tbuckley/cabot-search huggingface dataset:
Real-world corticosteroid utilization in prostate cancer patients treated with two new oral agents.
Authors: Marie-Helene Lafeuille, Amanda M. Grittner, Patrick Lefebvre, Lorie Ellis, R. Scott McKenzie
Journal: Journal of Clinical Oncology (2014)

265 Background: Two oral agents have recently been approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC): abiraterone acetate (AA) combined with prednisone (P) for treatment of patients with mCRPC and enzalutamide (ENZ) for patients with mCRPC previously treated with docetaxel. Although corticosteroid (CS) co-administration is not required in ENZ prescribing information, 48% of ENZ-treated patients receive CS according to a large phase III clinical trial. To date, real world CS utilization patterns in AA- and ENZ-treated patients has not been reported. Methods: ProMetis Lx administrative claims data covering multiple health plans were used to identify patients with ≥1 PC diagnosis (ICD-9 185, V10.46) during ≥6 months of claims activity before the first AA or ENZ claim (index date). The proportion of patients receiving CS (identified by NDC codes) during AA or ENZ treatment (observation period-defined as first to end of last AA or ENZ prescription) was reported using descriptive statistics. Additionally, dosing and medication possession ratio (MPR) were calculated for the subset of patients receiving P. Results: A total of 3,228 AA-treated and 675 ENZ-treated PC patients were identified. Baseline comorbidities patterns were similar between treatment groups for hypertension (AA 55%, ENZ 56%), diabetes (25% both groups), and cardiovascular disease (28% both groups). The mean (SD) observation period for AA-treated patients was 142 (133) days and for ENZ-treated patients was 74 (46) days. CS use, P dose and P MPR are described in the following table. Conclusions: CS use was common in PC patients prior to and during treatment with AA and ENZ. While this data set may underreport CS use, patterns of CS use are consistent with clinical trial data. Further research based on data with longer follow-up and additional observational datasets is warranted. [Table: see text]
Fractionated dose radiolabeled antiprostate specific membrane antigen (PSMA) radioimmunotherapy (<sup>177</sup>Lu-J591) with or without docetaxel for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Jaspreet S Batra, Beerinder S Karir, Shankar Vallabhajosula, Paul J. Christos, Gillian Hodes, Pravin R. Date, Anastasia Nikolopoulou, Yuliya Jhanwar, Himisha Beltran, David M. Nanus, Stanley J. Goldsmith, Neil Harrison Bander, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2015)

194 Background: A phase II trial single-dose 177 Lu-J591 was published. Dose fractionation offers theoretic advantages and 2 phase I dose-escalation studies of 177 Lu-J591 have been performed to test the hypothesis that higher cumulative radiation doses can be administered with an acceptable toxicity profile. Methods: Pts with mCRPC and normal neutrophil and platelet counts were enrolled in 2 sequential phase I dose-escalation studies: (1) 177 Lu-J591 administered as a single-agent 2 doses 2-weeks apart to determine the maximum tolerated dose (MTD) with expansion cohorts at the recommend phase II doses (RP2D) and (2) fractionated dose 177 Lu-J591 in combination with docetaxel 75 mg/m 2 q3 weeks to determine the MTD. Results: 44 men with median age 75.4 (range 55.1-95.2) were enrolled in the single-agent fractionated dose escalation 177 Lu-J591 trial and 15 men with median age 69.1 (49.3-80.8) were enrolled in 177 Lu-J591 + docetaxel trial. The RP2D’s of fractionated 177 Lu-J591 were 40 mCi/m 2 x2 or 45 mCi/m 2 x2 with the option for GCSF; at these doses (n=28), 8 (28.6%) with &gt;50%, 11 (39.3%) &gt;30%, and 16 (57%) of 28 pts with any PSA decline; pts at RP2D lived longer (p&lt;0.0001). Predictable, reversible myelosuppression was seen. 18 (40.9%) received chemo prior to RIT and 24 (54.5%) received chemo post 177 Lu-J591 [median of 7 cycles (range 1-20)]. In combination with docetaxel, the MTD/RP2D of 177 Lu-J591 is 40 mCi/m 2 x2 doses (delivered with cycle 3), with 73.3% &gt;50%, 80.0% &gt;30%, and 86.7% with any PSA decline. Conclusions: Fractionated 177 Lu-J591 is tolerated with subsequent PSA declines and reversible myelosuppression. The apparent dose-response of single-dose 177 Lu-J591 appears confirmed with fractionated dosing (improved PSA declines and OS at higher doses). Despite predictable myelosuppression, chemotherapy is able to be delivered prior to 177 Lu-J591, concurrently, or following radioimmuotherapy. Clinical trial information: NCT00538668 , NCT00916123 .[Table: see text]
Changes in profession and patient-physician relationship in doctors with a personal experience of cancer
Authors: A. Ricciuti, A. Burrone, F. Della Beffa, S. Gastaldi, R. Labianca, M. Lazzari, M. Provantini, C. Verusio, S. Villa
Journal: Journal of Clinical Oncology (2008)

17504 Background: An exploratory analysis was performed to investigate if physicians with cancer modify their relationship with the profession and with the patients. Methods: The modifications have been surveyed through an ad hoc questionnaire (Q). Q (107 items) covered personal data, involvement in cancer diagnosis and therapy definition, changes in personal and professional life including 2 questions about the perceived overall modification (“the cancer changed the way I work” and “my relationship with the patients has changed”) and 24 specific items (eg “time devoted to study has changed” and “I agree more easily with support or nonconventional therapies”). Through the support of the AIOM, Q was distributed to all 205 associated head oncologists, to be further distributed to the cancer affected doctors. Betweeen 12/2006 and 3/2007, 103 self completed Qs have been collected, with no selection by gender, age, type of cancer. 12 Qs were excluded from the analysis because of missing data. The data underwent descriptive statistical analysis; the association among the declared modification were analyzed through the chi-square test. Results: An overall modification in the profession were reported by 24% of the subjects, but 17% more declared at least 2 specific changes. An overall modification with the patients were reported by 32% of the subjects, but 25% more declared at least 4 changed atittudes; 47% declared 4 or more increased items in the relational-emphatic area. The modification in the profession and with the patients are strongly associated between themselves (chi-square p 0.001) and with the reported general changes (chi- square p<0.01). Conclusions: After cancer 41% and 57% of the physicians report modification in the profession and with the patients respectively, but a minor percentage declare an overall change. Most of the modifications show increased attention and personal availability, addressed both to patients and to themselves. These results should be confirmed by a larger sample and possibly by the identification of a control group. No significant financial relationships to disclose.
Disease Risk Index Is the Major Predictor of Outcome Following Myeloablative Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HSCT) and Post-Transplant Cyclophosphamide (PT/Cy)
Authors: Scott R. Solomon, Connie Sizemore, Xu Zhang, Melhem Solh, Lawrence E. Morris, H. Kent Holland, Asad Bashey
Journal: Blood (2015)
Unexpected Monoclonal T Cell Line Derived From the Bone Marrow of a Multiple Myeloma Patient.
Authors: Debora Levy, Graciela Aparecida Brocardo, Carla Rosa Teixeira de Godoy, Camila da Cruz Gouveia Linardi, Jorge Maria Ruiz, Gracia Martinez, Adilson Ferreira Kleber, Durvanei Augusto Maria, Juliana Pereira, Sergio Paulo Bydlowski
Journal: Blood (2009)
Preliminary data from an ongoing phase IIb study of no carrier added <sup>131</sup>I-iobenguane (nca-MIBG) in patients with malignant pheochromocytoma (Pheo).
Authors: D. A. Pryma, J. A. Barrett, R. E. Coleman, R. Noto, C. Jimenez, M. H. Pampaloni, A. N. Serafini, R. L. Wahl, L. Kostakoglu, N. D. LaFrance, J. W. Babich
Journal: Journal of Clinical Oncology (2011)

e21122 Background: 131I-iobenguane, a substrate for the norepinephrine transporter, specifically localizes in Pheo. Iobenguane competitively inhibits catecholamine reuptake, causing cardiovascular side effects. Cardiovascular toxicity is a major concern in the use of targeted agents in the treatment of Pheo given the pathologic catecholamine expression. We initiated a study of no-carrier added 131I-nca-MIBG to treat patients with the lowest possible mass of iobenguane. Aims of this ongoing study in metastatic Pheo patients (pts) were: to determine the efficacy of no-carrier added 131I-nca-MIBG to provide clinical benefit, as defined by reduction in antihypertensive therapy; overall tumor and biomarker response; and safety. Methods: Pts with metastatic Pheo and taking antihypertensive medication were treated with up to two 500 mCi doses of 131I-nca-MIBG 3-6 months apart. The administered dose was limited by gamma image-derived pretreatment organ dosimetry and normal tissue tolerance estimates of Emami (1991), if needed. Tumor response and toxicity were evaluated for a minimum of 1 year. Results: To date, 41 pts (17-72 years) received at least one treatment; 10 pts received 2 treatments have completed > 9 month follow-up. RECIST measurements of CT/MRI scans showed partial response, mixed response, or stable disease in 5, 2, and 3 pts, respectively. Serum chromogranin A levels trended with reduction in tumor size (mean change -73 and -69% at 6 and 12 months post-treatment, respectively, range -36 to -97% and -18 to -96%, respectively). Beneficial effect on hypertension as measured by a reduction in all antihypertensive medication by at least 50% for at least 6 months was achieved in 7/10 pts evaluated. Primary toxicity in the 41 pts was, as anticipated, myelosuppression including Grade 3 (17%) and Grade 4 (20%). Grade 3 GI disorders were 15%. There were 3 deaths due to disease progression. Conclusions: In 10 pts with > 9 mo observation in this ongoing study a positive clinical benefit was obtained which correlated with overall tumor response as measured by RECIST and biomarker levels. Toxicity for all patients (n=41) was tolerable and predominantly limited to myelosupression.
A phase I dose escalation study of irinotecan (CPT-11), oxaliplatin (Oxal), and capecitabine (Cap) within three UGT1A1 TA promoter cohorts (6/6, 6/7, and 7/7)
Authors: M. P. Goetz, S. Safgren, R. M. Goldberg, A. F. Grothey, S. J. Mandrekar, J. M. Reid, C. Erlichman, A. A. Adjei, J. Rubin, M. M. Ames
Journal: Journal of Clinical Oncology (2005)

2014 Background: Patients (pts) with the UGT1A1 *28 genotype have a higher risk of CPT-11 induced diarrhea and neutropenia, but no validated guidelines exist for use of UGT1A1 genotype to dose patients receiving CPT-11. We designed a phase I study to develop UGT1A1 genotype specific dosing of CPT-11, Oxal, and Cap in pts with advanced solid tumors. Methods: Potentially eligible pts underwent UGT1A1 *28 genotyping (GeneScan) and were stratified into one of 3 cohorts: 7/7, 6/7, or 6/6. Initially, only 7/7 and 6/7 pts were eligible and enrolled at dose level 1. After DLT was seen for 6/7 pts, the trial was opened to 6/6 pts at dose level 2. Pts received CPT-11 and Oxal day 1, and Cap days 2 - 15 every 3 weeks. The following cycle 1 toxicities were defined as DLT: grade (G) 4 ANC >5 days, G4 hemoglobin or platelet, creatinine ≥2 x baseline, treatment delay > 14 days, sensory neuropathy ≥ G3, and any non-hematologic toxicity ≥ G3. Results: 35 pts underwent UGT1A1*28 genotyping: 6/6 (49%), 6/7 (37%), and 7/7 (14%). Initially, 11 (6/6) pts were excluded. A further 7 (6/7) and 3 (7/7) pts withdrew consent or were not eligible. To date, we have treated and evaluated 14 pts for toxicity (table 1). Of the two 7/7 pts at dose level 1, one had DLT [G4 ANC for 6 days, G4 nausea (N), vomiting (V), diarrhea (D) and febrile neutropenia (FN)] while another developed cycle 2 G3 FN and infection. For 6/7 pts, no DLT was seen at dose level 1, however 1/3 pts had DLT at dose level 2 (G3 D, N, V and G4 dehydration and hyponatremia). For 6/6 pts, no DLT was observed and the only G3 toxicity was neutropenia (1 pt at each dose level). Per protocol, dose level 1 was closed to 7/7 pts and accrual is ongoing for 7/7 pts (dose level -2), 6/7 pts (dose level 2), and 6/6 pts (dose level 4). Conclusion: The UGT1A1 *28 genotype affects the tolerable dose of the combination of CPT-11, Oxal, and Cap. The results of dose de-escalation (UGT1A1 7/7) and dose escalation (UGT1A1 6/7 and 6/6) will be reported. Dose escalation schema by UGT1A1 genotype Dose Level Dose (mg/m2/day) UGT1A1 7/7 UGT1A1 6/7 UGT1A1 6/6 -2 CPT-11 75 Oxal 85 Cap 400 Accruing - - 1 CPT-11 150 Oxal 85 Cap 400 2 (1) Closed 3 - 2 CPT-11 150 Oxal 85 Cap 800 - 3 (1) Accruing 3 3 CPT-11 150 Oxal 120 Cap 800 - - 3 4 CPT-11 150 Oxal 120 Cap 1600 - - Accruing Patients in parentheses experienced DLT in cycle 1 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Roche, Sanofi Roche, Sanofi Sanofi
Changing patterns of care for locally advanced non-small cell lung cancer (NSCLC): Implications for quality initiatives.
Authors: Matthew David Hall, Peter Edward Gabriel, Wensheng Guo, Sandhya Upasani, Marjorie van der Pas, Timothy E. Schultheiss, Joel W. Goldwein, John Paul Christodouleas
Journal: Journal of Clinical Oncology (2016)

302 Background: Our purpose was to assess the utilization of dose escalated radiotherapy (RT) in Stage III NSCLC patients in the United States from 2004-2013, a period when no Level 1 evidence on dose escalation was published. Methods: Data on all NSCLC patients treated with RT were extracted from the National Oncology Data Alliance (NODA), a pooled database of cancer registries from &gt;150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER, but also contains RT dose fields that are manually verified by trained staff. Search algorithms to identify patients with complete RT dose data and who met the RTOG 0617 eligibility criteria were developed and validated by manual chart review at two institutions. The search algorithm positive predictive values for RT dose and RTOG 0617 eligibility were 97% and 91%, respectively. The primary endpoint was utilization of dose escalated RT, defined as &gt;70 Gy. Multivariate logistic regression (MVA) was used to measure the association of treatment year with dose escalated RT use in two predefined periods straddling the early closure of RTOG 0617 on 6/17/2011: Period 1 2004-2010 and Period 2 2010-2013. To address potential limitations in generalizability, we repeated the same analysis in the National Cancer Database (NCDB). Results: The percentage of patients treated with &gt;70 Gy increased monotonically from 22% in 2004 to 37% in 2010 and then declined to 20% in 2012. On MVA, increasing utilization of doses &gt;70 Gy was observed during Period 1 (p&lt;0.001) followed by decreasing use during Period 2 (p=0.002), after adjusting for the effects of other significant patient and hospital level variables. A similar utilization pattern was observed in the NCDB. After adjusting for age and comorbidities, significant changes in the mean RT dose prescribed compared to the 3-year moving average could have been detected in 2008 and 2012, if dose had been prospectively monitored in the NODA. Conclusions: Our study suggests that US radiation oncologists increasingly utilized RT doses &gt;70 Gy in Stage III NSCLC patients treated from 2004-2010 followed by a decline after 2010. RT dose may be an important standardization metric in national quality initiatives.
Final results of phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in metastatic colorectal cancer (mCRC).
Authors: Kentaro Yamazaki, Tomohiro Nishina, Takeshi Kato, Takayuki Yoshino, Yoshinori Miyata, Taito Esaki, Toshikazu Moriwaki, Narikazu Boku, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2014)

574 Background: The SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) demonstrated a promising activity with tolerated toxicities compared to mFOLFOX6 in a randomized phase II study for mCRC. We previously reported the promising results of a phase II study of SOL+BV in Gastrointestinal Cancers Symposium 2012 (Kato T, et al.) focusing on early clinical outcomes, overall response rate (ORR), progression free survival (PFS) and safety. The final follow-up (cut-off date Dec 2012) has been completed, and we report up-dated overall survival (OS) and the impact of early objective tumor response (EOTR) on OS in the present report. Methods: The main inclusion criteria were; (1) metastatic colorectal adenocarcinoma, (2) age ≥20 years, (3) no prior chemotherapy, (4) target lesion (RECIST v1.0), (5) ECOG PS 0-1, 6) written informed consent. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week. Oxaliplatin (85 mg/m 2 ) and BV (5 mg/kg) were administered on day 1. This treatment was repeated every 2 weeks. The primary endpoint was ORR confirmed by the independent review committee according to RECIST v1.0. This trial was supported by Taiho Pharmaceutical CO, LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881). Results: From Oct 2009 to Apr 2010, 31 pts were enrolled. Of the eligible 29 pts, median age was 62; PS 0/1 was 24/5; number of metastatic organs 1/≥2 was 15/14. ORR was 86% (95%CI, 68-96), and the median PFS was 15 months (95%CI, 10-26). OS has not reached median with a median follow-up time of 34 months. Two-year survival rate was 72%. EOTR (RECIST sum ≥30% shrinkage) at 6-weeks was observed in 35% of pts. Two-year survival rate in these pts with an EOTR at 6-weeks was 80%, while in other pts without an EOTR at 6-weeks was 68%. The curative resection rate of metastatic lesions was 28%. The incidence (≥10%) of grade 3/4 adverse drug reactions were; neutropenia 20%, hypertension 23%, anorexia 20%, fatigue 17%, diarrhea 10%, and sensory neuropathy 53%. Conclusions: The SOL+BV regimen showed the promising activity for mCRC. The high proportion of EOTR might lead to long survival. Further evaluation of this regimen would be warranted. Clinical trial information: 090881.
Activity of R1507, a monoclonal antibody to the insulin-like growth factor-1 receptor (IGF1R), in patients (pts) with recurrent or refractory Ewing's sarcoma family of tumors (ESFT): Results of a phase II SARC study.
Authors: A. S. Pappo, S. Patel, J. Crowley, D. K. Reinke, A. P. Staddon, K. Kuenkele, S. P. Chawla, R. S. Benjamin, L. J. Helman, L. H. Baker
Journal: Journal of Clinical Oncology (2010)

10000 Background: IGF has been implicated in sarcoma development. Cell line and nude mouse experiments of antibody mediated inhibition of IGF1R demonstrated significant activity in single agent and in combination chemotherapy studies. Antibody mediated inhibition of IGF1R induced clinical responses in ESFT pts in several phase I studies. R1507 monotherapy was explored in this phase II single arm trial. Methods: Eligibility included recurrent/refractory, measurable disease, age ≥ 2 yrs, life expectancy ≥ 6 weeks, Karnofsky PS ≥ 70, adequate renal, hepatic and bone marrow function. R1507 was administered IV at 9 mg/kg over one hour weekly. Response was assessed by WHO criteria every 6 wks × 4 and every 12 wks thereafter. Results: From 12/07-8/09, 125 patients with ESFT from 31 sarcoma centers in the US, Europe, and Australia were treated. Age ranged from 3-78 yrs (median=25 yrs) and 83 (66%) were male. 18 pts had CR or PR (14.4%). 12 pts responded at least 6 weeks with a median duration of 25 weeks. Median survival was 7.6 months. Gr 3-4 toxicities occurred in 16 pts including: diarrhea (2), anemia (2), thrombocytopenia (2), and neutropenia (2). Importantly, there were no gr 3-4 hyperglycemic or cardiacevents reported. Many investigators noted the need for weekly IV administration was a significant burden to pts and caregivers. Conclusions: R1507 is active as monotherapy in pts with metastatic ESFT. A major task moving forward with IGFIR Ab therapy in ESFT will be to identify predictors of response so that pt enrichment strategies can be undertaken. Studies combining this new drug with other effective therapies earlier in the treatment of disease are predicted to have significant clinical impact. Finally, studies are needed to address mechanisms of resistance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche
Oncology patients in the health care safety net: Is it too late for early palliative care?
Authors: Heather A. Harris, Anne Kinderman, Leslie Safier
Journal: Journal of Clinical Oncology (2016)

128 Background: Studies have suggested that uninsured and Medicaid patients are more likely to present with late-stage cancer than Medicare patients, and may be more likely to be admitted urgently or emergently. However, studies of palliative care interventions for cancer patients suggest that the greatest impact can be achieved if these services begin “early” (≥ 90 days prior to death). In our urban public hospital, we examined where patients receive their initial cancer diagnosis, and at what stage they are diagnosed, in order to determine how to best implement community-based palliative care services. Methods: Retrospective cohort analysis of cancer patients diagnosed over a five year period. Hospital tumor registry data were used to determine the location of diagnosis (inpatient vs. outpatient), stage and type of cancer at diagnosis, and patient status at the end of the study period (alive vs. deceased). Results: Of the 2,928 patients diagnosed with cancer, 26% of patients (n = 759) were diagnosed while hospitalized. Patients who received their diagnosis while hospitalized were more likely to be diagnosed with stage 3-4 disease (49%, n = 372), vs. stage 0-1 (21%, n = 163). 25% of patients who received their diagnosis in the inpatient setting died within 90 days of initial diagnosis. Patients diagnosed in the outpatient setting were more likely to be diagnosed with stage 0-1 (40%, n = 865), vs. stage 3-4 (32%, n = 688). Patients diagnosed while hospitalized were 2.9 times more likely to be diagnosed with late stage disease, compared to those diagnosed as outpatients (95% CI 2.3-3.5, p &lt; 0.0001). Conclusions: A large minority of patients received their cancer diagnosis while hospitalized, and were more likely to be diagnosed with late-stage disease. Additionally, a significant proportion of these patients died within 90 days of their initial diagnosis. In order to provide "early" palliative care for cancer patients in public hospitals, palliative care programs may need to offer initial consultation visits while patients are hospitalized, and then connect them with prompt outpatient follow-up. Safety net programs with palliative care services for cancer patients should emphasize continuity across inpatient and outpatient settings.