tbuckley/cabot-search huggingface dataset:
A phase I dose-escalation trial evaluating ARQ 197 administered in combination with sorafenib in adult patients (pts) with advanced solid tumors.
Authors: A. A. Adjei, J. A. Sosman, G. K. Dy, W. Ma, G. J. Fetterly, D. Skupien, J. A. Means, R. Savage, F. Chai, I. Puzanov
Journal: Journal of Clinical Oncology (2010)

3024 Background: ARQ 197 (A) is a selective non-ATP competitive inhibitor of c-MET, a RTK implicated in tumor cell proliferation, invasion and angiogenesis. Maximum tolerated dose (MTD) and recommend phase II dose (RP2D) of A in monotherapy and in combination with erlotinib were reported previously. Based on preclinical synergy of A in combination with sorafenib (S) in a number of cell lines, a phase I study was undertaken to define safety and RP2D of A+S combination. Secondary objectives include evaluation of pharmacokinetics (PK) and biomarkers (HGF, VEGF, soluble c-MET). Methods: A traditional 3+3 dose escalation schema was employed. An initial cohort was treated at dose level (DL) 1 (A 360 mg PO BID + S 200 mg PO BID). With no DLT observed at this DL, dosing was escalated to DL2 (A 360 mg BID + S 400 mg BID), which represents full single-agent doses of both drugs. Results: To date, 14 pts (2 F/12 M; mean age: 58.7 yrs) have been treated at the 2 DLs, 5 in DL1 w/o DLT and 9 in DL2 with 1 experiencing 2 DLTs [grade (G) 3 fatigue and G3 dyspnea]. Accordingly, DL2 is the RP2D. No A-related serious adverse events (AEs) or G4 AEs were reported. G3 A-related AEs have been reported in 4/14 pts (29%) (fatigue, dyspnoea, dry skin, musculoskeletal chest pain, hyperbilirubinaemia 1 each); G1/2 in 7 pts (50%) (2 fatigue, thrombocytopenia, lymphopenia, diarrhea, nausea, vomiting, abdominal tenderness, AST increased, anorexia, nipple pain, and rash 1 each). PK analysis of A showed that on day 1 mean Cmax(n=8) was 1766 ± 1452 ng/mL and mean AUC(0-12) was 14053 ± 13736 hr*ng/mL. On day 29 mean Cmax (n=6) was 1986 ± 1487 ng/mL and mean AUC(0-12) was 15,003 ± 13428 hr*ng/mL. Nine of 14 pts are evaluable for efficacy with 6/9 (67%) demonstrating a best RECIST response of stable disease (8+ to 29+ wks) including 1 renal cell carcinoma pt with 22% tumor regression. Conclusions: The combination of A + S is safe and well tolerated, with 360 mg PO BID A + 400 mg PO BID S recommended for subsequent phase II evaluation. PK parameters indicated that S had no effect on the disposition of A. Preliminary evidence of anticancer activity has been observed, indicating that the combined inhibition of c-MET and angiogenic signaling has therapeutic potential. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ArQule ArQule
UK children are more than twice as likely to be obese than previous generations, figures show
Authors: S. Mayor
Journal: BMJ (2015)

<h3>Objectives</h3> The UK human papilloma virus (HPV) vaccination programme requires 80% uptake to have a significant impact on cervical cancer rates. Uptake in the first three years of the programme was 66%. We report the results of a cross-sectional survey of young women attending sexual health services (SHS) in England, reviewing HPV vaccination uptake and prevalence of HPV-related risk factors. <h3>Methods</h3> An anonymous questionnaire surveyed women aged 13–19 attending 19 hospital-based and 13 community-based SHS across England, March–August 2011. Data were analysed using multiple logistic regression. <h3>Results</h3> 2247 questionnaires were completed. Compared with national data, respondents had higher smoking rates (48% vs 14% of 15 year olds), coitarche under-16 (52% vs 38%), previous sexually transmitted infections (STIs) (25% vs 4%) and a higher proportion not in education, employment or training (NEETs) (8% vs 2% of 16 year olds). Seventy-four per cent had been offered the vaccination, with significantly lower offer rates in London, non-white ethnicities, 17–19 year olds, NEETs, smokers and those with previous STIs (all p&lt;0.05 in multivariate analysis). Sixty-five per cent of those offered, completed, with significantly lower completion rates in London, non-white ethnicities, 17–19 year olds, NEETs, smokers and those with previous STIs (all p&lt;0.05 in multivariate analysis). Overall completion rate was 47%. <h3>Conclusions</h3> We observed lower vaccination offer and completion rates and higher prevalence of HPV-related risk factors compared with national data. The highest risk individuals were the least likely to have been offered or to have completed the course. This survey highlights an opportunity for primary prevention by routinely offering the HPV vaccine to eligible women attending SHS.
Symptoms experienced by fatigued patients receiving chemotherapy for cancer: A URCC CCOP study
Authors: J. T. Hickok, G. R. Morrow, J. A. Roscoe, J. J. Kirshner, J. N. Atkins, L. K. Colman, J. L. Lindke, R. Hill
Journal: Journal of Clinical Oncology (2004)

8092 Background: Fatigue is reported by 80–100% of patients undergoing cancer chemotherapy. Patients were queried about specific fatigue symptoms. Methods: 389 cancer patients who reported fatigue on a 10 cm. Visual Analogue Scale (VAS) (1 = ‘Not at all’ and 10 = ‘A great deal.’) during chemotherapy completed the Fatigue Symptom Checklist (FSCL) 5–7 days following their first 4 cycles. The FSCL measures the severity of 30 symptoms on a 5 point scale headed “At the moment I feel:” (1 = ‘absence of [the symptom]’ and 5 = ‘a great deal.’) Three subscales of 10 items each, (drowsiness, concentration, physical symptoms) and a total score were calculated. Results: The most common cancers were breast (56%), hematologic (13%), lung (12%), gynecologic (8%) and alimentary (6%). 76% were female and 73% of women had breast cancer. The average age was 54 for females and 61 for males. 90% were Caucasian and 6% African American. Division of patients into two groups based on the VAS fatigue score at each cycle, (2–5 = ‘less fatigued,’ and 6–10 = ‘more fatigued’) showed significant differences between total and subscale scores by degree of fatigue (all Ps < 0.001). “Feeling tired over my whole body”, “Tired in my legs”, and “Want to lie down” from the drowsiness subscale were the most severe symptoms in both groups. More fatigued patients felt these symptoms “a moderate amount” (e.g. cycle means for “tired over my whole body” were 3.1, 3.4, 3.2, and 3.1), while those who were less fatigued felt them “a little” (cycle means = 1.8, 2.3, 1.9, and 1.9). Drowsiness was the next most severe symptom. Cognitive impairment and physical symptoms were less severe. There were no significant differences in scores by gender or age group, divided at the median age of 55. Patients with lung cancer reported the most severe symptoms at all four cycles, and those with cancers of the alimentary tract reported the least severe symptoms. Conclusions: Weakness and drowsiness most often characterize the fatigue experienced by patients receiving chemotherapy, suggesting that interventions to increase stamina and improve sleep quality may be beneficial. Supported, in part, by NCI PHS grant U10 CA37420 and by ACS grant RSG-01-071-PBP No significant financial relationships to disclose.
Response to sirolimus in combination to tirosine kinase inhibitors (TKI) in three cases of PDGFRA-D842V metastatic gastrointestinal stromal tumor (GIST)
Authors: C. Piovesan, E. Fumagalli, P. Coco, E. Palassini, P. Dileo, C. Morosi, A. Gronchi, P. Casali
Journal: Journal of Clinical Oncology (2009)

10565 Background: In GISTs, specific KIT/PDGFRA mutations lead to differential drug sensitivity. The exon 18 PDGFRA-D842V mutation is known to be resistant to imatinib and sunitinib. Activation of tyrosine kinase receptor involves a signal transduction pathway involving AKT/mTOR, RAS, phosphoinositide 3-kinase and BRAF. We therefore used the mTOR inhibitor sirolimus in three pts with a PDGFRA-D842V metastatic GIST. Methods: Since August 2007, 3 PDGFRA-D842V GIST pts (age: 54–56–63 yrs) have been treated with sirolimus (2–3 mg/day) in combination to TKI (PKC412 in one pt, and imatinib in 2 pts), on an individual use basis. Two pts were progressing on imatinib, while the third pt was treated with imatinib + sirolimus upfront. Sirolimus blood levels were assessed. Results: Two pts had a Choi's response 6 and 3 mos, respectively, after starting the combination. In the first pt, responding to sirolimus + PKC412, the latter drug had been started alone, with no response. The last pt, undergoing imatinib + sirolimus, has a short follow-up. Disease was stable at 2 mos, although clinical improvement was noticed, and therapy is ongoing. The first pt underwent surgery of residual peritoneal disease after 13 mos, and is now continuing therapy being surgically NED. The other pt had a tumor progression after 9 mos from starting therapy and 6 mos from tumor response (with a negative PET scan). Treatment was relatively well tolerated, with skin toxicity in one pt. Conclusions: PDGFRA-D842V GIST are poorly responsive to TKI. We saw signs of antitumor activity in 3 pts with this mutation by combining TKI (imatinib or PKC412) with sirolimus. Tumor response was seen following some months of therapy. Studies are warranted. [Table: see text]
Bone mineral density in childhood cancer survivors (CCS).
Authors: A. C. Dietz, L. Polgreen, A. Petryk, W. Leisenring, P. Goodman, D. A. Mulrooney, L. Steffen, A. Kelly, K. S. Baker, J. Steinberger
Journal: Journal of Clinical Oncology (2010)

9157 Background: Decreased bone mineral density (BMD) has been reported in childhood cancer survivors (CCS). However, factors associated with low BMD in CCS are not well characterized. Objective: To identify factors associated with low BMD (Z-score ≤ −1) in CCS. Methods: In a cross-sectional study of CCS. BMD was determined by dual-energy x-ray absorptiometry. All patients underwent growth hormone (GH) stimulation testing. Multivariable logistic regression was utilized to evaluate relations between anthropometrics, endocrine function, and treatment history with BMD, adjusted for bone age and gender. Results: Of 284 CCS patients, 41 were excluded due to previous diagnosis of GH deficiency (GHD) and/or treatment with GH, leaving 243 subjects (54% males), median age 15.1 years (range 9.5-18.0 years), surviving 5.4-17.8 years after cancer diagnosis. 21% GHD and 0.8% had gonadal failure. 21% had low lumbar spine (L2-L4) BMD and 6% had low total body less head (TBLH) BMD. Brain irradiation (yes vs. no; Odds ratio [OR] 3.8; 95% confidence interval [CI] [1.0, 15.6]), cumulative prednisone equivalent dose (≥ 6350 vs. 0 mg; OR 4.8; CI [1.7, 14.2]), lower lean body mass (LBM) Z-score (per standard deviation (SD); OR 1.8; CI [1.2, 3.0]), and GHD status (yes vs. no; OR 2.8; CI [1.1, 6.7]) were associated with low L2-L4 BMD (adjusted for height, Tanner stage, and age). Lower LBM Z-score (per SD; OR 4.5; CI [1.9, 12.5]) and increased time since diagnosis (>10 vs. 5-10 years; OR 3.8; CI [1.1, 14.3]) were associated with low TBLH BMD (adjusted for height). Conclusions: In CCS, lower LBM, higher cumulative steroid exposure, history of brain irradiation, longer time since diagnosis, and GHD were associated with low BMD. LBM and GHD are the only modifiable risk factors for low BMD. Weight-bearing physical activities and early treatment of GHD to increase BMD are recommended in CCS. No significant financial relationships to disclose.
Non-myeloablative stem cell transplant: A dose-finding study
Authors: D. Bron, Augustin Ferrant, P. Zachee, Johan Maertens, Chantal Doyen, P Van den Berghe, L. Noens, W. Schroyens, D. Selleslag, H. Demuynck, A. Triffet, A De Meuter, M. Boogaerts
Journal: Blood (2002)
A comparison of patient and physician attributes that promote patient involvement in treatment decision making in the oncology consultation
Authors: P. M. Ellis, S. J. Dimitry, M. A. O’Brien, C. A. Charles, T. J. Whelan
Journal: Journal of Clinical Oncology (2006)

6098 Background: Cancer patients have indicted a desire to be more involved in treatment decision making (TDM). However, little is known about the attributes of patients, physicians and their interaction that promotes patient involvement in TDM in the oncology consultation. This study compared attributes generated by patients and physicians that make it easier for patients to be involved in TDM. Methods: Semi-structured interviews were undertaken with 19 patients with cancer (lung, breast, prostate, GI) and 21 medical and radiation oncologists at a regional cancer centre. Participants were asked to identify attributes of physicians, patients and their interaction that promotes patient involvement in TDM. Interview transcripts were independently coded by 2 analysts using decision rules to identify specific attributes. Attributes identified by each analyst were compared and a high level of agreement was found. The analysts then independently compared the physician and patient generated lists and identified common vs unique items. There was a high level of agreement on which attributes were common to both lists versus unique. Results: Oncologists identified 173 physician, 59 patient and 9 interaction items. Patients identified 50 physician, 42 patient and 11 interaction items. Patients and physicians identified 17 common physician items, 29 common patients items and 1 common interaction item. Physicians identified 138 more attributes than patients, most of which were physician related. Common patient attributes centred on information seeking (eg prepare for the consultation by reading, be aware of all treatment options and question the options). Common physician attributes focused on specific communication behaviors (eg, make eye contact, tailor information to patient needs, be direct with patients, ensure patient understands information). The common interaction item was to keep the discussion informal. Conclusions: Patients and physicians appear to have different ideas about what is important to promote patient involvement in TDM. Many of the attributes identified can be easily incorporated into current practice. There is a need to develop and evaluate communication skills training to promote patient involvement in TDM. No significant financial relationships to disclose.
Dose-ranging study of the combination of paclitaxel poliglumex and pemetrexed in advanced non-small cell lung cancer (NSCLC)
Authors: B. M. Slagle, J. R. Rigas, K. H. Dragnev, I. Williams, W. DiSalvo, C. Engman, B. Lipe, S. Simeone
Journal: Journal of Clinical Oncology (2009)

e19090 Background: Taxanes continue to play an important role in the treatment of advanced NSCLC. Paclitaxel poliglumex (XyotaxTM) is an ester α-poly-L-glutamic acid conjugate of paclitaxel allowing for solubility in aqueous solution, not requiring Cremophor or ethanol for intravenous administration or premedications. This is a non-randomized single-arm, single-institution open label dose-ranging study was designed to evaluate the combination of pemetrexed and paclitaxel poliglumex. Methods: The primary objective of this study was to evaluate the safety of this combination. Patients (pts) were enrolled in 2 different dosing levels. The first 6 received 135 mg/m2 paclitaxel poliglumex and 500 mg/m2 pemetrexed intravenously every 3 wks. None of the 6 pts experienced an initial dose limiting toxicity (IDLT) following 2 cycles of therapy and the paclitaxel poliglumex was then escalated to 175 mg/m2 with 500 mg/m2 pemetrexed. Eligibility included advanced NSCLC, one or more measurable lesions (RECIST), ECOG = 0–2, prior chemotherapy and radiation allowed, no grade 2+ peripheral neuropathy, no untreated brain metastases, and no active cardiac disease. Results: Twelve pts were enrolled, 6 pts to each dose level. Four of the pts were female, the median age was 65 years (48- 74), 11 had a performance status of 0–1, and only 1 pt received prior chemotherapy. There were no IDLTs at the first dose level, and there was one IDLT of infection with neutropenia at the second dose level. The median number of cycles completed was 5 (range 1–12 cycles). Aside from grade 3 fatigue in 2 pts there were no grade 3 or greater non-hematologic toxicities. Common non-hematologic toxicities included peripheral neuropathy, constipation, fatigue, and alopecia. Of the 12 pts, the best response was stable disease in 9 pts, 2 are without disease progression, and 6 pts are alive to date. The median progression free survival was 3.3 months (range 0.7–10.7 months). Conclusions: The combination of paclitaxel poliglumex and pemetrexed was well tolerated at the proposed phase II dose of 175 mg/m2 and 500 mg/m2. The PFS is encouraging and future studies of this combination are recommended. No significant financial relationships to disclose.
Gefitinib plus concomitant boost accelerated radiation (AFX-CB) and concurrent weekly cisplatin for locally advanced unresectable squamous cell head and neck carcinomas (SCCHN): A phase II study
Authors: A. Rueda, J. A. Medina, R. Mesía, R. Galiana, M. E. Vega, A. Collado, M. Cobo, J. Contreras, M. Marguelí, E. Alba
Journal: Journal of Clinical Oncology (2007)

6031 Background: Molecular inhibition of EGFR signaling represents one of the most promising current advances for the treatment of SCCHN. This study assesses the feasibility, toxicity and efficacy of gefitinib along with AFX-CB regimen and weekly cisplatin in treatment- naïve patients (pts) with locally advanced unresectable SCCHN. Methods: Eligible pts had stage III-IV SCCHN, exclusive of nasopharyngeal cancer. Tumors had to be considered unresectable by a multidisciplinary head/neck tumor board. AFX-CB dose was 72 Gy in 42 fractions over 6 weeks, delivered in 1 daily fraction of 1.8 Gy during the first 3.5 weeks and 2 fractions per day, 1.8 Gy and 1.5 Gy separated by a 6-hour interval, during the last 2.5 weeks. Cisplatin (40 mg/m 2 ) was given weekly for the first 4 weeks. Gefitinib (250 mg PO OD) was started 1 day before radiochemotherapy (RCT) and continued 3 months after the end of AFX-CB. Response was evaluated 3 months after radiotherapy using RECIST criteria. Mucosal and skin toxicities were evaluated using the RTOG scale. Results: From Dec 2002 to Dec 2004, 46 pts with SCCHN, ECOG PS 0–1 and adequate hematologic and renal functions were included. Median age was 55 years (range, 39 to 75); T4, 73%; N2/3, 61%; stage IV disease, 93%. Four pts did not complete the concomitant treatment (1 PD/3 toxicity) and 8 pts did not complete the gefitinib monotherapy phase due to PD. Grade 3 and 4 toxicity was consistent with previous RCT or single agent gefitinib trials, and included mucositis (40% and 7%, respectively), radiation dermatitis (14% and 0%), skin rash (5% and 0%), and diarrhea (2% and 0%). Chemotherapy-associated toxicity was mild with only 2 cases of grade 3 neutropenia and 3 cases of grade 3 anaemia. Three months after AFX- CB, 24 pts (52%) achieved a complete remission, 5 pts (11%) a partial remission, and 17 pts (37%) were non-responders (SD, PD, and not evaluable). With a median follow-up of 23 months (range 1–43) 2-year PFS and OS are 47% and 56% respectively. Conclusions: The addition of gefitinib to radiochemotherapy appears tolerable and feasible. Efficacy is encouraging for this poor prognosis population, and further development of this targeted combined-modality paradigm is warranted. No significant financial relationships to disclose.
Canadian oncologist communication about prognosis disclosure with their terminally-ill patients
Authors: G. A. Harding, F. J. Hlubocky, M. Siegler, C. K. Daugherty
Journal: Journal of Clinical Oncology (2008)

6554 Background: Prior research indicates that oncologists are reluctant to discuss prognosis (prog) with their terminally-ill cancer patients (tcp), yet physician attitudes have not been well described. Methods: We surveyed Canadian medical oncologists' (mo) self-reported behaviors, beliefs and attitudes regarding prog communication (comm) with their tcp. Following a pre-notification letter, surveys were mailed to a systematic sample of 335 mo with Canadian addresses listed in the 2005 ASCO and RCPSC Members Directory. Results: Surveys were mailed with a $5 cash incentive in April, 2006. 196 surveys were completed and returned (59% response rate). Median age of respondents (res) is 44 (29–73); 66% men; 54% at university affliated institution. Res have practiced a median 11 years (1- 43) and see a median 45 (6–300) patients/week. Answering yes or no, 99% of res say their usual practice is to tell their tcp they will eventually die of their disease. Choosing from closed-ended responses: 34% say they always discuss prog, 50% discuss prog only after asking their tcp if they want the information, and 16% discuss it only if their tcp ask for the information. 34% say they always or usually communicate a timeframe as to when death may occur and 50% sometimes, rarely, or never give a timeframe. If they do not tell a tcp their prog, 19% always, 22% usually, 28% sometimes, and 24% rarely or never tell family or friends. 92% are always or usually satisfied with their prog comm. 92% say their tcp are always or usually satisfied with the comm. 96% believe prog comm education should be part of cancer-care training. 40% say such education was either absent or inadequate during their training. Older mo(<45y) were less likely to report always/usually telling their tcp timeframe re prog (OR=0.69; p=0.02) as were those who did not receive training (OR=0.35; p<0.00). Qualitative data has also been collected about: clinical factors affecting mo prog comm, associated emotions, and examples of recent prog comm. Conclusions: Almost all Canadian mo report that they tell their tcp that they have a known life-ending prog. When they do not tell their tcp they frequently tell family or friends. Most Canadian mo say they provide a prognostic timeframe to their tcp re: time left to live. No significant financial relationships to disclose.