tbuckley/cabot-search huggingface dataset:
Absence of interaction of cabazitaxel on the pharmacokinetics of midazolam: Results of a drug–drug interaction study in patients with advanced solid tumors.
Authors: Olivier Rixe, John Sarantopoulos, Chung-Tsen Hsueh, A. Craig Lockhart, Sharona Ross, Sanjiv S. Agarwala, Wendy Zhang, Jian Y. Yin, Claudine Wack, Florent Mazuir, Jayne S. Gurtler
Journal: Journal of Clinical Oncology (2013)

126 Background: Cabazitaxel (Cbz) is approved in combination with prednisone/prednisolone for the treatment of men with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen. In vitro studies showed that Cbz is mainly metabolized through CYP3A, resulting in inhibition of this family of enzymes. Midazolam (Mdz) is primarily metabolized by CYP3A4. We aimed to determine the effect of Cbz on CYP3A activity by comparing the pharmacokinetic (PK) properties of Mdz when administered alone and following co-administration with Cbz. Methods: An ongoing safety and PK study of Cbz in patients with metastatic or locally advanced solid tumors and varying degrees of hepatic impairment (NCT01140607) included a cohort with normal hepatic function to assess the effect of a single Cbz dose on the PK profile of a single dose of Mdz. This was an open-label, two-period, fixed-sequence study in patients aged between 45 and 60 years with advanced solid tumors and normal hepatic function. A single dose of Mdz (2 mg) was administered orally alone (Day –1) and at the end of a 1-hour infusion of Cbz (25 mg/m 2 ) (Day 1), with a 24-hour interval between the two administrations of Mdz. Endpoints included AUC and AUC last of Mdz with and without Cbz administration, and safety evaluations. Results: Of the 13 patients enrolled and treated in the cohort, 11 patients were included in the PK analysis. Exposure (AUC and AUC last ) and other PK parameters after a single administration of Mdz alone and in combination with Cbz (Day 1) were similar. The AUC ratio for Mdz administered alone or with Cbz was 0.97 (90% CI: 0.76–1.23). The AUC last ratio for Mdz administered alone or with Cbz was 1.04 (90% CI: 0.81–1.34). All 13 patients had ≥1 adverse event (AE), 11 (84.6%) experienced a Grade 3–4 AE, and 4 (30.8%) experienced a serious AE. The majority of Grade 3–4 AEs were haematological and no new or unexpected safety findings were observed. Conclusions: In this study, Cbz did not increase the plasma exposure of Mdz. This indicates that Cbz is not a CYP3A inhibitor in the clinical setting and can be administered in combination with drugs metabolized by CYP3A. Clinical trial information: NCT01140607.
Cost of treatment failure in patients with chronic lymphocytic leukemia: Results of a large U.S. observational study.
Authors: Mekre Senbetta, Marie-Noelle Robitaille, R. Scott McKenzie, Patrick Lefebvre
Journal: Journal of Clinical Oncology (2014)

22 Background: Patients with chronic lymphocytic leukemia (CLL) who eventually experience disease progression are offered a limited choice of treatments. This retrospective observational study assesses healthcare resource utilization and costs in patients with CLL who have received one prior therapy and experience treatment failure (TF). Methods: Adult patients with ≥1 diagnosis of CLL and ≥1 claim for a medication used to treat CLL were identified in the IMS PharMetrics Plus database (01/2008 – 09/2013). Patients were excluded if they had evidence of a non-hematologic malignancy, used a non-CLL antineoplastic agent, or received a stem cell transplant during the 12-month baseline period. TF was identified based on earliest occurrence of one of the following events: initiation of a new treatment for CLL that was not part of the 1st-line therapy, resumption of any CLL treatment following a minimum of 3-month break in treatment, stem cell transplant, radiotherapy, hospital mortality, or hospice care. Resource utilization was reported as monthly incidence rates, and costs were reported in 2013 $US per patient per month (PPPM), comparing patients with and without TF. Results: A total of 6,015 patients with CLL were identified (mean patient age: 63 years old; proportion female: 36%), of which 2,734 (45%) experienced TF. Patients with TF tended to require more OP visits (3.2 vs. 2.5). Average total cost PPPM was $7,850 for patients with TF and $4,555 for patients without TF. The main cost drivers were outpatient (OP) costs ($4,355 for patients with TF; $3,022 for patients without TF) and hospitalization costs ($2,659 for patients with TF; $1,038 for patients without TF). Once adjusted for baseline characteristics, average total cost difference between patients with and without TF was $3,757 PPPM. This difference was largely due to hospitalization (45%) and to OP costs (46%). Conclusions: Patients with CLL experiencing TF appear to require more OP visits and to be associated with higher OP and hospitalization costs PPPM compared to those without TF. These data help in our understanding of the healthcare resource utilization and costs associated with the treatment of patients with CLL.
Gastric cancer new nomograms based on preoperative clinical prognostic factors.
Authors: Etsuro Bando, Michael W. Kattan, Makoto Ohori, Masanori Tokunaga, Yutaka Tanizawa, Taiichi Kawamura, Masanori Terashima
Journal: Journal of Clinical Oncology (2014)

12 Background: Nomogram has been developed and shown to be more accurate than the conventional staging systems for predicting prognosis in gastric cancer patients. Preoperative clinical staging is a primary measure with which therapeutic strategies for gastric cancer is determined. While many reports have been published on the relationship between nomogram based on pathologic factors and survival outcomes, there were no reports of developing nomogram based on preoperative clinical factors. The purpose of this study was to firstly build a specific nomograms based on preoperative clinical prognosticators for predicting overall survival (OS) and disease-specific survival (DSS) in patients with primary gastric cancer for choosing accurate therapy preoperatively. Methods: We included patients with primary 2,807 gastric cancer patients, who had not been undergone prior chemotherapy, between 2002 and 2010. The priori chosen pre-operative prognostic covariates were sex, age, tumor site, tumor size, histologic subtype obtained by endoscopy, endoscopic macroscopic appearance, tumor depth, numbers of positive nodes and distant metastases on CT scan, and serum concentration of CEA/CA19-9. Internal validation was performed by applying the nomograms to the patients of an internal cohort calculated by bootstrap re-sampling method. The model's discriminative ability was estimated by means of Harrell’s C statistics. Results: At a median follow-up of 57 months, 612 deaths and 523 cancer-related deaths were recorded. Five-year OS and DSS rates were 64.3% and 72.4%. In Cox regression, depth and nodal involvement is the most powerful independent prognostic factors. And type4 is identified negative prognosticators. Sex and serum tumor markers have little effectiveness for survival outcome. The bootstrap-corrected Harrell’s C statistics for OS and DSS of our nomograms were 0.852 and 0.880, which was higher than that of TNM seventh edition (C=0.826, 0.822) or that of sixth edition (C=0.822, 0.801). Conclusions: These nomograms accurately predict OS and DSS of Japanese gastric cancer patients pre-operatively. Worldwide external validation should be necessary for practical use of our nomograms instead of TNM classification.
Phase I/II trial of neoadjuvant chemoradiotherapy with 5-FU, cisplatin, mitomycin C, and heparin for borderline resectable pancreatic cancer.
Authors: Taizo Hibi, Minoru Kitago, Koichi Aiura, Minoru Tanabe, Osamu Itano, Masahiro Shinoda, Yuta Abe, Hiroshi Yagi, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2013)

315 Background: Because of the high incidence of local recurrence and liver metastasis, long-term outcomes of patients following resection of advanced pancreatic cancer are extremely poor. Facilitation of curative resection and prevention of micrometastasis are the goals of neoadjuvant therapy. We evaluated the feasibility and efficacy of our neoadjuvant chemoradiotherapy (NACRT) protocol for borderline resectable pancreatic cancer patients. Methods: During the period between 2003 and 2011, 24 patients with borderline resectable pancreatic cancers underwent NACRT comprising 5-FU (300 mg/body/day, day 1−5/week for 4 weeks), cisplatin (10mg/body day2, 9, 16, 23), mitomycin C (4mg/body/day, day 1, 8, 15, and 22), heparin (6000 IU/body/day for 4 weeks), and radiation (2 Gy/day, day 1−5/week for 4 weeks, total 40 Gy). They were reevaluated for resectability after therapy. Primary endpoints were toxicity and overall patient and disease-free survivals. Secondary endpoint was the ratio of microscopically margin negative resection. Results: All 24 patients completedNACRT. Grade 3−4 hematological adverse events were observed in 9 (38%) patients but none developed severe gastrointestinal toxicity. In 7 (29%) patients, restaging revealed distant metastasis or local disease progression not amenable to curative resection. The remaining 17 patients (71%) underwent surgery (pancreatoduodenectomy, 13 and distal pancreatectomy, 4) with zero 30-day postoperative or in-hospital mortality. The 5-year overall all patient and disease-free survival rates after pancreatectomy were 52.6% and 36.3%, respectively. Postoperative histopathological evaluation demonstrated a marked degenerative change in the specimen, achieving negative surgical margins in 15/17 (88%) patients and pathological complete response in the remaining 2 (12%) patients. Conclusions: Our NACRT protocol is feasible with a low toxicity profile and an excellent curative resection rate in the treatment of borderline resectable pancreatic cancer. It is a promising regimen associated with improved long-term prognoses than historical controls.
Factors associated with toxicity-related service use among community oncology patients.
Authors: Jordan M Harrison, Beth Lavasseur, Philip J. Stella, Paul T. Adams, Lauren Swafford, JoAnn Lewis, Kari Mendelsohn-Victor, Christopher Ryan Friese
Journal: Journal of Clinical Oncology (2016)

133 Background: Chemotherapy-associated toxicities occur often, yet sparse data are available to correlate toxicities with related service use. Toxicities may disrupt treatment, impair quality of life, and induce unplanned service use. We sought to understand the frequency and correlates of unplanned service use among patients receiving first-cycle chemotherapy at 5 community-based ambulatory oncology practices in southeast Michigan. Methods: A prospective survey examined the dichotomous outcome of toxicity-related unplanned service use. Newly-diagnosed patients were recruited before the first chemotherapy cycle. At the second cycle visit, patients completed a questionnaire that measured severity of nausea, vomiting, diarrhea, constipation, mouth sores, IV catheter problems, pain, fever/chills, extremity edema, and dyspnea on a 5-point scale (1 = did not experience to 5 = disabling). They also rated distress on a 10-point scale (0 = none, 10 = worst). Patients reported unplanned oncologist visits, emergency department visits, and unplanned hospitalizations, all of which were treated as unplanned service use. Mixed-effects logistic regression was used to identify factors associated with unplanned service use, with random effects for each clinic. Results: Among 106 patients (98% white, 74.5% women, mean age 60+11), common diagnoses were breast, lung, and colorectal cancer and non-Hodgkin lymphoma. Frequent toxicities were pain, nausea, diarrhea, and constipation. Thirty-six patients (34%) reported unplanned service use: 29% reported oncologist visits, 14% reported ED visits, and 8% reported hospitalizations. 45% of the total sample and 89% of patients with unplanned service use reported at least one toxicity that was severe or disabling. Factors associated with unplanned service use were high patient-reported distress and receipt of colony-stimulating factor. Conclusions: Toxicity-related service use was common in this community oncology population. Proactive symptom assessment tools may help clinicians manage toxicities between visits. A deeper understanding of toxicity patterns and correlates can inform clinical practice guidelines in community oncology practices.
Aflibercept in combination with FOLFIRI for the second-line treatment of patients with metastatic colorectal cancer: First interim safety data from AFEQT trial.
Authors: Meher Ben Abdelghani, Christophe Borg, Louis-Marie Dourthe, Gael Deplanque, Julien Taïeb, Jean-Philippe Metges, Philippe Laplaige, Veronique Lotz, Amele Amrate, Gérard Lledo
Journal: Journal of Clinical Oncology (2015)

661 Background: In the randomized phase 3 VELOUR trial, aflibercept + FOLFIRI demonstrated a statistically significant overall survival benefit compared with FOLFIRI alone in metastatic colorectal cancer (mCRC) patients (pts) previously treated with an oxaliplatin-based regimen. Evidence from the VELOUR trial supported the initiation of a French clinical trial; AFEQT [NCT01670721] to capture utility values from QoL instruments and collect safety data from a target population similar to that in VELOUR. Interim data collected by French investigators are reported. Methods: AFEQT is single-arm, open-label trial evaluating safety and health-related QoL of aflibercept in mCRC pts previously treated with an oxaliplatin-based regimen. Estimated total enrollment is 200 mCRC pts. Eligible pts received aflibercept (4 mg/kg) q2wks on day 1 of each cycle followed by FOLFIRI up to disease progression, unacceptable toxicity, death, or investigator/patient decision, whichever occurred first. FOLFIRI starting dose and subsequent additional dose modifications were at the discretion of the treating physician. Safety assessments followed each cycle and continued until 30 days after last drug administration. The percentage of pts with grade 3/4 adverse events (G3/4 AEs) in the safety population of AFEQT was compared with that of VELOUR. Results: At data cut-off, the safety population comprised 123 pts with at least 1 completed cycle of treatment. Median age of pts was 64.6 vs. 61 years in VELOUR. At least 1 G3/4 AE was experienced by 67.5% of pts vs. 83.5% in VELOUR. Most reported G3/4 AEs were G3. There were no reports of G4 hypertension or diarrhea. Additional data will be reported during the meeting. Conclusions: In VELOUR, AEs occurred early in treatment, were often of single occurrence, generally reversible, and consistent with AEs commonly seen by oncologists. Interim safety analysis from AFEQT did not identify any new safety signal. Clinical trial information: NCT01670721. [Table: see text]
Cancer-related knowledge in relatives of cancer patients and general public in Istanbul, Turkey
Authors: N. S. Turhal, C. Ulus, S. Sari, N. Senturk, D. Bingol
Journal: Journal of Clinical Oncology (2008)

20650 Background: The word myth comes from the word “mitos” in French, involves the false information that is presumed to be correct by the community although there is no scientific basis. There are many myths about cancer in Turkey just as in the rest of the world. There are very few studies that evaluate public knowledge about cancer in our country. The goal of our research is to measure knowledge of cancer in community. In addition, difference between knowledge of participants who have relatives with cancer and who do not and finding out where they get information that they have. Methods: This is a cross-sectional study. Data is obtained from a total of 415 participants, of which 244 are female, who were treated at Marmara University Faculty of Medicine Hospital (MUFMH). We gave them a questionnaire that has three parts that include their socio-economic features, questions about cancer and the source where this information is obtained. Data are examined for dispersion frequency. Chi-square test is used for comparison of classified data, t-test is used for comparison of continuous variables. After the questionnaire is completed, a brochure that contains correct answers is given to participants. Results: The mean age of the participants is 41,17±15,40 (sd). 271 of our participants stated that they are related with one or more cancer patient in their close family. 70,1% of participants have had high school or more education. 61,5% of them knew that breast cancer is not only seen in females. 53,9% of participants who have relatives with cancer, and 31.9% of participants who do not, answer correctly by stating that cancer is not always painful (p<0.05). The proposition that all cancer patients die from cancer is answered as no in a proportion of 79%. Although mobile phones are not demonstrated to cause cancer scientifically, our participants think in high proportions that mobile phones cause cancer. Conclusions: The proportion of false knowledge about cancer is unacceptably high in our cohort. To our disappointment, participants who have relatives with cancer do not have more correct knowledge than participants who do not. Although we have informed a small part of the community by the brochure we have delivered, the efforts should increase to inform general community about cancer. No significant financial relationships to disclose.
The impact of patient characteristics on voiding symptoms, irritative symptoms, and sexual function, following stereotactic body radiotherapy for prostate cancer.
Authors: Zaker Hamid Rana, Robert Hong, Donald McRae, Gregory Bernstein, Robert Mordkin, Nadim Munir Nasr
Journal: Journal of Clinical Oncology (2015)

245 Background: Urinary symptoms and sexual dysfunction are the two most common complaints following prostate radiotherapy. There is limited clinical data evaluating the impact of baseline patient characteristics on response to hypofractionated treatment. This study sought to evaluate how patient age and prostate size affects voiding symptoms, irritative symptoms, and sexual function, following stereotactic body radiotherapy (SBRT). Methods: This retrospective analysis includes 102 non-metastatic patients treated with SBRT at a single institution between May 2008 and September 2014. The course of radiotherapy consisted of 36.25 Gy (range 35–40) over 5 daily fractions. International Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) were recorded at baseline, 1, 3, 6, 9, 12, 18, 24, and 36 months after treatment. Results: Median patient age was 68 years old (range 47-88) and median prostate volume was 43 cc (range 18.7-170.7). Baseline IPSS irritative score, IPSS voiding score, and SHIM score were 5.34, 5.42, and 13.55. A statistically significant increase in voiding (7.02), irritative (7.21), and decrease in SHIM score (11.77) was observed after one month (p &lt; .05). The IPSS irritative score and IPSS voiding scores returned to baseline in &gt;90% of patients by 9 months and SHIM scores returned to baseline in &gt;90% of patients by 2 years. Prostate size ≤ 50 cc showed higher baseline IPSS voiding and irritative resolution rates after 3 months (p &lt; .05). Conclusions: While an increase in IPSS irritative score, and a decrease in SHIM score initially occurred, all symptoms return to baseline within three years. Age did not affect urinary or sexual dysfunction following radiotherapy. Patients with smaller prostate volumes had significantly better voiding and irritative outcomes when compared to larger volumes.
Impact of screening and treatment on racial and ethnic differences in health service use, cost, and mortality among advanced (T3 or greater) prostate cancer patients.
Authors: S. Bruce Malkowicz, Sumedha Chhatre, Sanford Schwartz, Ravishankar Jayadevappa
Journal: Journal of Clinical Oncology (2014)

131 Background: Limited information is available regarding the association between race/ethnicity, health service use, cost, and mortality in older patients with advanced (T3 or greater) stage prostate cancer. The objective is to analyze the race/ethnic differences in mortality, cost, and assess the mediating effect of prostate cancer screening and treatment on these differences in fee-for-service Medicare patients with advanced prostate cancer Methods: Retrospective, observational, case-control study using SEER-Medicare linked data. Cohort consisted of 15,054 elderly men diagnosed with advanced stage prostate cancer between 2001and 2004 and followed retrospectively for up to 2009. Cancer-free controls from Medicare data were used to determine the incremental cost of advanced stage prostate cancer. Racial/ethnic variation in health service use, cost, and mortality were analyzed using Poisson, GLM log-link, and Cox regression models. Results: For the age 66 to 75 and 76 to 85, age groups, racial/ethnic differences in health service use, cost, and all cause mortality were observed. Blacks were less likely to have received prostate cancer screening in the year prior to diagnosis of advanced prostate cancer, less likely to have received any treatment after diagnosis and had higher disease specific mortality. After adjusting for prostate cancer screening and treatment across age groups however, odds of prostate cancer-specific mortality were comparable between racial/ethnic groups suggesting that screening may have some mitigating effect on outcomes in the AA population HR 1.23 (1.07-1.41) versus HR 1.12(0.98-1.29). Conclusions: The pattern of racial/ethnic disparity varies by age group with higher mortality among black men. This may be attributable to disparity in prostate cancer screening or treatment. This suggests that the lack of consideration for racial considerations in the U.S. Preventive Services Task Force PSA recommendations could have disparate racial impact.