tbuckley/cabot-search huggingface dataset:
Phase II study of dovitinib in patients (Pts) progressing on anti-vascular endothelial growth factor (VEGF) therapy.
Authors: Thomas John Semrad, Edward Jae-hoon Kim, Michael S. Tanaka, Jacob Sands, Chris Roberts, Stephanie H. Astrow, Craig Stephens, Miriana Moran, Rebekah Burich, Yu Li, David R. Gandara, Primo Lara, Philip C. Mack
Journal: Journal of Clinical Oncology (2016)

616 Background: Prior work identified the fibroblast growth factor (FGF) pathway as a mediator of resistance to anti-VEGF therapy. We tested dovitinib, an oral inhibitor of both FGFRs and VEGFRs in pts progressing on anti-VEGF treatment. Methods: Pts with measurable advanced colorectal cancer (CRC) or non-small cell lung cancer (NSCLC) with progression despite treatment with an anti-VEGF agent within 56 days, good performance status (PS) and adequate organ function were eligible. A pre-treatment tumor biopsy was followed by treatment with dovitinib 500 mg on a 5 day on / 2 day off schedule for 28-day cycles. The primary endpoint of response (RECIST 1.1) was evaluated every 2 cycles. Secondary endpoints included toxicity and the disease control rate at 8 weeks. Intratumor mRNA expression was analyzed using a Next Generation Sequencing based expression array and circulating angiogenic factors analyzed by a multiplex bead-based assays and ELISAs. Results: Ten pts (9 CRC, 1 NSCLC) treated previously with bevacizumab (8) or ziv-aflibercept (2) enrolled. The study closed with termination of dovitinib development. No responses were observed in 7 evaluable pts; 3 withdrew consent during cycle 1. The best response was stable disease in 1 patient. Common toxicities included gastrointestinal, metabolic, and biochemical derangements. All pts experienced at least 1 grade 3 or higher treatment-related adverse event, most commonly fatigue, elevated GGT, and lymphopenia. Expression of multiple angiogenic mediators was common in tumors progressing on anti-VEGF therapy including high levels of FGFR1 and VEGFA. Dovitinib modulated circulating VEGF pathway components; however, no hyperphosphatemia was observed and plasma FGF2 increased continuously. Conclusions: We found no evidence for the activity of dovitinib in pts with CRC progressing on anti-VEGF therapy and could not confirm potent FGFR inhibition. Toxicities were significant. In tumors progressing despite anti-VEGF therapy, a multitude of pro-angiogenic mediators are expressed, including members of the FGF pathway. Clinical trial information: NCT01676714.
Salvage brachytherapy and short-term androgen deprivation therapy for locally recurrent prostate cancer after external beam irradiation
Authors: W. Wong, S. Buskirk, S. Schild, P. Karin
Journal: Journal of Clinical Oncology (2005)

4788 Background: Patients (pts) who develop local relapse of prostate cancer after external beam irradiation (EBRT) are often treated with androgen deprivation therapy (ADT) because of their advanced age and co-morbid conditions. Salvage treatment with curative intent may be considered in selected pts. We have treated 13 pts with combined brachytherapy (BT) and short-term ADT between 1999 and 2002. Methods: The median pre-EBRT PSA was 12 ng/ml (range: 4–24 ng/ml) and the median dose of prior EBRT was 68 Gy. At the time of biochemical (6 pts) or palpable local failure (7 pts), prostate biopsy was obtained to confirm local relapse. The median time between EBRT to biopsy was 5.9 years. Bone scans and CT scans were negative for metastasis. Five pts were treated on a protocol that combined 3 months of neoadjuvant and 6 months of adjuvant leuprolide with I-125 BT. The prescribed dose was 126 Gy. Another 8 pts were treated with neoadjuvant leuprolide (median: 4 months) before Pd-103 BT. The prescribed dose was 103.5–112.5 Gy. The ASTRO definition of biochemical failure (PSAF) was used. Toxicity was graded by a modified RTOG scale. Results: The median age of was 67 (range: 62–80). The Gleason score of the biopsies at relapse were 6 (5 pts), 7 (5 pts), 8 (2 pts), and 9 (1 pt). The median PSA at the time of relapse was 4.7 ng/ml (range: 1.2–11.8 ng/ml). The median follow-up time was 34 months (range:13–60 months). Two pts developed PSAF, and the 4-year actuarial biochemical control rate was 79%. The were no clinically apparent local or distant failures. One pt died of intercurrent disease. Grade 3 GU toxicity developed in 5 pts (38%), requiring minor surgical procedures. One pt (8%) had grade 4 GU toxicity, resulting in an ileal conduit. No patient developed grade 3 GI toxicity. On univariate analysis, biochemical control was not significantly associated with Gleason score, PSA or T-stage at time of local relapse, probably due to the small number of pts. Conclusions: Our series suggests that biochemical control can be achieved with salvage brachytherapy and short-term ADT in selected patients with local relapse after prior EBRT. The treatment resulted in 38% grade 3 and 8% grade 4 GU toxicity. No significant financial relationships to disclose.
Improving the quality of the consenting and education process for patients starting on oral oncology medications.
Authors: Lauren Azure Zatarain, Jessica Ashford, David Bivens
Journal: Journal of Clinical Oncology (2016)

82 Background: Oral oncology medication prescribing is on the rise nationwide. Given that these medications are self-administered, drug compliance is a concern. Appropriate patient education directly impacts drug adherence. Prior to the process improvement initiative in our community based medical oncology clinic, implied consent was obtained while educating patients on side effects and written informed consent was documented 0% of the time. This creates a patient safety and risk management problem. Methods: Our clinic implemented a new process for consenting and educating patients starting on new oral oncology medications from April – October 2015. The plan/do/study/act performance improvement technique was utilized. A new consent form was created for oral oncology medications meeting ASCO/ONS safety standards. The consent and education packets were placed centrally in the office and coincided with an initiative to improve consenting for IV chemotherapy. Providers were in-serviced to contact the nurse prior to patients exiting clinic to initiate the new prescription and begin the patient education process. Reminder checklists were placed in exam rooms to trigger the provider to communicate with nursing staff. Outcome measures included data on the percent of patients with written informed consent in health record and percent of patients with patient education handouts in health record prior to drug start. Data on percent of patients for whom the provider notified nurse prior to end of clinic visit were collected as a balance measure. Results: Over a 6 month period, 101 consecutive patients initiated on oral oncology drugs were included in the data analysis. The baseline mean improved from 0% to 75% for obtaining written informed consent (p chart, 3 sigma). The baseline mean improved from 37% to 80% for documenting patient education in health record prior to oral oncology medication start (p chart, 3 sigma). Conclusions: There was significant improvement in obtaining written informed consent and providing patient education prior to oral oncology drug start after implementation of new clinic processes.
Minimizing radiochemotherapy induced acute skin and mucosal toxicity in head and neck cancer patients treated by Dead Sea products
Authors: R. Ben-Yosef, A. Vexler, N. Asna, A. Khafif, D. Sarid, D. Matceyevsky
Journal: Journal of Clinical Oncology (2005)

5606 Background: Mucositis and skin damage are frequently presented in patients receiving radio-chemotherapy. Various Dead Sea Products that contain minerals and various unique substances are effective in treating various skin diseases as psoriasis. In this study we evaluate its effectiveness in patients treated with radio-chemotherapy to head and neck tumors. Patients and Methods: Patients with head and neck tumors were recruited for this study. The trial group (20 pts) and the control group (30 pts) were matched by age, tumor site and treatment type. The irradiation was delivered using a linear accelerator operated on 6 MV photon beam. The total dose varied from 50 to 75 Gy and the dose per fraction was 1.8–2.0 Gy. The chemotherapy was mainly consisted of carboplatin given once a week at a dose of AUC-2. The Dead Sea products contained mouthwash and a skin cream (Dr Nona Ltd, Israel). Both were used three times a day started a week before, during and up to two weeks after completion of treatment. Skin and mucosal toxicities were evaluated using the RTOG toxicity (1998) criteria. The overall treatment time was documented in all patients and treatment breaks (>3 days) due to acute side effects were recorded. The local ethical committee approved this study. Results: In the trial group mucositis and skin damage of grade I-II were noted in 11 (55%) and 12 (60%) out of 20 patients respectively. None had grade III-IV toxicity. These toxicities led to a 15 (range 3–21) days of treatment break in 3 (15%) patients. In the control group 17 out of 30 (57%) patients had mucositis of grade I-II and 4 (13%) had grade III-IV. A skin damage of grade I-II and grade III-IV was noted in 11 (37%) and in 5 (17%) patients respectively. A treatment break of 15.1 (range 5–33) days was seen in 12 (40%) patients. The overall toxicity- described by grade III-IV skin toxicity (0% vs 17% p=0.07), grade III-IV mucosal toxicity (0% vs 13% p=0.14) and by number of patients with treatment breaks (15% vs 40% p=0.07)- was lower in the trial group. Conclusions: Dead Sea products, tested in this study, seem to decrease the severity and the duration of skin and mucosal toxicity in radio-chemotherapy treated patients with head and neck tumors. No significant financial relationships to disclose.
Randomized phase II trial of panitumumab, erlotinib, and gemcitabine (PGE) versus erlotinib-gemcitabine (GE) in patients with untreated, metastatic pancreatic adenocarcinoma.
Authors: G. P. Kim, N. R. Foster, M. Salim, P. J. Flynn, D. F. Moore, R. Zon, R. B. Mowat, M. Wiesenfeld, A. E. McCullough, S. R. Alberts
Journal: Journal of Clinical Oncology (2011)

4030 Background: Dual inhibition of the EGFR pathway using erlotinib and panitumumab results in greater antitumor activity in preclinical pancreatic cancer models. A trial to evaluate this approach was conducted. Methods: Safety analysis initially performed with 6 patients (pts) at P 4 mg/kg every two weeks, E 100 mg daily, G 1,000 mg/m² weekly of a 28-day cycle. PGE well tolerated with grade 3 fatigue as only dose-limiting toxicity. Pts then randomized to either PGE or GE. Primary endpoint OS with 1-sided log-rank test, p=0.20 significance, 80% power. Eligibility: no prior chemo, ECOG PS 0-1, bili <2x UL, AST <2.5x UL. Restaging every 2 cycles. Results: 92 evaluable pts (46-PGE; 46-PE) randomized from January to August, 2010 at 26 different sites. Median age- 61 years; 65% male; ECOG PS 0/1 (51/49%). No significant differences in baseline characteristics. Median follow-up 6 months. OS significantly improved in the PGE arm versus GE arm (HR=0.61 (95% CI: 0.35, 1.06); median OS: PGE=8.4 months, GE=4.0 months; p=0.077). PFS and subsequent treatment similar between arms. 46 (50%) had a maximum grade 3 AE (at least possibly related), and 18 (20%) maximum grade 4. PGE had significantly higher rates of non-hematologic grade 3 toxicity (61% vs. 30%; p =0.003), mainly grade 3 rash (PGE: 28%, GE: 9%; p=0.03). Grade 4 toxicity rates were similar between arms (p=0.58). Common grade 4 AEs- thrombosis (4 pts) and thrombocytopenia (3 pts). One grade 5 toxicity occurred in PGE arm- duodenal hemorrhage (possibly related). 81 patients (88%; 40-PGE, 41-GE) ended treatment; 57 (70%) disease progression (26-PGE, 31-GE), AEs (16%), pt refusal (9%), other (5%). Conclusions: This study involved an initial run-in design to define tolerable doses of dual EGFR inhibitors, PGE, in metastatic pancreatic cancer patients. PGE showed significantly improved OS compared to GE, with similar PFS. PGE also had significantly higher grade 3 non-hematologic toxicity, specifically rash. K-RAS mutation analyses using stool and tissue are ongoing and correlations with survival will be presented. The dual anti-EGFR approach in pancreatic cancer results in a survival benefit.
Prognostic and predictive effect of COX-2 expression in appendiceal adenocarcinomas.
Authors: Kanwal Pratap Singh Raghav, Syed Mohammad Ali Kazmi, Aditya V. Shetty, Melissa W. Taggart, Keith F. Fournier, Richard E. Royal, Paul F. Mansfield, Cathy Eng, Robert A. Wolff, Michael J. Overman
Journal: Journal of Clinical Oncology (2012)

526 Background: Cyclooxygenase-2 (COX-2), an inducible isoenzyme, is upregulated in inflammation and involved in cancer progression by promoting angiogenesis, cell proliferation and migration and by inhibiting apoptosis. COX-2 is implicated in colorectal tumorigenesis and by extension COX-2 expression testing and therapeutic inhibition has been considered in appendiceal adenocarcinomas (AAs). However, its role in this setting has never been well studied. The purpose of our study was to investigate COX-2 expression in AAs and to evaluate its prognostic and predictive significance. Methods: We performed a retrospective review of 607 patients with AAs treated at MD Anderson Cancer Center between 2002 and 2010. Immunohistochemistry was performed for COX-2 expression (COX2 mAb Clone CX229, Cayman Chemical) in 49 (8%) patients. Thirty (61%) stained positive and 19 (39%) showed no staining. Kaplan-Meier product limit method and log-rank test were used to estimate overall survival (OS) and to determine association between OS, COX-2 expression and other characteristics. Results: Median age at diagnosis was 47 yrs (range 34-78 yrs). Grade (P = 0.003), completeness of cytoreduction score (P = 0.010) and stage (P = 0.023) were significantly associated with OS. Median OS for patients with COX-2 positive and COX-2 negative tumors was 58.3 and 42.8 months, respectively (P = 0.232). Nine COX-2 positive patients received celecoxib (selective COX-2 inhibitor) in combination with other chemotherapy. Mean treatment duration was 5.5 months with best radiographic response being stable disease in 7 patients. Reduction in tumor markers (CEA or CA19-9) was seen in 7 cases (median reduction of 30%). Similar treatment duration (6.6 months), rate of stable disease (6/8 pts) and tumor marker reduction (7/8 pts) was seen on the preceding non-celecoxib containing chemotherapy in these patients. Median OS, with and without COX-2 inhibition, was 55.7 and 57.6 months respectively (P = 0.57). Conclusions: In this cohort, COX-2 expression is not a significant prognostic factor in AAs. Benefit from COX-2 inhibition in COX-2 expressing AAs is unclear. Current data does not support the routine use of either COX-2 testing or COX-2 inhibition therapy in AAs.
Hematopoietic Stem Cells Mobilization by G-CSF and LTB4 Was Significantly Suppressed by an Oxygen Radical Scavenger or an Inhibitor of NADPH Oxidase.
Authors: Yeung-Chul Mun, Soo Ah Oh, Kyoung-Eun Lee, Eun-Sun Yoo, Hye-Jung Chang, Moon-Young Choi, Jee-Young Ahn, Jae-Hong Kim, Chu-Myong Seong
Journal: Blood (2007)
Incidence, management, and resolution of stomatitis and noninfectious pneumonitis in BOLERO-2.
Authors: Alejandra T. Perez
Journal: Journal of Clinical Oncology (2013)

159 Background: Although the mTOR inhibitor everolimus (EVE) was generally well tolerated in combination with exemestane (EXE) in patients (pts) with HR+/HER2– advanced breast cancer, stomatitis and noninfectious pneumonitis (NIP) are the most clinically relevant and potentially dose-limiting toxicities. The incidence, grade, and clinical course of stomatitis and NIP among pts participating in the BOLERO-2 study are described. Methods: Pts were randomized 2:1 to receive EVE + EXE or placebo (PBO) + EXE. Incidence and severity of stomatitis and NIP, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: Stomatitis (any grade) occurred more frequently with EVE + EXE than with PBO + EXE (59% vs 12%, respectively). Grade 3 stomatitis occurred in 8% vs 1% of EVE + EXE vs PBO + EXE pts, respectively; no grade 4 events were reported. Onset of grade ≥ 2 stomatitis after treatment initiation was earlier for EVE + EXE arm vs PBO + EXE: median time was 15 d vs 24 d, respectively. For the EVE + EXE arm, 97% of pts with grade 3 stomatitis (n = 38) improved to ≤1 after a median of 13 d. Complete resolution was observed in 82% of pts after a median of 38 d. For the PBO + EXE arm, all pts with grade 3 stomatitis (n = 2) improved to ≤1 after a median of 18 d. Complete resolution was observed after a median of 29 d. 24% of pts on EVE + EXE required dose interruptions/adjustments vs 1% of pts on PBO + EXE, and 3% of pts (n = 13) discontinued EVE + EXE vs &lt;1% of pts (n = 1) discontinuing PBO + EXE, all related to stomatitis. Overall, 16% in the EVE + EXE vs 0% in the PBO + EXE groups had a diagnosis consistent with NIP. For EVE + EXE, grade 1, 2, and 3 NIP occurred in 7%, 6%, and 3% of pts, respectively; no grade 4 events were reported. Complete resolution of NIP to grade ≤1 was recorded for all but 4 pts for whom NIP was still observed at last follow-up before study discontinuation. Overall, in the EVE + EXE arm, NIP was reason for dose interruption and treatment discontinuation in 7.5% and 5.6% of pts, respectively. Conclusions: In the BOLERO-2 study, stomatitis and NIP were of mild to moderate intensity and were generally reversible. Most incidents were successfully managed with palliative interventions and temporary dose modifications. Clinical trial information: NCT00863655.
Natural history of metastatic breast cancer at presentation (PMBC) versus recurrence (RMBC): A comparison of time of disease control (TDC).
Authors: H. Singh, C. O. Ruud, J. Reynolds
Journal: Journal of Clinical Oncology (2011)

e16643 Background: The benefit of subsequent lines of systemic treatment in metastatic breast cancer (MBC) is not well described in the literature. The objective of this study is to compare PMBC to RMBC in terms of TDC and mean survival. Methods: This is an IRB-approved internal retrospective data analysis utilizing electronic medical records and the American College of Surgeons tumor registry data at Scott & White Memorial Hospital. Patients selected were those with metastatic breast cancer diagnosed between 2000 and 2009. Of the 428 identified, a random sample of 139 patients was selected, matched by proportion of PMBC and RMBC as compared to the 428. Inclusion criteria were those treated with at least one line of standard systemic therapy after metastatic diagnosis. Exclusion criteria were male gender and incomplete treatment data. IBM SPSS statistical software was utilized for descriptive analysis. Paired T-tests were performed for comparative analysis of TDC. TDC is defined as the time between two consecutive lines of treatment. Results: The study included 111 of the 139 initial subjects. Of those excluded, 6 lacked sufficient treatment data, 21 did not undergo first line treatment after metastatic diagnosis, and 1 was male. 38 were diagnosed at time of metastasis (PMBC), while 73 patients had a prior diagnosis of breast cancer and recurred with metastasis (RMBC). Three patients in each PMBC and RMBC group were not included in the mean survival analysis due to loss of follow up. There was no statistically significant difference for the TDC between consecutive lines of therapy within PMBC or RMBC. In comparison of PMBC and RMBC, the TDC for each line (1-5) of therapy and mean survival also did not differ. Conclusions: The natural history of PMBC and RMBC measured by TDC and mean survival did not differ. Line of treatment 1 2 3 4 5 Mean survival (months) PMBC N 25 20 14 7 3 25.9 Mean TDC (months) 9.6 5.4 8.8 4.4 5.0 10 of 36 alive RMBC N 51 29 17 13 6 26.2 Mean TDC (months) 10.0 6.5 6.0 9.0 6.1 21 of 69 alive
Population-based pan-Canadian EGFR-mutation testing program.
Authors: M. S. Tsao, D. Ionescu, G. Chong, A. M. Magliocco, D. Soulieres, D. Hwang, S. Young, C. Wei, I. Bosdet, A. Karsan, A. Spatz, S. Kamel-Reid
Journal: Journal of Clinical Oncology (2011)

e18017 Background: Gefitinib was licensed in Canada for the first line treatment of advanced non-small cell lung carcinoma (NSCLC) patients with EGFR tyrosine kinase mutation. Methods: A Pan-Canadian EGFR mutation testing program was established to enable the routine testing of patients who might be eligible for first line gefitinib therapy. Five regional clinical diagnostic centres across Canada were selected for this pilot testing network. Initial efforts included the standardization of testing protocols, selection of assay platforms and evaluation/confirmation of individual laboratory's assay performance. Testing requests were initiated by the treating oncologists for patients with non-squamous NSCLC histology. In a majority of cases, archival samples resided in the primary care hospitals and required submission to their designated regional test centres. Only Exon-19 deletions and the exon-21 L858R mutation were evaluated, and tests were conducted on archival paraffin embedded tumor samples, which could include cytology cell blocks. Results: From March 18 to November 30, 2010, a total of 1869 requests for mutation testing were made. A total of 1716 samples were received by the test centres. Following pre-test histological evaluation of the submitted samples, mutation testing was conducted on 1588 (92.5%) samples. Altogether 279 (17.6%) were found positive for EGFR exon-19 deletion or exon 21 L858R mutation. The median time for the receipt of samples by the test centres was 7 days, and for test centres to complete and report the result was 11 days. Information on the characteristics of test samples in relation to test outcomes will be presented. Conclusions: Canadian population wide EGFR mutation testing in advanced NSCLC patients is feasible and identified 17.6% patients with EGFR sensitizing mutation-positive tumors. The EGFR mutation testing program is supported by AstraZeneca Canada.