bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and PK results from a phase Ib study of AL3818 (anlotinib) hydrochloride in subjects with ovarian, cervical, and endometrial cancers.
Authors: Werner Theresa Louise , Kannapel Esther , Chen Judy , Chen Melissa , Cohen Adam Louis 
Published: September 2018

e17071 Background: AL3818 (anlotinib) hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor with potential FGFR inhibition and anti-angiogenesis activity in gynecological cancers. A phase Ib dose verification study was conducted at a single U.S. center to evaluate the safety and tolerability of AL3818 and pharmacokinetic (PK) properties after oral administration of a single dose and at steady state after continuous dosing. The 12 mg dose has been used in multiple clinical trials in China for various indications including NSCLC and sarcoma. Methods: Patients with recurrent or persistent ovarian, cervical, endometrial or other uterine cancers refractory to standard therapies were eligible for enrollment in a 3+3 dose escalation design. The starting dose was 12 mg orally daily for 14 days on and 7 days off. Safety assessments included laboratory evaluations, physical exam, ECOG, vitals, ECG, and adverse events monitoring. Single and multi-dose PK were collected. Results: Three patients (1 with ovarian and 2 with endometrial) were enrolled and completed the initial 21-day safety evaluation period. AL3818 at 12mg/day was found to be safe and well tolerated with no dose-limiting toxicities reported in cycle 1. Only grade 1 and 2 treatment emergent adverse events were noted, including hypertension (htn), oral pain, epistaxis, pain, insomnia, headache, fatigue, tinnitus, sinus tachycardia, anorexia, fatigue, urinary tract infection and urinary frequency. No significant safety concerns were noted. After a single 12 mg dose, the average drug concentration peak time (Tmax) was 10 (4-24) hrs; the average max drug blood concentration (Cmax) was 9.60 (8.47-11.50) ng/mL. After multiple, continuous dosing, the average Tmax was 360 hrs (15 days); average Cmax was 63.80 (52.90-80.30) ng/mL. Because one subject experienced grade 2 htn and one subject experienced grade 3 htn on C2D2, the decision was made that the dose would not be escalated with further cohorts. Conclusions: The recommended phase II dose for AL3818 was determined to be 12 mg daily at 2 wks on/1 wk off regimen. Overall this drug was well tolerated. Blood pressure was manageable with anti-hypertensive medication. Clinical trial information: NCT02558348.
Impact of age, comorbidity, and treatment on survival in elderly women with advanced epithelial ovarian cancer.
Authors: Todd Sarah , Robertson Sharon E. , Xiong Yin , Extermann Martine , Wenham Robert Michael , Chon Hye Sook 
Published: September 2018

e17072 Background: This study aimed to assess the impact of clinical factors, including age and comorbidity, and treatment on outcomes data for women 70 years and older with advanced epithelial ovarian cancer (EOC). Methods: A retrospective chart review was performed on 501 patients with advanced EOC cancer at a single institution between January 1, 2001 and April 1, 2014. Exclusion criteria included non-epithelial histology, stage less than IIIC, and incomplete medical records. Clinical data included disease characteristics, performance measures (ECOG Performance Score, Karnofsky Performance Status, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score), method of treatment and outcome (surgical debulking status, Mayo Surgical Complexity Score, use of intraperitoneal (IP) chemotherapy, total lines of therapy), and survival data. Results: One hundred twenty-six study subjects (25.15%) were > 70 years old at the time of advanced EOC diagnosis. In a univariate analysis, study subjects > 70 years old were significantly more likely to have a higher CIRS-G score, fewer total lines of therapy, no IP therapy, less enrollment in clinical trials, decreased platinum sensitivity, and worse progression free survival (PFS) and overall survival (OS). A multivariate logistic regression analysis, using variables significant to a level of p < 0.1 in the univariate analysis, demonstrated that patients > 70 years old were significantly more likely to have a higher CIRS-G score (OR1.14, p = 0.00037), worse OS (OR0.98, p = 0.00026), and less likely to have IP therapy (OR0.57, p = 0.04973). Factors independently associated with decreased OS in all study subjects in a multivariate cox proportion hazard model were fewer total lines of therapy (HR0.24, p = 0.0035), lack of IP therapy (HR0.64, p = 0.0036), suboptimal debulking status (HR1.38, p = 0.045), lack of platinum sensitivity (HR0.30, p = 0.00001), and older age (HR1.62, p = 0.0016). Conclusions: In this cohort of patients with advanced EOC, elderly patients had worsened OS. This appears to correlate with comorbidity, lack of platinum sensitivity, along with less aggressive treatment options, number of lines of therapy, IP chemotherapy, and clinical trial enrollments.
Preliminary results of the VENUS study: Bevacizumab efficacy and safety in recurrent, platinum-sensitive ovarian cancer—A real-life ambispective study.
Authors: Alexandre Jerome , Launay-Vacher Vincent , Spano Jean-PHilippe , Selle Frédéric , Rey Jean-Baptiste , Brocard Fabien , Floquet Anne , Garnier-Tixidre Claire , Giraud Claire , Morere Jean F. , Patsouris Anne , Pottier Virginie , Raban Nadia , Deray Gilbert , Ray-Coquard Isabelle Laure ,   VENUS Study Group
Published: September 2018

e17093 Background: The aim of the VENUS study was to report on the efficacy/safety of bevacizumab (Bev) in recurrent, platinum-sensitive, ovarian cancer (OC). Methods: VENUS is a multicentric, observational, ambispective study which included both retrospective and prospectice patients (pts). Pts were all naive of any antiVEGF. This analysis presents the results of the retrospective cohort (52 pts) included from 2009 to 2013, with a 3-year follow-up (f/u). Results: Among 148 OC pts included (27 centres), 52 were retrospective. At inclusion, median age: 62.5 years; hypertension according to medical records with or without blood pressure (BP): 30.8%; proteinuria (Pu): 60.0%; abnormal BP (according to NCI-CTCAE 4.03): 71.0%. Mean duration of Bev: 12.7 months. Mean overall survival (OS) and progression free survival (PFS) were respectively 29.4 and 12.9 months. Safety results are presented in the Table. Univariate analysis reported that, at inclusion, Hb<10 g/dL (anemia), ascites and low hematocrit were prognostic of poorer OS. Anemia and TMA (thrombotic microangiopathy) were prognostic of poorer PFS. Multivariate analysis reported that anemia at inclusion was prognostic of poorer OS and PFS. Conclusions: The preliminary results of VENUS (retrospective cohort pts in real life), show that OS and PFS are consistent with what clinical trials reported (29.4 and 12.9 months, respectively). In addition, de novo severe side-effects (grade 3-4 and TMA) were rare, and usual side effects (HTN, Pu) were common but were neither associated with OS nor with PFS. Safety/medical history of VENUS pts. [Table: see text]
Consolidation hyperthermic intraperitoneal chemotherapy for the treatment of advanced stage ovarian carcinoma: A 3-year experience.
Authors: Mendivil Alberto , Abaid Lisa Nicole , Brown John V. , Mori Kristina , Lopez Katrina , Goldstein Bram 
Published: September 2018

e17094 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) potentially confers significant survival benefits in the management of ovarian cancer although the long-term data remain scant. We sought to compare the survival rates of advanced stage ovarian cancer patients who were treated with primary induction therapy alone or in conjunction with consolidation HIPEC. Methods: Sixty-nine ovarian cancer patients who underwent surgery and completed their primary induction chemotherapy were treated with consolidation carboplatin (AUC 10) based HIPEC and compared to a historical cohort that received surgery and primary chemotherapy alone (n=69). The demographic and clinical characteristics in which we were primarily interested included: patient age, body mass index, surgery and pathology data, chemotherapy regimen, toxicity, and progression free/overall survival. Results: The two patient groups were similar in terms of tumor characteristics, cyto-reductive status, distribution of neoadjuvant chemotherapy and number of maintenance chemotherapy cycles administered (P> 0.05). Progression free survival was significantly more pronounced in the HIPEC (25.1 months) patients compared to the control group (20 months) (P=0.024) and there was a decreased risk of disease progression accorded to the patients treated with HIPEC (HR, 2.1028; 95% CI: 1.2941 to 3.4167; P=0.0027). However, we did not discern any HIPEC related overall survival advantages (P=0.29). Conclusions: The results from our ovarian cancer study suggest that adjunctive HIPEC proffers a significant progression free survival advantage and a decreased risk for disease progression. There was, however, no overall survival advantage discerned in the HIPEC group. We also recognize that HIPEC remains controversial and thus, randomized studies evaluating HIPEC compared to standard chemotherapy in the management of ovarian cancer are warranted.
Undifferentiated endometrial sarcomas (UES): Results of a French sarcoma group (FSG) retrospective series of 52 patients (pts).
Authors: Meurer Marie , Floquet Anne , Italiano Antoine , Auriche Morgane , Mancini Julien , Penel Nicolas , Ray-Coquard Isabelle Laure , Delannes Martine , Piperno-Neumann Sophie , Bertucci Francois , Salas Sébastien , Blay Jean-Yves , Pautier Patricia , Duffaud Florence 
Published: September 2018

e17109 Background: UES are rare tumors of very poor prognosis. Although large surgical resection is the cornerstone of curative intent treatment, the optimal post-operative strategy remains unclear. Methods: We conducted a retrospective analysis of UES pts over the last 8 years in 10 FSG centers, from Netsarc and RRePs databases. Results: Fifty-two pts with primary UES treated from 2008 to 2016 were included. The median age was 59 years (range, 42-82), and median ECOG was 0 (range, 0-3): 33 were localized (FIGO I-III) and 19 metastatic at diagnosis. Metrorrhagia, abdominal pain, and pelvic mass bleeding were the most common symptoms. Surgical procedures were radical hysterectomy and bilateral adnexectomy for 23/33 (70%) of localized and 11/19 (58%) of metastatic UES. Metastases were identified post operatively for 9/19 pts. In the localized group, 19 pts (58%) received radiotherapy, 10 (30%) complementary brachytherapy and 9 (27%) adjuvant chemotherapy. In the metastatic group, 16/19 (84%) received chemotherapy (polyCT, n=11). With a median follow-up of 28 months (0.3-112),24/52 pts are alive, 18/33 (58%) localized pts relapsed with 6 local relapses and 11 metastases. The 3- and 5-year Overall Survival (OS) rates were 40.7% and 29.1% respectively, for the whole group. In the localized group; median OS and Relapse-Free Survival (RFS) were 32.7 (23.3-42.1) and 22.9 months (2.3-43.7). In univariate analysis; early FIGO stage (p <0.0001), complete resection (R0-R1 vs R2; p=0.015) and adjuvant radiotherapy (p=0.001) were associated with a better OS; complete resection (p=0.021) and adjuvant radiotherapy (p=0.026) were associated with a better RFS. In the metastatic group, median OS was 16.4 months (12.0-20.7). In univariate analysis, no significant prognostic factor was retrieved neither on OS nor on RFS. Conclusions: Treatment of primary UES is radical hysterectomy and bilateral adnexectomy. Adjuvant radiotherapy appears beneficial for RFS. Due to the rarity and complexity of UES, referring patients to expert sarcoma centers is highly recommended.
Characteristics of very long responder to maintenance cetuximab after a platinum-cetuximab based chemotherapy for recurrent and/or metastatic head and neck squamous cell carcinomas (RM HNSCC).
Authors: Tardy Magalie Pascale , Lescure Celine , Doyen Jerome , Daste Amaury , Lange Martin , Saint-Ghislain Mathilde , Lefebvre Gautier , Sarradin Victor , Bozec Alexandre , Saada-Bouzid Esma , Peyrade Frederic 
Published: September 2018

e17524 Background: Standard treatment for first line RM HNSCC is the association of platinum-5FU and cetuximab. For non-progressive patients (pts), cetuximab is given weekly as maintenance until progression or unacceptable toxicity. In the EXTREME protocol (Vermorken et al, NEJM 2008), this strategy showed an OS of 10.1 months with a mean duration of maintenance of 3 months. This study aimed at describing pts who have benefited from a cetuximab maintenance for a longer period (i.e. > 6 months). Methods: We did a retrospective study in 7 centers in France. Inclusion criteria were: pts > 18 years with a RM HNSCC treated between November 2009 and January 2017, with platinum based chemotherapy and cetuximab followed by weekly cetuximab maintenance of more than 6 months. Results: 53 pts (45 male), with a median age of 57 [38-76] were recorded. Median follow-up was 63.7 months [14.8-237.6]. 72% [37/53] had an oral cavity or oropharynx tumor location with a well or moderately differentiated carcinoma (74%). 45/53 (85%) were smokers and 4/21 (19%) p16 positive. 46/53 (87%) had a Performans Status of 0-1. Mean BMI and albumin level were respectively 22.5 [SD: 4.19] and 40g/l [SD: 4.9]. EXTREME regimen was used for 44 pts, 2 pts had platinum and cetuximab and 7 received platinum, docetaxel and cetuximab. Mean number of chemotherapy cycles was 5 [3-7]. After chemotherapy, the number of pts with complete response (CR), partial response (PR) or stabilization was respectively 5 (9%), 23 (43%) and 25 (47%). 2 pts in PR finally achieved CR during maintenance. One of them stopped cetuximab and was still in CR 5 months later. Mean duration time of maintenance by cetuximab was 11 months [6-24]. Toxicities were mainly cutaneous: 47/53 pts had toxicities, of which 6 had grade 3. Presence of cutaneous toxicities seemed to be correlated with a longer response (p = 0.01). PFS and OS were respectively 15.5 and 27.4 months. Conclusions: Our study allowed us to identify a cohort of long responder pts to maintenance cetuximab including 2 pts who obtained a complete response. More analysis should be done to identify biomarkers able to predict long responder.
Adherence to oral therapies in metastatic castration resistance (m CRPC) prostate cancer patients: The ADOPTA study.
Authors: De la LLave Sandra , Carpeño Laura , Benedetti Johanna , Carles Joan , Puente Javier , Pinto Alvaro , Grande Enrique , Carballido Joaquin , Lorente David , González-Billalabeitia Enrique , Morales Rafael , Gajate Pablo , Alfonso Rosario , Pérez-Valderrama Begoña , Sanchez Gastaldo Amparo , Fernandez Fatima , Calleja Miguel Angel , Duran Ignacio 
Published: September 2018

e18014 Background: With the increasing use of oral anticancer treatments understanding adherence patterns and patient’s information about therapy has become critical. Enzalutamide (ENZ) and Abiraterone acetate (AA) are orally administered drugs approved for the treatment of mCRPC widely prescribed; however, scarce information is available about treatment compliance and patient’s information about these compounds. This study aims to evaluate the adherence to AA and ENZ and the patient’s drug knowledge in mCRPC patients. Methods: A 20-question survey is being delivered to patients with mCRPC receiving either AA or ENZ in 8 centers across Spain. Questions cover items such as demographics, drug information, adherence and perceived benefits among other topics. Surveying is still ongoing. Results: Fifty patients have completed the survey at this time. Mean age is 72 years (range 58-87), educational level is basic in 56 %. Median duration of treatment was 9,5 months. Adherence reported is very high with 84% of the patients taking 100% of prescribed doses and 100% more than 75%. Treatment compliance does not seem to decrease over time despite only 42% of the patients reported the use of devices to secure adherence. A high compliance correlated with better symptom control. Nonetheless, many areas of improvement have been also identified. About a quarter of the patients (26%) ignored the name of the drug they were receiving and 24% whether or not they were in a clinical trial. Almost all patients were not aware of the planned duration of treatment and 70 % recognized that they did not know the consequences of a bad adherence. Eleven patients (22%) were taking AA with food outside of a clinical trial and three patients (6%) reported inadequate dosage (i.e q 12h). Conclusions: While in other diseases adherence to oral therapies has been identified as a potential limiting factor with impact in efficacy, in our series of mCRPC treatment compliance was high and maintained overtime. Yet, serious patient education pitfalls were identified. Data collection is ongoing and further analysis will be presented.
Risk-stratified multidisciplinary ambulatory management of malignant bowel obstruction (MAMBO) program for women with advanced gynecological cancer.
Authors: Lee Yeh Chen , Lheureux Stephanie , Jivraj Nazlin , O'Brien Catherine , Laframboise Stephane , Tinker Lisa Michele , Patel Toral , Stuart-McEwan Terri , Savage Pamela , Easson Alexandra Maria , Croke Jennifer , Lau Jenny , Shlomovitz Eran , Chawla Tanya , Allard Johane , Buchanan Sarah , Ng Pamela , Karakasis Katherine , Oza Amit M. 
Published: September 2018

e18024 Background: Malignant bowel obstruction (MBO) in gynecologic oncology patients is associated with poor prognosis, debilitating symptoms and compromises quality of life. Management of MBO poses a clinical challenge with prolonged hospitalization. Evidence based guidelines for surgical intervention, use of chemotherapy, total parenteral nutrition or best supportive care in this patient population is lacking. Surgical correction may improve survival in selected patients. Retrospective analysis to assess impact of MBO show variable range of MBO-related admissions up to 60 days, and is associated with significant morbidity. Methods: A risk stratified MAMBO program for gynecologic patients has been implemented at Princess Margaret Cancer Centre to define a systematic approach for MBO management and build multidisciplinary consensus for personalized treatment of our patients. The program is novel and includes a nurse-led ambulatory management algorithm with an eHealth application designed to monitor bowel symptoms. A symptom-driven classification system has been devised to objectively define risk using a MBO management algorithm. Complex MBO cases are discussed in designated MBO rounds for consensus treatment recommendation. All patients with MBO are enrolled into a prospective database. Patients undergoing surgical procedures for MBO are consented for opportunistic tissue collection for translational research. MBO patient education materials have been developed to improve awareness and encourage proactive bowel symptom management. Results: Seventy nine patients have been followed through this risk stratified MAMBO program for ambulatory care over 6 months. The MBO program integrates diet, laxatives/stool softeners and drug therapy. Designated MBO rounds are now established for complex case discussion. A prospective MBO database will evaluate treatment and patient-reported outcomes. Conclusions: Risk stratified model of care for multidisciplinary MBO program facilitates decision-making between disciplines and optimize patient care in a vulnerable population with support for ambulatory care.
Increasing the duration and efficacy of intravenous chemotherapy using a patient-centered digital education program: Navigating Cancer’s program for patients receiving pemetrexed for lung cancer.
Authors: Howard Scott C. , Yeatman Timothy Joseph , Watson Mark Layton , Lam Catherine 
Published: September 2018

e18025 Background: Adherence to therapy improves survival in cancer patients. Patient education interventions have effectively improved adherence to oral drugs, but have not been studied for intravenous drugs. Methods: We assessed impact of a pemetrexed educational program for lung cancer patients from 58 oncology practices delivered from 2014-2016 via the Navigating Cancer (www.navigatingcancer.com) patient portal. After online registration, the program provided sequential messages about pemetrexed therapy and management of side effects. Access to each component of the education program was tracked and de-identified data provided to the study team for analysis. Results: Of 944 patients, 441 (47%) accessed pemetrexed-specific educational materials, and were more likely to be Caucasian (p=0.01) and to have never smoked (p=0.05). Patients who accessed educational materials received a mean of 286 days of pemetrexed versus 236 days (p<0.01); their one-year survival was 66% (SE 2.8%) versus 53% (SE 2.9%) (p<0.01). In multivariable analysis, survival was predicted by accessing education (p<0.01), but not race or smoking status (p>0.1). Conclusions: Drug-specific patient education delivered via a patient portal and email reached 47% of registered patients and was associated increased duration of therapy and improved survival. [Table: see text]
Enrolment of adolescents and young adults with cancer (AYAWC) to clinical trials at the Children’s Hospital of Eastern Ontario (CHEO).
Authors: Lum Sarah , Laforest Isabelle , Tang Kenneth , Abbott Lesleigh S. 
Published: September 2018

e18043 Background: Five-year survival among AYAWC has seen less improvement than in other age groups. One hypothesized reason is low accrual to clinical trials, for which the reasons need further determination. Our objectives were to determine the enrolment of AYAWC on treatment clinical trials at CHEO, a tertiary care pediatric hospital in Ottawa, Canada and to determine barriers to enrolment of AYAWC compared to younger patients. Methods: A retrospective chart review of patients diagnosed at CHEO over 10 years from January 1, 2006 to December 31, 2015 was performed. AYAWC included 15-18 year olds, and younger patients included 0-14 year olds. Patients 18 years and older are treated at adult centers. The number of patients enrolled on an upfront treatment clinical trial was collected while those not enrolled were reviewed for documented non-enrolment reasons. Clinical trials available at CHEO during this time period were also recorded. Results: A total of 733 patients were diagnosed with 96 AYAWC and 637 younger patients. The proportion of patients enrolled on clinical trials was 19.8% (19) AYAWC and 27.3% (174) younger patients (p = 0.12). Trials were not available for 57.3% (55) of AYAWC and 53.7% (342) of younger patients for their disease type (p = 0.51). For the remaining 41 AYAWC, 46.3% were enrolled. For AYAWC not enrolled, 40.9% had a reason documented: for 22.2% a physician felt it was not in the patient’s best interest, 44.4% did not meet eligibility, 33.3% of families/patients declined. For the remaining 295 of younger patients that had trials available, 59% enrolled on a trial. For younger patients not enrolled, 25.6% had another reason documented: for 25.8% a physician felt it was not in the patient’s best interest, 45.2% did not meet trial eligibility, 25.8% of families/patients declined, 3.2% other reason. Conclusions: There were fewer AYAWC enrolled on trials compared to younger children. There were not fewer trials available for AYAWC patients than younger children. For patients not enrolled, the majority did not have an open trial available and otherwise, reasons for non-enrolment did not differ significantly between groups. Next steps could include data from local adult centers.