tbuckley/cabot-search huggingface dataset:
Patient-reported toxicity after treatment for cancers of the head and neck.
Authors: Christine E. Hill-Kayser, Carolyn Vachani, Margaret K. Hampshire, Gloria A. Di Lullo, James M. Metz
Journal: Journal of Clinical Oncology (2012)

6135 Background: Patients with cancers of the head and neck (HNC) may be at risk for significant late effects after treatment. Quality of life may be altered significantly as a result. This Internet based study evaluates patient perceptions of toxicity after treatment for HNC. Methods: Patient-reported data were gathered via a convenience sample frame from HNC survivors voluntarily utilizing a publically available, free, Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and through the OncoLinkwebsite, the tool allows survivors to enter data regarding diagnosis, demographics, and treatments, and provides customized guidelines for future care. During use of the tool, HNC survivors are queried regarding late effects associated with specific treatments. All data have been maintained with IRB approval. Results: Of 3866 survivors using this tool between 4/2010 and 10/2011, 140 (4%) had undergone primary treatment for HNC. Median diagnosis age was 52y and median current age 56y. When queried regarding treatment received, 88% reported having undergone radiation, 73% surgery, and 67% chemotherapy. Many patient-reported late effects were associated with local tumor control, and included difficulty swallowing/speaking (83%), decreased saliva production (88%), dental problems (49%), thyroid problems (33%), decreased neck mobility (60%), eye and vision deficits (9%), and tinnitus (40%). In addition, 53% noted concerns regarding cognitive function. Users of the tool reported that they would share it with their healthcare team in 55% of cases. The most common reasons for not sharing it were “I did not think they would care,” and “ I did not want to upset or anger them.” Conclusions: Survivors using this tool anonymously and voluntarily report significant toxicity after treatment for HNC. Not all survivors appear comfortable discussing these issues with healthcare providers, despite major potential impact on quality of life. The data reported here may be of significant impact in future study of outcomes after HNC, as well as patient counseling and survivor care.
Phase I study of cabazitaxel (Cbz) plus cisplatin (Cis) in patients (pts) with advanced solid tumors: Substudy to evaluate the impact of a strong CYP3A inhibitor (ketoconazole; K) or inducer (rifampicin; R) on the pharmacokinetics (PK) of Cbz.
Authors: Alain C. Mita, Albert C. Lockhart, James Lloyd Wade, John Charles Morris, Olivier Rixe, Jean-François Dedieu, Claudine Wack, Laurent Kassalow, John Sarantopoulos
Journal: Journal of Clinical Oncology (2013)

2560 Background: Cbz is approved for treatment of pts with hormone-refractory metastatic prostate cancer after progression on a docetaxel-containing regimen. The dose-escalation part of this Phase I study (NCT00925743) found the maximum tolerated dose (MTD) of Cbz/Cis to be 15/75 mg/m 2 . No Cbz–Cis PK interactions were seen. As Cbz is mainly metabolized by CYP3A, the study also evaluated the impact of a strong CYP3A inhibitor (K; study part 3) or strong CYP3A inducer (R; study part 4) on the PK of Cbz in combination with Cis. Methods: The study included pts with metastatic or unresectable solid tumors for which Cis-based therapy was considered appropriate. Pts received Cbz/Cis every 3 weeks at MTD, with K 400 mg (part 3) or R 600 mg (part 4) administered orally once daily prior to, on, and after Cycle 2 Day 1 for a total of 10 (K) or 14 (R) days. In part 3, the Cbz/Cis dose was 5/75 mg/m 2 in Cycles 1 and 2 to provide a safety margin to the MTD. Effects on Cbz PK were assessed with a linear mixed-effects model. The primary endpoint was Cbz clearance (CL). Safety assessments included adverse events (AEs) and laboratory abnormalities. Results: The PK population included 23 pts (part 3) and 21 pts (part 4). Repeated administration of K resulted in a 20% decrease in Cbz CL (L/h/m 2 ) (geometric mean ratio [GMR]: 0.80; 90% confidence interval [CI]: 0.55, 1.15; n = 18), corresponding to a 25% increase in AUC (ng*h/mL/mg/m 2 ) (GMR: 1.25; 90% CI: 0.86, 1.81; n = 18). Repeated administration of R resulted in a 21% increase in Cbz CL (L/h/m 2 ) (GMR: 1.21; 90% CI: 0.95, 1.53; n = 20), corresponding to a 17% decrease in AUC (ng*h/mL/mg/m 2 ) (GMR: 0.83; 90% CI: 0.65, 1.05; n = 20). The GMR of AUC 0–24 was 1.09 (90% CI: 0.9, 1.33; n = 21), suggesting a low impact of R during the initial phases of Cbz elimination. The most frequent AEs included nausea (part 3: 68%; part 4: 74%), vomiting (part 3: 68%; part 4: 74%) and fatigue (part 3: 52%; part 4: 70%). Conclusions: The CL of Cbz was decreased by 20% by co-administration with K and increased by 21% by co-administration with R. Safety results were consistent with prior findings for this Cbz/Cis combination. Clinical trial information: NCT00925743.
Pharmacokinetics, safety, and tolerability of a new patritumab formulation in patients with advanced, refractory solid tumors.
Authors: Kyriakos P. Papadopoulos, Kathleen N. Moore, Richard Lush, Madhuri Desai, Syed Mahmood, Robert A. Beckman, Jeanne Mendell-Harary
Journal: Journal of Clinical Oncology (2015)

e14026 Background: Patritumab, currently in phase 3 study for non–small cell lung cancer, is a fully human monoclonal antibody directed against human epidermal growth factor receptor 3 (HER3). To support a new manufacturing process, an open-label bridging study was conducted to assess pharmacokinetics (PKs), safety, and tolerability of the new formulation (Process 2 patritumab [P2P]), relative to the original (Process 1 patritumab [P1P]), in patients (pts) with advanced cancer. Methods: Pts with known HER3+ tumor types, Eastern Cooperative Oncology Group performance status ≤ 2, and refractory to/refused standard treatment were eligible. P2P was administered on day 1 at a loading dose of 18 mg/kg (cycle 1), then maintenance with 9 mg/kg (cycles 2–5) every 21 days. PK was assessed following single-dose (18 mg/kg) P2P. Data assessed include area under the curve from day 0 to 21 (AUC0–21) and maximum concentration (Cmax; primary end points), treatment-emergent adverse events (TEAEs), serious AEs (SAEs), anti–patritumab neutralizing antibodies (HAHA), and tumor response. PK was compared with historical P1P PK (18 mg/kg) data. Results: Seventeen pts completed ≥ 1 cycle, and 9 pts completed all 5 cycles. P2P exposure was 128.6% (AUC0–21; 90% confidence interval [CI]: 112.5%–146.9%) and 134.0% (Cmax; 90% CI: 119.7%–149.9%) compared with P1P. TEAEs (mostly grade ≤ 2) were reported in 15 of 17 (88.2%) pts; TEAEs in 33.5% of pts were considered related to P2P. One grade 4 TEAE (hypophosphatemia) was reported. The most frequently ( > 25% of pts) reported TEAEs were gastrointestinal. Of the 6 SAEs in 5 pts, 2 (nail infection; orthostatic hypotension) were considered related to P2P. One grade 3 SAE (intestinal obstruction; resolved) led to P2P interruption. No pt discontinued due to TEAEs or SAEs. No pt developed HAHA. Two pts (cervical cancer; pancreatic cancer) demonstrated a partial response; 12 had a best overall response of stable disease. Conclusions: P2P was well tolerated with no HAHA formation and with similar bioavailability to the P1P. P2P will be used in the pivotal study. Clinical trial information: NCT01957280.
Prostate cancer stage at diagnosis: First data from a Middle-Eastern cohort.
Authors: Deborah Mukherji, Sarah Abed El Massih, Marilyne Daher, Alissar Chediak, Maya Charafeddine, Mohammed Shahait, Sally Naji Temraz, Fady B. Geara, Albert El Hajj, Rami Nasr, Wassim Wazzan, Mohammad Bulbul, Raja Khauli, Ali Shamseddine
Journal: Journal of Clinical Oncology (2017)

e552 Background: Current data suggest that prostate cancer incidence is increasing in the Middle East and North Africa (MENA) region however remains significantly lower than the United States and Europe. No data are available regarding stage at diagnosis or treatment. SEER data from the US suggest that only 4% of patients present with metastatic disease. We hypothesized that rates of presentation with stage 4 disease are significantly higher in the MENA region. Methods: After IRB approval, a review of prostate cancer cases presenting to the leading tertiary referral center in Lebanon from January 2010 to July 2015 was undertaken. From September 2014 these data were collected prospectively. The American University of Beirut Medical Center sees approximately one third of all cancer cases in the country and is a major referral center for Syria and Iraq. Results: 582 cases were identified, median age at diagnosis was 68 (range 43-97); median PSA at diagnosis was 10.2ng/ml (range 2.3 – 3490), median Gleason score was 7. 480 patients had staging data available; 77.4% (449) presented with organ-confined disease, 22.6% (136) presented with stage 4 disease at diagnosis. 12% of this cohort were from Iraq, 57.6% presenting with stage 4 disease. Increasing age correlated with higher stage at presentation in this cohort. In patients presenting with PSA &gt; 20, 62.3% were found to have stage 4 disease. Conclusions: This is the first report of prostate cancer stage at diagnosis from a large cohort of patients from the Middle East showing a median age at diagnosis of 68 and 22.6% presenting with stage 4 disease. These data highlight the importance of multi-disciplinary management and health-care system planning for the rising burden of prostate cancer affecting the MENA population.
A phase I dose-defining study for MK-2206 combined with gefitinib in NSCLC population enriched with EGFR mutation.
Authors: Chia-Chi Lin, Chong-Jen Yu, Chao-Chi Ho, Kuan-Yu Chen, Jin-Yuan Shih, Zhong-Zhe Lin, Yu-lin Lin, Wei-Yu Liao, Shoung-Hui Tsai, Li Yan, James Chih-Hsin Yang
Journal: Journal of Clinical Oncology (2014)

e19013 Background: The PI3K/AKT pathway is one of the key pathways of EGFR signaling in NSCLC. We hypothesize that combination of gefitinib with MK-2206, an allosteric oral AKT inhibitor, will overcome the development of EGFR TKI resistance and further increase the therapeutic efficacy of gefitinib. Preclinical data support the synergistic effect of this combination. The purpose of this study is to define the MTD of MK-2206 when combined with gefitinib in NSCLC. Methods: The main eligibility criteria include metastatic NSCLC patients who previously failed and progressed through more than 3 months’ use of EGFR TKI (e.g. erlotinib, gefitinib, afatinib) and ³1 line of chemotherapy. Cohorts of 3+3 patients will be enrolled on escalating doses (level -1, 90 mg; level 1, 135 mg; level 2 200 mg QW) of MK-2206 followed by gefitinib (250 mg QD). DLT is Gr 4 ANC ≥7 d, Gr 3 febrile neutropenia, Gr 4 PLT; Gr ≥3 non-hemat toxicity except inadequately treated vomiting, diarrhea, asymptomatic hyperglycemia without Gr ≥3 electrolytes (but AC ≤250, PC ≤500 mg/dL), hypersensitivity, ALT ≤1 wk; and toxicity leading to a dose modification or causing a ≥3 wk delay. Results: A total of 14 patients (median age 62, range 35 - 84; median prior treatments 4, range 2 - 6) who had been treated with gefitinib (n = 4), erlotinib (alone or with afatinib; n = 7), or both (n = 2) were enrolled, starting at MK-2206 QW 135 mg (n = 3) with 1 DLT (grade 3 vomiting). MK-2206 was de-escalated to 90 mg (n = 3) without DLT. MK-2206 was then escalated to 135 mg (n = 5) with 1 DLT (grade 2 erythema multiforme, which recovered upon 6-day cessation of MK-2206 and recurred after MK-2206 dose reduction to 90mg). No DLTs were observed at 200 mg (n = 3) QW. The most common toxicities of all grades for the combination of gefitinib and MK-2206 were eosinophil increase (n = 9), rash (n =9), diarrhea (n = 7), hyperglycemia (n = 4), and mucositis (n = 4). The recommended phase II dose identified was gefitinib 250 mg QD and MK-2206 200 mg QW. Two pts with MK-2206 200 mg QW had minor responses (-18, -20%) with symptomatic improvement for 8 and 27 wks, respectively. Conclusions: Gefitinib combined with MK-2206 is well tolerated and had shown preliminary activity in NSCLC patients with acquired resistance to EGFR TKIs. Clinical trial information: NCT01147211.
Validation of a 17-Gene Genomic Prostate Score (GPS) as a predictor of biochemical recurrence (BCR) in men with prostate cancer treated with radical prostatectomy (RP) in a community setting.
Authors: Stephen K. VanDenEeden, Nan Zhang, Charles P Quesenberry, Jeong S Han, Amethyst D Leimpeter, Jun Shan, Athanasios C. Tsiatis, H. Jeffrey Lawrence, Phillip G. Febbo, Joseph C Presti
Journal: Journal of Clinical Oncology (2017)

41 Background: Validated biomarkers can improve risk stratification for men with prostate cancer (PCa). A biopsy-based RT-PCR assay that provides a GPS (scale 0-100) has been validated as an independent predictor of adverse surgical pathology and BCR after RP in men with low-risk and low-volume intermediate-risk PCa. We sought to confirm that GPS is a predictor of BCR across the full spectrum of clinical risk (low, intermediate and high) in a large cohort of men with long term follow up within Kaiser Permanente Northern California (KPNC). Methods: From the KPNC clinical database of 6,184 RP treated men diagnosed with NCCN very low, low, intermediate and high-risk PCa between 1995- 2010, we performed a retrospective cohort study using stratified cohort sampling. BCR was defined as either 2 successive post-RP PSAs ≥ 0.2, or initiation of salvage therapy after a rising PSA ≥ 0.1. Archival biopsy tissue was assayed to yield a GPS. Univariable and multivariable Cox proportional hazards models were used to estimate the association, accounting for sampling weights and covariates. Results: Tissue was retrieved for 334 patients. 279 met all eligibility criteria and 259 (93%) generated a valid GPS. The cohort consisted of 117 BCR and 142 non-BCR events. GPS was strongly associated with BCR - HR/20 GPS units = 2.5; p &lt; 0.0001 in univariable analysis, and after adjusting for PSA, clinical T stage and central biopsy Gleason Score (HR/20 units = 2.1; p = 0.002). The association between GPS and BCR was similar within different racial groups. Each of the 4 gene groups in GPS contributed to the prediction of BCR. Conclusions: GPS was associated with BCR independently of other clinical factors in surgically treated men with PCa, and may provide improved risk stratification beyond clinical risk assessment.
Impact of castration resistant status on overall survival for prostate cancer patients treated with radical prostatectomy.
Authors: Naoki Fujita, Takuya Koie, Hayato Yamamoto, Atsushi Imai, Yuki Tobisawa, Tohru Yoneyama, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Chikara Ohyama
Journal: Journal of Clinical Oncology (2017)

e562 Background: We estimated the natural history and predictive factors of oncological outcomes in patients with prostate cancer (PCa) after radical prostatectomy (RP). Methods: In this retrospective study, we reviewed the clinical and pathological records of 1083 PCa patients who underwent RP and bilateral pelvic lymphadenectomy with or without neoadjuvant therapy between July 1996 and December 2014 at Hirosaki University. All patients were followed-up by assessing serum prostate-specific antigen (PSA) and testosterone levels every 3 months for 5 years and every 6 months thereafter. The endpoint was the oncological outcomes after surgery. Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model. Results: The 5-year and 10-year overall survival rates were 98.5 % and 92.0 %, respectively. At the end of the study, 226 patients (20.8%) showed biochemical recurrence and 28 patients (2.6%) had developed castration-resistant Pca (CRPC). The patients with CRPC were significantly poor prognosis compared with those without CRPC (P &lt; 0.01). On multivariate analysis, although preoperative variables were no significant differences, only CRPC was significantly associated with OS. Conclusions: RP was shown to provide excellent long-term survival with OS at 10 years. In addition, a small proportion of the patients treated with RP had CRPC and died of Pca within 10 years. Development to castration resistant status may have critical impact on OS.
Oncogenic role of miR-483-3p at the IGF2/483 locus (Cancer Research (2010) 70, (3140-3149) DOI: 10.1158/0008-5472.CAN-09-4456)
Authors: A. Veronese, L. Lupini, J. Consiglio, R. Visone, M. Ferracin, F. Fornari, N. Zanesi, H. Alder, G. D'Elia, L. Gramantieri, L. Bolondi, G. Lanza, P. Querzoli, A. Angioni, C. M. Croce, M. Negrini
Journal: Cancer Research (2010)
Geographic Differences in Phenotype and Treatment of Children with Sickle Cell Anemia from the Multinational DOVE Study
Authors: Baba Inusa, Raffaella Colombatti, David C Rees, Matthew M Heeney, Carolyn C Hoppe, Bernhards Ogutu, Hoda M Hassab, Chunmei Zhou, Suqin Yao, Patricia B Brown, Lori E Heath, Joseph A. Jakubowski, Miguel R Abboud
Journal: Blood (2016)
Genetic Determinants of Diabetic Nephropathy
Journal: Journal of the American Society of Nephrology (2003)

Diabetes mellitus is the leading cause of ESRD in the United States. Family-based studies and segregation analyses suggest that inherited factors play a major role in susceptibility to diabetic renal complications, including albuminuria and chronic kidney failure. The Family Investigation of Nephropathy and Diabetes (FIND) study is a multicenter consortium established by the National Institute of Diabetes, Digestive and Kidney Diseases to identify the gene(s) responsible for diabetic nephropathy. Eight participating centers will enroll nearly 10,000 individuals by September 2004. Two independent strategies to detect causative genes will be used. These include family-based linkage analyses in African-American, American-Indian, Mexican-American, and European-American families (predominantly affected and discordant relative pair analyses) and mapping by admixture linkage disequilibrium (MALD) in African and Mexican Americans. Cell lines are being created from participants, and a repository containing stored urine and serum samples has been developed. This paper describes the enrollment criteria and methods used in FIND to allow for the detection of gene(s) predisposing to diabetic nephropathy.
Pazopanib versus paclitaxel in relapsed urothelial tumors: A randomized phase II study investigating pazopanib versus weekly paclitaxel in relapsed or progressive transitional cell carcinoma of the urothelium (PLUTO).
Authors: Robert J. Jones, John D. Chester, Judith Dixon-Hughes, Laura Alexander, Amit Bahl, Syed A. Hussain, Alison Birtle, Satinder Jagdev, Anna Morris, Jamie Stobo, Caroline A Bray, James Paul, Tom Powles
Journal: Journal of Clinical Oncology (2014)

TPS4589 Background: Urothelial cancer (UC) is a chemosensitive disease. There is a clear role for first line, platinum-based chemotherapy in advanced disease, response rates being around 40-50%. However, responses are usually brief and the role of subsequent therapy remains unclear. There are currently no approved second line therapies in North America, although vinflunine is approved in some countries. Nevertheless, a variety of second line therapies are widely used on the basis of modest response rates observed in small, non-randomized phase II trials. In the UK, the most commonly used second line therapy is paclitaxel. Two non-randomized phase II trials with the vascular endothelial growth factor (VEGF) receptor targeted tyrosine kinase inhibitor pazopanib suggest clinical activity in this setting. Methods: 140 patients with progressive advanced UC who have failed a single prior line of chemotherapy which must have contained platinum will be randomized to receive either pazopanib 800mg once daily until progression or paclitaxel 80mg/m2 days 1, 8, 15 of a 28 day cycle for up to 24 weeks. The primary endpoint of the study is overall survival. Secondary endpoints include progression free survival, response rate, safety and tolerability. Archival tissue, blood and urine samples will be collected prospectively from patients, in order to explore molecular and genomic predictors of benefit for both drugs. The trial is designed to detect a 50% improvement in overall survival (paclitaxel 8 months; pazopanib 12 months) with power 90% and 1-sided significance level of 20%. If positive, a randomized phase III trial will be required to confirm efficacy of pazopanib in this population. On 1 Feb 2014, 70 patients had been recruited. Clinical trial information: 73030316.
Biomarker study in patients with resectable AJCC stage IIIc or stage IV (M1a) melanoma treated in a randomized phase II neoadjuvant trial.
Authors: Nitin Chakravarti, Doina Ivan, Merrick I. Ross, Joseph L. Ilagan, Carla L. Warneke, Kevin Kim, Nicholas E. Papadopoulos, Suzanne Cain, Jeffrey E. Gershenwald, Marcella M. Johnson, Agop Y. Bedikian, Richard E. Royal, Janice N. Cormier, Ehab Y. Hanna, Jeffrey Edwin Lee, Victor G. Prieto, Wen-Jen Hwu
Journal: Journal of Clinical Oncology (2013)

9047 Background: Fewer than 30% of patients with resectable stage IIIC or IV (M1a) metastatic melanoma (MetM) who undergo surgical resection will achieve long-term survival. This study was designed to administer neoadjuvant systemic therapy prior to definitive surgery to explore potential predictive and prognostic biomarkers in patients with MetM. Methods: Fifty patients with resectable MetM were randomized to receive temozolomide (TMZ) alone at 150 mg/m 2 /day x 7 days every other week (Arm A, n=26) or with pegylated interferon (PGI) at 0.5 mcg/kg weekly (Arm B, n=24). After a pre-treatment tumor biopsy, patients received 8 weeks of neoadjuvant therapy before undergoing surgery. Endpoints were clinical response, tolerability, and biomarker analysis by immunohistochemistry and gene array. In particular, we examined PD-1, PD-L1, pAKT, pMAPK, Ki67, and caspase 3. Patients with response (complete-, partial-, or stable disease) received up to 3 additional cycles of the assigned regimen as adjuvant therapy. Results: Overall response to neoadjuvant therapy was 38% [1 CR, 15 PRs, 3 SDs]: 31% in Arm A (95% CI 14% - 52%) and 46% in Arm B (95% CI 26% - 67%). Estimated 4-year overall survival was 52.52% (95% CI 35.86 - 66.74%). Only 5 patients did not undergo definitive surgery after neoadjuvant treatment due to development of distant metastasis. Preliminary data indicate that in Arm B, responders had higher PD-1 membranous expression in tumor infiltrating lymphocytes (TILs) (p=0.029). Furthermore, low PD-L1 cytoplasmic expression in TILs (p=0.002) as well as low nuclear PD-L1 expression in tumor cells (p=0.025) had better overall survival. Conclusions: Comparing with historical data, neoadjuvant therapy has a potential to improve overall survival in patients with resectable MetM. Biomarker analysis may predict response to neoadjuvant treatment as well as overall survival. Clinical trial information: NCT00525031.