and a customised questionnaire designed. Topic sections were-basic demographic data; mode of transport; perceptions of parking; travel; continuity of care; timing of appointments; satisfaction with service attributes; any concerns; suggestions for improvement and an overall rating score. Details of the evaluation were considered by the ethics committee as 'service evaluation'. Results: The questionnaire was successfully piloted in 5 patients. The main study targetted 100 patients, & data-collection ran from August 2010 until July 2011, the 4th year of the service. 103 questionnaires returned, all useable, from 216 sent out across 4 community clinic sites. The 48% return rate was consistent across all sites. The findings were grouped together rather than presented by clinic, due to lack of response variation by site. Verbatim comments were recorded. Returns from colon cancer patients were 75% of the total (47% M, 28% F) & 25% prostate patients. Median age 71, range 41 - 90 years. Travel was by car 87%, foot 8% & public transport 5%. Topics covered included, own health 96%, appt times 79%, tests & results 75%, patient support 37%, carer support 12% & 'other' 16%. Ranking of statements suggests 90% satisfaction with administration & 94% quality of clinic, and 85% prefer local proximity of clinic. Only 36% accompanied to clinic, less than when at central clinic. Only 8% expressed concerns, usually about scan results. Conclusions: an overwhelmingly positive patient evaluation provides evidence that non-specialist community nurses can deliver a follow up service in the community for potentially cured colon (& prostate) cancer patients.
Sentinel lymph node (SLN) mapping (M) in colon cancer (CCa) by da Vinci robotic system (DRS): First pilot study.
Authors: Saha Sukamal , Korant Alpesh , Abadeer Benjamin , Gomez-Seoane Andrew , Shaik Mohammed , Krishnamoorthy Madhumitha , Kaushal Sunil , Ganatra B. K. , Wiese David 
Published: February 2017

589 Background: SLNM in CCa has been established as an aid to the pathologist to identify the nodes most likely to harbor micrometastasis. The technique has been well- established by in vivo and ex vivo technique. No such technique has been described by DRS in CCa. Hence, a pilot study was undertaken to identify if SLNM can be performed by DRS during robotically assisted colectomy as in open cases. Methods: Patients (Pts) with CCa were randomly selected for either robotic or open surgery. During each case, 1% methylene blue dye was injected in vivo subserosally around the tumor. Standard oncologic operations were done in each case. The first 1-4 blue nodes near the tumor were tagged with suture as SLNs. Data was collected for demographics, tumor pathology and peri-operative events. Results: There were a total of 11 consecutive robotic pts and 15 open pts. The data was compared between the robotic vs open groups as follows: Primary sites including Cecum (1 vs 3), Ascending Colon (3 vs 4), Transverse Colon (4 vs 5), Sigmoid Colon (2 vs 3); Average number of LNs (18.5 vs 17.6); Average number of SLNs (3.3 vs 3.0), and nodal positivity (50% vs 50%). The success rate was 100% in each group. Conclusions: There are great similarities for SLNM between robotic and open surgeries for CCa in regards to success rate, nodal harvest, SLNs, and nodal positivity. Hence, SLNM should be pursued when robotic surgeries are performed for CCa pts as in open cases. [Table: see text]
Retrospective cohort study on the safety and efficacy of panitumumab (Pmab) for patients with metastatic colorectal cancer (mCRC): The HGCSG1002 study—Analysis of clinical early predictor for the efficacy.
Authors: Sogabe Susumu , Fukushima Hiraku , Yuki Satoshi , Kobayashi Yoshimitsu , Miyagishima Takuto , Okuda Hiroyuki , Kusumi Takaya , Doi Ayako , Tsuji Yasushi , Kawamoto Yasuyuki , Ehira Nobuyuki , Koike Masahiko , Meguro Takashi , Takahashi Yasuo , Yoshizaki Koji , Muto Shuichi , Ishiguro Atsushi , Kato Sosuke , Sakata Yuh , Komatsu Yoshito ,   Hokkaido Gastrointestinal Cancer Study Group
Published: February 2017

593 Background: Inhibition of the EGFR pathway has become a key part in the treatment of colorectal cancer. There were few studies for clinical early predictive markers. To investigate the early magnesium (Mg2+), calcium (Ca2+), albumin (Alb), CEA and CA 19-9 plasma level reductions as a predictor for clinical outcome in terms of progression free survival (PFS) and overall survival (OS). Methods: 200 patients (pts) with mCRC treated by Pmab contained chemotherapy were retrospectively registered from 20 centers in Japan (HGCSG 1002 study). Of these, the pts that were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin, and were never administered anti-EGFR-antibody, were included in this analysis. Mg2+, Ca2+, Alb, CEA and CA19-9 plasma levels were obtained from medical records. The differences in terms of PFS and OS according to the presence of Mg2+, Ca2+, Alb, CEA and CA19-9 reductions were evaluated by the log-rank test. Results: Of 67 pts were able to evaluate for this analysis. Pts’ characteristics were as follows: male/female 38/29, median age 64 (range 45-81), ECOG PS (0/1/2- ) 45/17/5. Response rate and disease control rate were 16.4% and 65.7%, PFS and OS were 4.3 m and 12.4 m, respectively. There were no correlations between Ca/Alb plasma level reductions and PFS/OS. Mg2+ reduction of at least 50% respect to the basal value during the course of treatment was significantly correlated with improved OS and PFS (OS, P=0.03; PFS, P=0.01), but the early reduction (until the 4th week or the 8th week after start of chemotherapy) was not correlated with OS and PFS. An early CEA serum level reduction of at least 40% until the 8th week was significantly correlated with improved OS and PFS (OS, P=0.04; PFS, P=0.07), moreover of at least 30% until the 4th week was correlated to longer PFS (P=0.053). Similar results were seen in CA19-9. Conclusions: An early CEA plasma level reduction of at least 30% or 40% was suggested to be a predictor for PFS in Pmab containing chemotherapy for mCRC pts. Although Mg2+ serum level reduction was correlated to clinical outcome, but could not show that is an early predictor for PFS and OS in our study.
A randomized phase II study of vismodegib (V), a hedgehog (HH) pathway inhibitor, combined with FOLFOX in patients (pts) with advanced gastric and gastroesophageal junction (GEJ) carcinoma: A New York Cancer Consortium led study.
Authors: Cohen Deirdre Jill , Christos Paul J. , Sparano Joseph A. , Kindler Hedy Lee , Catenacci Daniel Virgil Thomas , Bekaii-Saab Tanios B. , Tahiri Sanaa , Janjigian Yelena Yuriy , Gibson Michael K. , Chan Emily , Rajdev Lakshmi , Urba Susan , Wade James Lloyd , Kozuch Peter , Love Erica , Vandris Katherine , Takebe Naoko , Hochster Howard S. ,   New York Cancer Consortium
Published: February 2017

67 Background: The HH pathway is overexpressed in gastroesophageal (GE) tumors. Pre-clinically, HH inhibitors have demonstrated a reduction in GE tumor growth, cell motility and invasiveness. V, an oral small-molecule antagonist of the Hh pathway, has previously been safely combined with FOLFOX chemotherapy. Methods: Pts with untreated, metastatic or locally advanced gastric or GEJ adenocarcinoma were randomized 1:1, stratified by institution and disease status (with or w/o distant mets) to FOLFOX (ox 85 mg/m2, LV 200 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2400 mg/ m2 over 48 hrs) q14d plus V or placebo (P) (150mg PO daily). Cycle defined as 2 weeks and no crossover allowed at progression. FFPET and blood were collected for biomarker analyses. Response assessed every 8 weeks (RECIST 1.1). Primary endpoint was progression-free survival (PFS), secondary objectives were overall survival (OS), response rate (RR), and toxicity. Results: 124 pts (V/P 60/64) enrolled at 20 sites between 10/09-2/12. Pt characteristics (V/P): median age 58/62; ECOG PS 0: 23 (40%) / 30 (47%); male 39 (65%) / 53 (83%); GEJ 37 (62%) / 39 (61%); diffuse histology 20 (43%) / 14 (30%). Median number of FOLFOX cycles 9.5/11. Most common Gr ≥3 toxicities: (% pts V/P) neutropenia 50.0/31.7 (p=0.07), neuropathy 23.1/14.3 (p=0.33), fatigue 15.4/9.5 (p=0.50), thrombosis 13.5/11.1 (p=0.92), anemia 9.6/9.5 (p=0.99), hypokalemia 9.6/4.8 (p=0.52), nausea 7.7/9.5 (p=0.99). Death on or within 30 days of treatment 6.7%/15.6% (p=0.20). Median PFS in ITT population 11.5/9.3 mo (95% CI 8.5-14.4/6.7-11.9; p=0.34) and median OS 12.2/13.9 mo (95% CI 10.2-14.3/11.5-16.3; p=0.48). Non-statistically significant trends toward improved PFS with V were noted in female pts, diffuse histology, and PS 1 (p≤ 0.08). RR (%) 33/27 (p=0.64). Conclusions: Addition of V to FOLFOX did not improve PFS in an unselected advanced GE carcinoma population. Blood and tissue biomarker analyses are ongoing to determine if there is a subset of patients who may derive benefit from V. Supported by: N01-CM-62204, -62201, -62207, -62206, -62209, -62208 and 2UL1 TR000457-06 Clinical trial information: NCT00982592.
A phase ll study of trastuzumab in combination with triweekly S-1 plus CDDP in HER2-positive advanced gastric cancer (HERBIS-1).
Authors: Sugimoto Naotoshi , Tanaka Junji , Tsuda Masahiro , Okamoto Wataru , Okuda Hiroyuki , Imamura Hiroshi , Shimokawa Toshio , Sakai Daisuke , Kurokawa Yukinori , Komatsu Yoshito , Ishioka Chikashi , Tsujinaka Toshimasa , Takiuchi Hiroya , Furukawa Hiroshi 
Published: February 2017

70 Background: S-1, an oral fluoropyrimidine, plus cisplatin (SP) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer (AGC). Although ToGA study demonstrated that trastuzumab (T-mab) in combination with capecitabine plus cisplatin or fluorouracil plus cisplatin improved the overall survival of patients (pts) with HER2-positive AGC, there was no study evaluating the efficacy and the safety of T-mab in combination with SP regimen. Methods: Eligibility criteria included gastric or esophagogastric junction adenocarcinoma; HER2-positive confirmed by IHC and/or FISH (IHC 3+ or IHC 2+ and FISH positive); unresectable or recurrent; measurable lesion; no history of chemotherapy or radiotherapy; age≤75; ECOG PS of 0-1; and adequate organ function. Pts received S-1 at 40–60 mg depending on body surface area, po bid, day 1-14, and cisplatin 60 mg/m2, iv, day 1, plus T-mab 8 mg/ kg, iv, day 1 (6 mg/ kg, iv, d1 from 2nd course), repeated every 3 weeks until disease progression. Primary endpoint was response rate assessed by the RECIST (ver 1.1). The planned sample size was 50 based on the threshold response rate of 35%, the expected rate of 50%, power of 80%, and 1-sided α of 0.1. Results: A total of 56 pts were enrolled from July 2011 to May 2012. Two pts were ineligible with inadequate renal function and no measurable lesion. Characteristics of 54 eligible pts were as follows: median age of 66 (range 34-75), M/F: 42/12, PS0/1: 42/12, unresectable/recuurent: 51/3, and IHC 2+/3+: 9/45. As one patient did not receive the protocol treatment due to the rapid progression of tumor, the efficacy and the safety analyses were conducted in the full analysis set of 53 pts. The confirmed response rate assessed by the independent review committee was 68%, and the disease control rate was 94%. The response rate without interval confirmation was 75%. The grade 3/4 adverse events (>5% of pts) were as follows: neutropenia 30%, leucopenia 8%, anorexia 21%, diarrhea 8%, hypoalbuminemia 8%, vomiting 6%, and increased creatinine 6%. Conclusions: T-mab in combination with triweekly SP regimen showed promising antitumor activity and manageable toxicities in pts with HER2-positiveAGC. Clinical trial information: UMIN000005739.