bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter prospective study on the efficacy and safety of denosumab in gastrointestinal cancer patients receiving short-term periodic steroid premedication for prevention of chemotherapy-induced nausea and vomiting: ESPRESSO-02/HGCSG1602.
Authors: Nakamura Michio , Yagisawa Masataka , Sawada Kentaro , Muranaka Tetsuhito , Nakatsumi Hiroshi , Kawamoto Yasuyuki , Yuki Satoshi , Dazai Masayoshi , Ishiguro Atsushi , Kobayashi Yoshimitsu , Sogabe Susumu , Miyagishima Takuto , Iwanaga Ichiro , Tateyama Miki , Hatanaka Kazuteru , Ono Kota , Sakata Yuh , Komatsu Yoshito 
Published: March 2017

TPS809 Background: We previously reported that short-term periodic premedication of glucocorticoids (GCs) used with chemotherapy for gastrointestinal cancer (GIC) caused the reduction of bone mineral densities (BMD) and the increase of serum bone alkaline phosphatase (BAP) (ESPRESSO-01 study; ASCO-GI 2016 Abst.523). Surprisingly, it seems that the BMD decreasing levels due to only the 16-week GC usage in GIC chemotherapy were comparable to that of the 12-month adjuvant aromatase inhibitor therapy for early stage breast cancer patients or the 12-month androgen deprivation therapy for nonmetastatic prostate cancer patients. So we conducted this study to evaluate the efficacy and safety of denosumab for prevention of chemotherapy-induced BMD decreasing. Methods: This is a multicenter single-arm prospective study to evaluate the efficacy and safety of denosumab in GIC patients receiving the short-term periodic steroid premedication. The key eligibility criteria are as follows: 1) Histologically confirmed adenocarcinoma in GIC, including esophageal, gastric, pancreatic, and biliary cancer. ; 2) A schedules of periodical intravenous steroid administration as premedication that was weekly, biweekly, and triweekly, and in which > 4-week steroid-free intervals were not allowed. ; 3) High risk patient with steroid induced secondary osteoporosis. ; 4) No prior treatment for osteoporosis. The dose of denosumab (Prolia) is 60mg administered as a single subcutaneous injection within a week before the induction of chemotherapy. All participants should receive adequate calcium and vitamin D supplementation. The primary endpoint is to investigate the BMD change and bone turnover markers (serum NTX and BAP levels) between baseline and 16 weeks after induction of chemotherapy. And the secondary endpoints are to compare and evaluate the difference of primary site, treatment regimen, dose intensity of steroids, newly bone fractures, and the FRAX output. This study is sponsored by Hokkaido Gastrointestinal Cancer Study Group. Clinical trial information: UMIN000023855.
Cetuximab metastatic colorectal cancer strategy (ERMES) study: A phase III randomized two arm study with FOLFIRI + cetuximab until disease progression compared to FOLFIRI + cetuximab for 8 cycles followed by cetuximab alone until disease progression in first-line treatment of patients with RAS and BRAF wild type metastatic colorectal cancer.
Authors: Pinto Carmine , Normanno Nicola , Orlandi Armando , Maiello Evaristo , Bilancia Domenico , Corsi Domenico C. , Tamburini Emiliano , Pisconti Salvatore , Ferraú Francesco , Di Costanzo Francesco , Gori Stefania , Daniele Bruno , Tonini Giuseppe , Zaniboni Alberto , Soto-parra Hector , Frassinetti Giovanni Luca , Iaffaioli Rosario Vincenz , Zampino M. Giulia , Repetto Lazzaro , Barone Carlo Antonio ,   ERMES Study Group
Published: March 2017

TPS810 Background: The optimal duration and content of first-line therapy in mCRC pts once they have achieved objective response is controversial. In the FIRE-3 trial, ETS was significantly associated with PFS and OS. Based on this evidence it can be hypothesized that once this goal has been achieved, further exposure to combined antineoplastic treatment may not result in improvement or preservation of such result but only in an increase of toxicity. We designed a strategy study to compare FOLFIRI + cetuximab until PD to FOLFIRI + cetuximab for 8 cycles followed by cetuximab alone until PD in first line treatment of RAS/BRAF WT mCRC pts. Methods: This is a multicenter, open-label, randomized phase III trial. Untreated and unresecteble RAS/BRAF WT mCRC pts were randomized 1:1 to receive Cetuximab (400 mg/mq w1 and then 250 mg/mq weekly) + FOLFIRI until PD (standard arm) or Cetuximab (400 mg/mq week 1 and then 250 mg/mq weekly) + FOLFIRI for 8 cycles followed by Cetuximab monotherapy until PD (experimental arm). Tumor assessment is planned every 8 weeks. The objective of the study is to demonstrate a not inferior efficacy and a better toxicity profile for the experimental treatment compared to the standard treatment. The co-primary endpoints are PFS and incidence of G 3-4 AEs. Secondary endpoints are OS, ORR, ETS (8 weeks) and safety. A prospective multiple gene mutation analysis by NGS of both tumor tissue and blood will be performed to find potential predictive factors and surrogate markers of treatment efficacy. The two co-primary endpoints will be compared between the two arms using a fixed-sequence testing procedure to control for the family-wise type I error rate of 0.05 in a strong sense. This sequence considers that a reduction of grade 3-4 AEs is only of relevance, if non-inferiority is shown regarding PFS. 600 evaluable pts will be enrolled and randomized. Study recruitment started on January 2015, currently 139 pts have been randomized. Clinical trial information: NCT02484833.
ISO-005; An open-label, multiple-site, dose cohort, phase I/II study in patients with stage IV colorectal cancer.
Authors: Taflin Helena Anna , Wettergren Yvonne , Odin Elisabeth , Haux Johan , Gustavsson Bengt , Carlsson Goran Ulf 
Published: March 2017

TPS811 Background: Chemotherapy treatment of Colorectal Cancer, usually includes combinations with 5-Fluorouracil (5-FU). 5-FU is always combined with Leucovorin, (LV), which significantly enhances the therapeutic effect of 5-FU. The principal mechanisms of action are the same for Modufolin as for LV. However, in contrast to LV, Modufolin does not require metabolic activation to exert its effects - a clear advantage since the activation capacity shows great intra- and inter-individual variability leading to insufficient and unpredictable responses to LV in some patients. Methods: ISO-CC-005 is a multiple-site, international phase I/II study in patients with Stage IV Colorectal Cancer eligible for 5- FU/LV therapy alone or in combination with oxaliplatin or irinotecan. The study will investigate the tolerability of Modufolin at four dose levels and is designed as a safety study. Tolerability will be assessed by analysing the number and severity of DLTs associated with the chemotherapeutic agents, adversed events and the number of dose adjustments observed for each of the chemotherapeutic agents used in the different treatment arms. 39 valid patients are planned for inclusion, who will receive Modufolin twice every two weeks during four chemotherapy cycles. The study is on-going and still recruting eligible patients. Clinical trial information: NCT02244632.
Phase 1 study of infusional or bolus deflexifol (a novel formulation of 5FU, folinic acid, and cyclodextrin) after failure of standard treatment.
Authors: Clingan Philip R. , Ackland Stephen P. , Ranson Marie , De Souza Paul , Tafreshi Ali , Aghmesheh Morteza , Brungs Daniel , Garg Madhu Bala , Parker Suzanne , Jokela Rebecca 
Published: March 2017

TPS812 Background: 5FU is a commonly used anti-cancer agent first synthesized in 1957, and is now most commonly used in combination with FA, which enhances its clinical activity. Physical incompatibilities between 5FU and LV necessitate the infusion of each component separately, often through a central line due to high pH; resulting in adverse events, which leads to poor outcomes due to treatment interruption and discontinuation. A novel all in one reformulation of 5FU/LV at physiological pH has been developed as an alternative to serial administration of 5FU and LV in a high Ph solution [Locke JM, Anticancer Drugs 2009]. Preclinical testing demonstrated that the reformulation is stable bioequivalent to 5FU with reduced side effects [Stutchbury TK, Anticancer drugs 2011]. Methods: An open label phase 1 dose escalation study is underway in 2 schedules (bolus and infusion) to assess the safety and tolerability in patients with advanced malignancy after failure of standard treatment (including fluoropyrimidine regimens). To determine the maximum tolerated dose defined as: 2 out of 6 patients experience DLTs dose escalation is halted and declared DLT Dose. The previous dose level will be considered for expansion to x6 patients to confirm Maximum Tolerated Dose (MTD). Also to determine pharmacokinetic profile. Patients enrolled in Cohorts 1 to 4, have been completed without DLT. Dose-limiting toxicity (DLT) is defined as: Any Grade 3 or 4 non-haematologic toxicity (CTACE criteria). Patients developing Grade 3 or 4 diarrhoea, failing maximal anti-diarrheal medications. Febrile neutropenia, Grade 4 neutropenia > 7 days, Grade 4 thrombocytopenia > 7 days Any grade of thrombocytopenia associated with bleeding. Currently proceeding with (bolus 575mg/m2 weekly x 6, infusion 3600mg/m2/46h q2W). Limited sampling PK of 5-FU and dihydoFU is being conducted (3 at each of the 5 dose levels, doses 1 and 6). In both schedules to assess PK variability, adequacy of dosing in comparison to previous reports. The incidence of AEs and SAEs (CTACE 4.03) will be summarized by severity and relationship to study treatment. Clinical trial information: 044867.
Consolidation chemotherapy for locally advanced mid- or low rectal cancer after neoadjuvant concurrent chemoradiotherapy: A multicenter, randomized controlled trial (KONCLUDE).
Authors: Kim Chang Woo , Kim Ik Yong , Lee Suk-Hwan 
Published: March 2017

TPS813 Background: Chemoradiotherapy (CRT) followed by total mesorectal excision (TME) has been a standard treatment option for locally advanced mid or low rectal cancer with improved local control. However, systemic recurrence after the standard therapy is the most important failure of treatment, and several efforts have been trying to overcome it. Consolidation chemotherapy is adding several cycles of chemotherapy between neoadjuvant CRT and TME. It could increase the proportion of pathologic complete response (pCR), subsequently could show better oncologic outcomes. Methods: Patients with advanced mid or low rectal cancer who received neoadjuvant CRT will be included after screening. They will be randomized and assigned to underwent TME followed by adjuvant chemotherapy of 8 cycles (control arm) or receive 3 cycles of chemotherapy before TME, and receive 5 cycles of chemotherapy (experimental arm). The primary endpoints are pathologic complete response and 3-year disease-free survival, and the secondary endpoints are radiotherapy-related complications, R0 resection, tumor response rate, surgery-related morbidity, and peripheral neuropathy 3 year after the surgery. The authors hypothesize that the experimental arm would show a 15% improvement in two primary endpoints, compared with the control arm. Based on the superiority design, an one-sided log-rank test with α-error of 0.025 and a power of 90% was conducted. Allowing for a drop-out rate of 10%, 316 patients (158 per arm) will need to be recruited. The accrual period is 2 years and the follow-up period is 3 years. Discussion: KONCLUDE (A Korean society of coloproctology trial: cONsolidation Chemotherapy for Locally advanced mid or low rectal cancer after neoadjUvant concurrent chemoraDiothErapy: A multicenter, randomized controlled trial) is expected to provide evidence to support clear treatment guidelines for patients with locally advanced rectal cancer. Clinical trial information: 02843191.
Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single arm phase II study (FOTAC).
Authors: Zhang Jianwei , Cai Yue , Hu Huabin , Xiao Jian , Chen Dianke , Ling Jiayu , Huang Meijin , Wang Lei , Kang Liang , Lan Ping , Wang Jianping , Deng Yanhong 
Published: March 2017

TPS816 Background: Preoperative 5-Fluorouracil based chemoradiotherapy is the standard of treatment for locally advanced rectal cancer. About 15% to 18% of patients would achieve pathologic complete response (pCR) after 5-Fluorouracil based chemoradiation. And the survival outcome of patients with pCR was much better than that of non-pCR. In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that totally neoadjuvant chemoradiation therapy with mFOLFOX6 could improve the pCR rate from 18% to 45% with 5% type I error and 80% power. Fifty patients met inclusion criteria will be enrolled in the trial. All patients will receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before operation. Totally, the patients will receive 8-10 cycles of chemotherapy before surgery. MRI of the pelvic will be performed every 4 cycles of the therapy to assess clinical response. Then the patient will receive total mesorectal excision at least 8 weeks after radiotherapy. The post-operative chemotherapy will be omitted and all the patients go to surveillance. Clinical trial information: NCT02887313.
Steroid-free regimen with aprepitant in preventing chemotherapy-induced nausea and vomiting in patients with colorectal cancer receiving FOLFOX chemotherapy: A randomized phase III trial.
Authors: Wang Wenjing , Ling Jiayu , Cai Yue , Zhang Jianwei , Hu Huabin , Li Shanshan , Xiao Jian , Deng Yanhong 
Published: March 2017

TPS820 Background: Addition of aprepitant, an NK1 receptor antagonist to a 5-HT3 receptor antagonist and dexamethasone regimen was shown to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC). Little is known about the efficacy of aprepitant when used without dexamethasone. Dexamethasone is widely used to prevent both acute and delayed nausea and vomiting induced by chemotherapy. However, multi-period use of dexamethasone could be associated with side effect, such as hyperglycemia, dyspepsia and insomnia. This randomized phase III trial studies antiemetic therapy with aprepitant and tropisetron to see how well they work compared to dexamethasone plus tropisetron in preventing chemotherapy-induced nausea and vomiting in patients with colorectal cancer receiving FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) chemotherapy. Methods: This trial is an open-label, single-center, randomized phase 2 study. Eligibility criteria include histologically confirmed colorectal cancer, no prior chemotherapy and scheduled to receive FOLFOX, Age ≥ 18 years, ECOG Performance Status 0, 1 or 2. Up to 298 patient will be enrolled and randomized 1:1 to receive aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 and 3) plus tropisetron (5mg IV of day1) or dexamethasone (10 mg IV on day 1 and 5 mg IV on days 2, 3) plus Tropisetron (5mg IV of day1). The primary objective of this study is complete response defined as no emetic episodes and no use of rescue medication. The second objectives include nausea score, time to first vomiting episode or use of rescue medication, frequency of rescue medication and functional Living Index -Emesis (FLIE). Clinical trial information: NCT02909478.
Barriers to care in two differing models of follow-up for long-term childhood cancer survivors.
Authors: Russell Brooke , Reynolds Kathleen , Spavor Maria , Giese-Davis Janine 
Published: March 2017

100 Background: Long-term childhood cancer survivors (CCSs) require lifetime medical follow-up to screen for and treat adverse health outcomes related to cancer and its treatment. In Alberta, primary-care providers (PCPs) are involved in this follow-up care, though differently so in Northern and Southern regions of the province. Our aim was to identify potential province-wide and region-specific preferences and care barriers that may impact medical and quality-of-life outcomes for patients. Methods: Forty-four PCPs following CCSs completed surveys about knowledge gaps, communication, and health-system barriers. Knowledge gaps were assessed using a hypothetical case vignette followed by three multiple-choice questions regarding appropriate follow-up, based on available guidelines. Communication barriers were measured using a 6-item 5-point scale. Health-system barriers were measured using a 12-item 5-point scale. Results: PCPs were 54.54% female, age 31-72 ( m=51.36) with 1-50 years of practice ( m=22.49). These preliminary results suggest PCPs across Alberta are experiencing moderate communication barriers (scale: 0-24, m=10.85, SD=6.59) but fewer health-system barriers (scale: 0-48, m=14.58, SD=5.11). Scores on the case vignette were markedly low province-wide (scale: 0-3, m=0.65, SD=0.65), indicating considerable knowledge gaps regarding long-term oncology-related care follow-up. No statistically significant differences were observed between regions. Conclusions: Albertan PCPs are experiencing barriers to care and knowledge gaps when following ASCCs. This is of primary concern for PCPs in Southern Alberta, currently tasked with the sole responsibility of providing oncology-related follow-up care. These data will be linked with data collected from their patients to explore the relationship between PCPs’ barriers and knowledge, and the symptoms, quality of life, and unmet needs of their patients.
Understanding and improving knowledge of cancer survivorship care among college providers.
Authors: Psihogios Alexandra M , Schwartz Lisa , Pauly-Hubbard Helen , Ginsberg Jill P. , Hobbie Wendy , Szalda Dava 
Published: March 2017

101 Background: Young adult survivor (YAS) engagement in follow-up care is often compromised by competing developmental transitions, including attending college away from home and pediatric oncology team, as well as community providers’ deficits in knowledge related to caring for YAS. The aims were to assess college providers’ basic knowledge of the risks of YAS and related care guidelines and determine whether an educational in-service is an effective platform for increasing college health providers’ knowledge about survivorship. Methods: During Phase 1, 40 college health and office of disability staff members from public and private colleges/universities (90.0% female) completed a 41-question survey on their experiences with students who were YAS. In Phase 2, a one-hour educational in-service was provided to 18 health center medical providers (94.1% female) at a private university. In-service content was informed by the original survey. Providers completed pre- and post-test assessments of knowledge about late effects, knowledge of resources, and comfort with caring for YAS. Results: While most providers indicated that YAS are at risk of chronic health conditions because of their cancer treatment (70.6%), nearly all were unfamiliar with the published long-term follow-up guidelines for cancer survivorship (93.8%). Over half of providers did not have knowledge of cancer survivorship services in their area (58.8%). All respondents were interested in more survivorship education. Attendees of the in-service had higher knowledge of survivorship follow-up guidelines at the post-test assessment ( M=4.19) compared to the pre-test ( M=1.81), t=-5.56, p < .001. They endorsed higher awareness of local resources at post-test ( M = 3.67) compared to the pre-test ( M=2.13), t=-3.62, p < .01. Attendees reported higher comfort with caring for cancer survivors at post-test ( M=3.00) compared to the pre-test ( M=2.00), t=-3.42, p< .01. Conclusions: College providers had little baseline knowledge of cancer survivorship guidelines, but were motivated to obtain more information. An in-service improved college health providers’ knowledge of caring for YAS, awareness of published guidelines, and comfort in providing care.
Risk of coronary heart disease and ischemic stroke in thyroid cancer patients taking levothyroxine.
Authors: Shin Dong Wook , Suh Beomseok , Yoon Jae Moon , Park Youngmin 
Published: March 2017

105 Background: Many thyroid cancer patients are exposed to long-term TSH suppression, in many cases as lifetime treatment, and are consequently subjected to risk for cardiovascular disease. We investigated incidence of CHD and ischemic stroke among thyroid cancer patients and explored possible pathophysiological mechanisms involved. Methods: A total of 182,419 subjects who received thyroidectomy for thyroid cancer during 2004-2012 were selected from the Korean National Health Insurance data, which covers approximately 97% of the entire Korean population. Propensity score matching was used to select non-cancer controls. Cox proportional hazards regression analysis was used to determine relative risk of coronary heart disease (CHD), and ischemic stroke. Mean follow-up was 4.32 years. Results: Thyroid cancer patients had elevated risk for CHD and ischemic stroke with HR 1.15 (95% CI 1.10-1.22), and 1.15 (1.09-1.22), respectively. This risk was marked in those who received total thyroidectomy and in those who took higher dosage of levothyroxine (HR 1.47, 95% CI 1.34-1.60 for CHD and HR 1.56, 95% CI 1.42-1.72 for ischemic stroke among those who took ≥ 170mcg/d). Atrial fibrillation risk was dose-dependently associated with levothyroxine dosage; however, once patients developed atrial fibrillation, ischemic stroke risk was not significantly greater in those who took higher dosage. Conclusions: The risk for CHD and ischemic stroke was higher in thyroid cancer patients who received thyroidectomy, and the dosage of levothyroxine administered appears to play a major role. More caution is suggested for the choice of thyroidectomy and TSH suppression therapy, as well as proper management for cardiovascular disease prevention.