tbuckley/cabot-search huggingface dataset:
Variability in the reporting of dermatologic adverse reactions (dADRs) to EGFR inhibitors cetuximab (C) and panitumumab (P) in the treatment of metastatic colorectal cancer (mCRC)
Authors: S. B. Hammerman, D. P. West, C. L. Bennett, M. E. Lacouture
Journal: Journal of Clinical Oncology (2008)

15045 Background: The epidermal growth factor receptor inhibitors(EGFRIs) C and P have demonstrated clinical activity against mCRC. Despite these benefits, up to 90% of patients experience dADRs, which can decrease their quality of life and alter antineoplastic therapy, both of which can affect outcome. There is anecdotal evidence suggesting inconsistency in the reporting of these events in clinical trials, which has led to deficient data on incidence and risk factors. Thus, our study examines the variability of EGFRI induced dADR reporting in mCRC clinical trials. Methods: The Pubmed MEDLINE database was searched for relevant information. Search terms included “C” and “P”, and “colorectal cancer”, and limited to Phase II-III clinical trials. Data obtained included regimen, number of discrete dADRs, and rash-survival correlation. Results: All dADRs reported were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE V.3.0). Our search yielded 31 results for C and 7 for P. Of 31 C trials, 11 (35%) reported between 1 and 3 dADRs. One dADR was reported in 6 trials (55%), 2 dADRs in 4 (36%) and 3 dADRs (rash, paronychia, and pruritus) were reported in 1 (9%). Rash was reported in all (11 of 11) trials, paronychia in 5 of 11, and pruritus in 1 of the 11. Of 7 P trials, 3 (43%) reported between 2–7 dADRs. Two dADRs were reported in 1 trial (33%), 6 dADRs in 1 (33%), and 7 dADRs (rash, pruritus, dry skin, paronychia, dermatitis acneiform, skin desquamation, skin fissures, and erythema) in 1 (33%). All of the reports mentioned rash as a side effect. However, they were not consistent in the manner in which rash was reported. CTCAE toxicity grading was completely reported in 82% of C trials and 100% of P. The use of tabulated data to report dADRs was present in 82% of C trials and 100% of P trials. Of note, a positive rash-survival correlation was noted in 45.5% of C trials and 66% of P. Conclusions: Our results indicate that there is considerable variability of EGFRI-induced dADR reporting in mCRC trials. This impedes the ability of Oncologists to provide accurate pre- therapy counseling to their patients. To improve data reliability, current standards should be revised. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc, ImClone Systems, Onyx Pharma Amgen Inc, Bayer Pharmaceuticals, ImClone Systems
Ovarian cancer treatment in the New York City municipal hospital system
Authors: L. R. Boyd, A. P. Novetsky, J. P. Curtin
Journal: Journal of Clinical Oncology (2009)

5569 Background: OC patients (pts) from minority groups/lower socioeconomic strata are reported to have poorer outcomes. New York City (NYC) Health and Hospitals Corporation (HHC) has 11 municipal hospitals. We evaluated surgical management of OC pts in HHC hospitals. Methods: The New York State SPARCS database of admissions was queried for OC pts in the years 2001 to 2006. Pts from HHC were compared to pts from all other NYC hospitals (other cohort). Pt demographics, procedure performed, emergent vs. scheduled admission, length of stay, and hospital charges were compared utilizing chi-square. A comorbidity index was applied to both cohorts. Surgeons were stratified by subspecialty training and OC case volume. Results: 6,010 admissions for OC were identified. 3,624 were major surgical procedures: 187 from the HHC cohort and 3,436 from the other cohort. Demographics for HHC vs other cohort, respectively: Caucasian 37 (20%) vs 2,224 (65%); African-American (AA): 64 (34%) vs 460 (13%); Asian 20 (11%) vs 181 (5%); other: 66 (35%) vs 286 (8%); unknown 0 vs. 286 (8%) (p&lt; 0.001). Payors for the HHC vs other cohort, respectively: Medicaid 108/187 (57%) vs 279/3,437 (8%); Medicare 22/187 (12%) vs 872/3,437 (25%); private insurance 38/187 (20%) vs 2,244/3,437 (65%); self-pay 18/187 (10%) vs 40/3,437 (1%) (p &lt; 0.001). Urgent admissions were 96/187 (51%) of HHC cohort vs 902/3,436 (26%) of other cohort (p &lt; 0.001). There were no differences in comorbidity rating or procedures performed. Subspecialty surgeons were documented for 59/187 (32%) of HHC cohort vs 1,839/3,437 (53%) of other cohort (p &lt; 0.001). The majority of surgeons performed less than two OC cases over the six year period, however surgeons with cases at HHC hospitals were more likely to be represented in the top 15% of total case volume (25% vs 14%, p &lt; 0.01) due to affiliations with academic centers. Conclusions: Pts in HHC cohort were more likely to be AA, have an urgent admission and less likely to have insurance or have a gynecologic oncologist as a surgeon. However there is evidence of centralized care for some in the HHC cohort. Despite the limitations associated with using a large database, clear differences were seen in the patterns of care between municipal and all other NYC OC pts. Studies to document outcomes and further optimize care within the HHC hospital system are ongoing. No significant financial relationships to disclose.
Comparison of adverse events of erlotinib with those of gefitinib in Japanese patients with NSCLC.
Authors: T. Suzumura, S. Kudoh, T. Kimura, K. Umekawa, H. Tanaka, S. Mitsuoka, N. Yoshimura, K. Hirata
Journal: Journal of Clinical Oncology (2010)

7566 Background: Liver dysfunction, diarrhea, skin disorder, and interstitial pneumonia are known as adverse events of EGFR-TKI. However, clinical trials of gefitinib reported difference profiles in adverse events compared to those of erlotinib. The hypothesis is that there may be some differences in adverse event of gefitinib and erlotinib. Methods: We retrospectively analyzed mainly adverse events, patient backgrounds, treatment efficacy and treatment periods for patients treated erlotinib or gefitinib for 30 or more days. Results: Forty-six patients were received erlotinib therapy and 41 patients were received gefitinib therapy in 2007 to 2009 in our hospital. There were no significant differences in patient backgrounds except for EGFR mutations. Erlotinib was administered in more patients without mutations than gefitinib (p = 0.003). Skin disorders had significant differences of erlotinib and gefitinib with 96% and 73% in all grades, respectively (p < 0.001). Skin disorders in grade 2/3 of erlotinib and gefitinib were 54% and 15%, respectively (p < 0.001). On the contrary, liver dysfunctions of erlotinib and gefitinib were 30% and 73% in all grades, respectively (p < 0.001). Liver dysfunctions in grade 2/3 of erlotinib and gefitinib were 17% and 29% with no significant difference (p = 0.212). No significant difference was seen in patients between erlotinib and gefitinib in any grades of diarrhea. The patients with gefitinib had tendencies of longer overall survivals and progression free survivals than those with erlotinib (p = 0.084, p = 0.098). Conclusions: Erlotinib had higher rate of skin disorders and lower rate of liver dysfunctions than gefitinib. The patients who caused liver dysfunctions by gefitinib may have a decrease of liver damages when the treatment was changed to erlotinib. No significant financial relationships to disclose.
Toxicity and cosmesis after oncoplastic surgery and interstitial brachytherapy.
Authors: Linda A. Smith, Robert R. Kuske
Journal: Journal of Clinical Oncology (2014)

89 Background: Oncoplastic surgery fuses breast cancer surgical and reconstructive techniques, both simple and complex. Following sculpting and removing the appropriate malignancy, tissue rearrangement is utilized to minimize the dead space. PBI with brachytherapy provides excellent tumor control in this population. This study investigates cosmetic outcome and toxicity in select stage 0, 1, and 2 breast cancers treated by a single breast surgeon and radiation oncologist. Methods: 140 women were treated between May 2010 and December 2013 with breast conservation, sentinel node biopsy (SNB), and interstitial brachytherapy. Selection criteria included women of any age, any subtype, tumor size less than &lt; 3 cm, N0 or N1mic, with excision margins &gt; 1 mm. Strict modified Harvard cosmesis scale was used by direct examination by the surgeon, not photos. Toxicity was judged by the surgeon at the time of each follow-up, using the CTCAE scale, version 4. Median follow-up is 2 years. Results: Two patients were lost to follow-up. There were no in-breast and 1 axillary recurrence. Grade 2 or higher toxicities were seen in 10 patients (7.2%, one of whom had Lupus), and only 1 lasted beyond a year. Toxicity included 1 transient breast edema, 1 late mastitis at one year, 1 grade 4 (0.7%), 0 grade 3, 5 grade 2 (3.6%), and 7 grade 1 fat necrosis, 3 grade 2 fibrosis (2.2%), and only 1 transient arm lymphedema (all patients had SNB). Cosmesis was judged as poor in 1 (0.7%), fair in 2 (1.4%), good in 19 (14%), and excellent in 116 (84%). Pockmarks were visible on casual examination in 8% after one year. Conclusions: Oncoplastic surgery combined with sentinel node mapping and interstitial brachytherapy has resulted in low toxicity (7.2%) and high rates of acceptable cosmesis (98% good/excellent), as scored by a single surgeon with strict criteria at each follow-up visit. No conclusions about tumor control will be made until this cohort has mature follow-up.
Abstract 15379: Prognostic Impact of Arterial Carbon Dioxide Levels in Patients With Acute Decompensated Heart Failure
Authors: Takao Kato, Takatoshi Kasai, Shoko Suda, Ayako Onodera, Masaru Hiki, Tetsuro Miyazaki, Atsutoshi Takagi, Katsumi Miyauchi, Hiroyuki Daida
Journal: Circulation (2013)

Background: Although assessing arterial blood gas (ABG) is recommended, prognostic values of arterial carbon dioxide (CO2) levels in patients with acute decompensated heart failure (ADHF) are not w...
Concept and feasibility of the randomized comparison of imatinib with imatinib combination therapies for chronic myeloid leukemia: The German CML Study IV - Pilot Phase
Authors: R. Hehlmann, A. Hochhaus, U. Berger, M. Pfirrmann, J. Hasford
Journal: Journal of Clinical Oncology (2005)

6574 Background: Chronic myeloid leukemia (CML) is considered a clinical model for other neoplastic diseases. Targeted therapy with the BCR-ABL tyrosine kinase inhibitor imatinib (IM) induces high response rates in CML. Nevertheless, residual disease remains in virtually all patients (pts) on IM monotherapy as a potential cause of relapse. Methods: In July 2002, a randomized trial has been activated comparing IM 400 mg/d with IM+IFN, IM+Ara-C, and IM after IFN failure (or 800 mg IM monotherapy in high risk pts) in newly diagnosed CML. The study is accompanied by a comprehensive cytogenetic and molecular surveillance program to monitor response and to search for early signs of relapse. Results: By 12/2004, 505 pts were randomized. 35% were low, 54% intermediate, and 11% high risk according to the Euro score. A cohort of pts (n=279) recruited by 9/03 with a >12 months follow up was evaluated. Cytogenetic data were available from 161/222 pts (73%) randomized to IM based therapies. At 12 months, 142 pts (64%) achieved a major cytogenetic response (Ph+<35%), being complete in 53%. Quantitative PCR data were available in 182 pts (82%). 58 pts (26%) achieved a major molecular response (ratio BCR-ABL/ABL <0.12%). In one patient (0.5%) BCR-ABL became undetectable. 5/116 pts lost CCR (4%) during the first year. 9/222 pts (4 low, 2 intermediate, 3 high risk; 4%) progressed to blast crisis, 4 of them showed clonal evolution (complex aberrant karyotype, n=3; +8, n=1), 2 others BCR-ABL mutations (K247R and E355G). IM therapy was stopped due to side effects or resistance in 6% of pts in the IM 400 mg arm, 2% in the IM+IFN arm, and 4% in the IM+Ara-C arm. IFN was stopped in 21%, Ara-C in 13% of pts. Conclusions: The pilot phase of CML IV has proven feasibility of IM combinations in addition to high response rates. Long-term observation will demonstrate whether the promising results will be maintained and will improve survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Roche
The 50-month results of the four non-platinum concurrent chemoradiation regimens for locally advanced cervical cancer
Authors: P. Kamnerdsupaphon, I. Chitapanarux, V. Sukthomya, V. Lorvidhaya
Journal: Journal of Clinical Oncology (2007)

5540 Objectives: To determine the efficacy, disease free and overall survivals of radiation therapy in combination with four non-platinum chemotherapy regimens for locally advanced cervical cancer. Materials and Methods: Eligible patients were those with a diagnosis of locally advanced cervical cancer, under 70 years of age, and undergone the necessary prestudy investigations. All patients received external-beam pelvic irradiation to a minimum dose of 5,000 cGy, and brachytherapy delivered to bring the minimum total dose at point A to 7,500 cGy. Patients were randomized to receive one of four chemotherapy regimens: Arm1: oral 5FU 250 mg/m 2 /day, Arm2: mitomycin 12 mg/m 2 on days 1 and 28 + oral 5FU 200 mg/m 2 /day, Arm3: mitomycin 12 mg/m 2 on days 1 and 28 followed by 5FU 1,000 mg/m 2 /day on days 1 through 4 and 28 through 31, Arm4: oral hydroxyurea 25 mg/kg/day. Results: From September 1995 to October 2001, the study include 921 women; 226 in arm 1, 229 in arm 2, 234 in arm 3, and 232 in arm 4. The median follow-up time was 51.69 months. More than 89% of the patients achieved complete response. Disease free survival rates were 62.4% among arm 1, 63.8% among arm 2, 66.2% among arm 3, and 68.5% among arm 4. Overall survival rates were 77.4%, 79.5%, 80.8%, and 84.5% respectively. Conclusion: The efficacy of these regimens were not inferior to the standard platinum based regimen for locally advanced cervical cancer. This study demonstrates the results of large randomized clinical study of radiochemotherapy and requires the longer follow up time for the late complications. No significant financial relationships to disclose.
Treatment of high-risk MDS patients (pts) with -7/del(7q) with azacitidine (AZA) versus conventional care regimens (CCR): Effects on overall survival (OS)
Authors: G. J. Mufti, P. Fenaux, E. Hellstrom-Lindberg, V. Santini, A. F. List, S. Gore, J. F. Seymour, L. R. Silverman, J. Backstrom, C. L. Beach
Journal: Journal of Clinical Oncology (2008)

7033 Background: -7/del(7q) is associated with poor prognosis in MDS. In a recent phase III, randomized trial, AZA significantly prolonged OS in pts with high-risk MDS (Fenaux, Blood 2007;110,817). This analysis assessed the effect of AZA on OS in this subgroup of high- risk MDS pts with -7/del(7q). Methods: Primary inclusion criterion for the Phase III study was high-risk MDS (FAB RAEB, RAEB-T, or CMMoL and IPSS Int-2 or High). Pts were randomized to AZA (75 mg/m2/d x 7d, q28d) or CCR. CCR comprised 3 treatments: BSC only (transfusions, antibiotics, G-CSF for neutropenic infection); low-dose ara-C (20 mg/m2/d x 14d, q28d); or induction chemotherapy (7+3 regimen). No erythropoietin was allowed. Results: At baseline (BL), 57 (30 AZA, 27 CCR) of 358 pts in the total population had -7/del(7q), 35% had -7/del(7q) alone and 65% had -7del(7q) as part of complex karyotype. BL characteristics were balanced in the 2 arms: 70% male; median age, 69 years. The median Kaplan Meier difference in OS for AZA vs CCR was 8.4 months, a significant improvement (3-fold) over CCR (Table). The hazard ratio (HR) was 0.33 (95% CI: 0.16–0.68) indicating a 67% reduced risk of death in the AZA arm; this compares with an HR of 0.58 for the OS improvement with AZA vs CCR with all cytogenetic subtypes in the phase III trial. At 2 years, a 4-fold OS advantage was observed in the AZA arm with 33% of pts alive vs 8% in the CCR arm (p=0.03). Secondary endpoints support the OS advantage (Table). Significantly higher IWG 2000 response rates (CR+PR) were seen in pts with -7/del(7q) alone (64% vs 11%; p=0.03) or complex (21% vs 0; p=0.02) with AZA vs CCR, and compared favorably to the overall AZA group with IPSS good and intermediate cytogenetics. AZA was generally well tolerated. Conclusion: This phase III subgroup analysis indicates the disease modifying effect of AZA extends to unfavorable cytogenetic patterns that include -7/del(7q), and suggests AZA may represent the treatment of choice for this otherwise poor prognosis subset. OS, CR, PR, HI, and transfusion independence (TI) in RBC-dependent -7/del(7q) pts at BL (n/N,%) OS (mos) CR+PR CR RBC TI HI-E HI-P AZA 13.1 13/30, 43 8/30, 27 12/21, 57 13/26, 50 10/20, 50 CCR 4.6 1/27, 4 1/27, 4 0/19, 0 0/24, 0 2/25, 8 P value 0.003 0.0005 0.03 <0.0001 <0.0001 0.002 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pharmion Amgen, Celgene, Pharmion Corporation Pharmion Amgen, Celgene, Cephalon, Johnson & Johnson, Novartis, Pharmion, Roche Pharmion Corporation
A randomized, placebo-controlled, multicenter phase II adjuvant trial of the efficacy, immunogenicity, and safety of GI-4000 plus gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer with activating ras mutations.
Authors: S. H. Whiting, P. Muscarella, A. Rosemurgy, W. E. Fisher, D. A. Richards, F. E. Harrell, J. Ferraro, S. Speyer, A. Cohn
Journal: Journal of Clinical Oncology (2010)

TPS226 Background: Patients with resected pancreas cancer treated with standard of care gemcitabine (Gem) have a median recurrence-free survival of 14 months, median overall survival of 22 months, and a survival rate of 20% at 5 years. The postresection patient population represents a compelling model of minimal residual disease for which targeted and active immunotherapy may decrease cancer recurrence and improve survival through elimination of microscopic disease. Activating mutations in ras occur early in the development of pancreas cancer and are subsequently maintained, being found in > 90% of pancreas cancer cases. This trial is designed to evaluate the efficacy, immunogenicity, and safety of GI-4000 plus Gem versus placebo plus Gem in patients with resected pancreas cancer and an activating ras mutation. GI-4000 is a proprietary immunotherapy designed to target cells with activating ras mutations using whole, heat-killed recombinant Saccharomyces cerevisiae yeast (called Tarmogens = targeted molecular immunogens). Tarmogens have demonstrated selective killing of target cells expressing a number of cancer antigens including mutated ras in vivo by activating an antigen-specific T cell mediated response. Methods: The study population consists of subjects with pancreas cancer who have an activating mutation in ras and an R0 or R1 resection by the Whipple procedure. Subjects are randomized to either GI-4000 plus Gem or placebo plus Gem; 3 weekly injections of GI-4000 40YU (or placebo) are followed by 6 cycles of Gem 1000 mg/m2 iv infusion (day 1, 8, 15 every 28 days). Monthly doses of GI-4000 or placebo are administered on the Gem off-weeks and continue monthly for up to 5 years or until subjects experience intolerance, disease recurrence, or death. This trial uses a Bayesian statistical approach to analyze efficacy on a quarterly basis using time to recurrence as the primary efficacy endpoint and time to mortality as a key secondary efficacy endpoint. Enrollment is ongoing and may continue up to 200 subjects based on pre-specified treatment effects observed for RFS and OS. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlobeImmune Amgen, Bristol-Myers Squibb, Daiichi Sankyo, Seattle Genetics GlobeImmune Amgen, Bristol-Myers Squibb, Novartis, sanofi-aventis GlobeImmune, sanofi-aventis
P80 Antiviral therapy in HCV cirrhotic patients: early on-treatment haematological parameters and genotype predict response
Authors: I Carey, A Mendes, D Joshi, A Gera, M Al-Freah, S Knighton, A Suddle, K Agarwal
Journal: Gut (2010)

Introduction  Pegylated interferon-a (Peg-IFN)+ribavirin (Riba) is standard of care for treatment of chronic hepatitis C (CH-C). Antiviral therapy is recommended in those with compensated disease and lower rates of treatment responses are noted with little data on predictors of outcome in this “difficult to treat” group.  Aim  To assess pre-treatment, on treatment haematological, biochemical and clinical characteristics of patients with CH-C cirrhosis and response to antiviral therapy in a single centre cohort.  Method  66 patients with CH-C infection and cirrhosis (96% Child-Pugh A, median MELD 13 and UKELD 44), median age 51 years (range 21–70), 50 males; treated with Peg-IFN 2a and weight based Riba (13 mg/kg/day) according to their genotype (24–72 weeks) between July 2006 and December 2009. Patients were divided into 3 groups by response: sustained responders (SVR) n=20 (30%), relapsers (Rel) n=24 (37%) and non-responders (NR) n=22 (33%). Virological, biochemical and haematological parameters (HCV RNA viral load, HCV genotype (G), sodium, bilirubin, creatinine and albumin levels, prothrombin time, haemoglobin (Hb) levels and neutrophil (ANC), platelets (PLT) counts were assessed at baseline (W0) and at different timepoints: treatment week 4 (TW4), TW8, TW12, TW24 (G1&4) and at the end of therapy (EOT). Child-Pugh, MELD and UKELD scores were assessed and compared with outcome.  Results  Baseline HCV RNA viral load was similar in SVR, Rel and NR. SVR was significantly lower (13% vs 54%, p  Conclusion  Antiviral therapy in our population was safe. Early decrease in Hb at W12 (perhaps reflecting inter-individual ribavirin concentration); HCV genotype, higher baseline ANC and PLT counts were associated with response.
Remission induction of meningeal leukemia with high-dose intravenous methotrexate.
Authors: F M Balis, J L Savitch, W A Bleyer, G H Reaman, D G Poplack
Journal: Journal of Clinical Oncology (1985)

Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.