tbuckley/cabot-search huggingface dataset:
Performance and side effect evaluation of sequentially reduced radiotherapy doses in a phase II trial of induction chemotherapy (IndCT) followed by concomitant chemoradiotherapy (CTX) for advanced head and neck cancer (HNC)
Authors: M. A. List, E. E. Vokes, E. W. Cohen, K. M. Stenson, T. Karrison, B. E. Bruce, M. Witt, D. J. Haraf
Journal: Journal of Clinical Oncology (2006)

5558 Background: CTX regimens are often limited by severe acute toxicities and long-term functional impairment. This paper presents patient (pt) reported side effects and performance outcome in 3 sequential groups of stage IV HNC pts treated at the University of Chicago with IndCT and lowering radiation doses with the goal of maintaining survival while minimizing negative sequelae. Methods: Pts. were treated with IndCT followed by alternating weeks of concurrent CTX with lowering doses of radiotherapy to gross disease/ high risk microscopic/low risk microscopic disease: Group A - 75/60/45 Gy (n = 36 pts); Group B - 75/54/39 Gy (n = 34 pts); Group C - 72/51/36 Gy (n = 60 pts), respectively (treatment details &amp; survival analyses presented separately). Pts were assessed for quality of life, performance (Performance Status Scale for HNC) and side effects (Radiotherapy Questionnaire) pretreatment, during CTX, at 3 &amp; 12 months and annually thereafter. Controlling for baseline scores, differences between the groups were examined on- treatment and at 12-months. Results: Baseline and 12-month data were available for 81/114 pts. While all pts declined in performance (e.g., diet) and reported increased side effects (e.g., dry mouth, mouth pain, swallowing problems) on CTX, there were no statistically significant differences based on radiation dose. Similarly, there was improvement in most symptoms by 12 months with little difference among groups. In contrast, on normalcy of diet, fewer patients in Group C (20%) showed declines of more than 20 points from baseline compared to A (46%; p = .085) and B (45%, p = .09). Overall, 4% of patients were unable to take anything orally at 12-months with no difference among groups. Conclusions: This study showed no differences in pt reported symptoms on-treatment or at 12-months based on lowered radiation doses during CXT. On the other hand, while there continued to be some restriction in long-term diet, pts in the lowest radiation dose group showed somewhat less decline from baseline. These findings suggest the continued need to explore ways of decreasing both acute and long term toxicities in the use of CTX regimens. [Table: see text]
Alkylphosphocholine Perifosine Inhibits Myeloma Cell Growth While Inducing Myeloid Hyperplasia in a Murine Myeloma Model.
Authors: Laurence Catley, Teru Hideshima, Dharminder Chauhan, Paola Neri, Piefrancesco Tassone, Yu-Tzu Tai, Weihua Song, Daniel R. Carrasco, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2005)
A phase II study of intravenous DX-8951f administered daily for five days every three weeks to patients with previously untreated metastatic gastric cancer
Authors: C. R. Becerra, C. Takimoto, J. A. Ajani, P. Major, K. Feit, A. Duggal, R. De Jagger
Journal: Journal of Clinical Oncology (2004)

4126 Background: Exatecan Mesylate (DX-8951f, Daiichi Pharmaceutical Co., Ltd., Japan) was synthesized to impart greater antitumor efficacy and less toxicity than those of existing camptothecin analogues. Methods: The objectives of this study were to determine the anti-tumor activity (RECIST criteria), safety and pharmacokinetic (PK) profile of DX-8951f in patients with previously untreated metastatic gastric cancer. Starting dose of DX-8951f was 0.5 mg/m2/day on days 1–5 of a 3-week course. PK blood samples were collected from each patient during the first course of therapy. Results: 41 patients enrolled; 39 received at least one full course of DX-8951f and were evaluable for safety and efficacy analyses. Median age 61 years (range, 32–81 years), ECOG performance status 0–1 in 34 (87.2%) patients. Metastases sites included liver (61.5%), lymph nodes (46.2%), lung (20.5%), and peritoneum (10.3%). 141 courses of DX-8951f administered (median 3, range 1–10). Six patients required dose reduction (5 due to neutropenia) to 0.4 mg/m2/day while 6 patients met protocol criteria for dose escalation to 0.6 mg/m2/day. Two (5.1%) patients had a partial response (PR); 18 (46.2%) patients had stable disease(SD), including 5 patients with unconfirmed PR. Median time to tumor progression 2.7 months, median survival 6.6 months. CEA decreased by >25% in 7 of 18 patients (2 confirmed partial response,3 unconfirmed partial responses and 2 stable disease). Toxicities neutropenia > anemia > thrombocytopenia with reversible non-cumulative grade 3(35.9%) and 4 (41%) neutropenia. Other mild to moderate toxicities included nausea, vomiting, fatigue and alopecia. There were no drug-related deaths. Conclusion: DX-8951f showed moderate activity in untreated patients with metastatic gastric cancer. The toxicity profile of DX-8951f, mainly myelosupression, was predictable and similar to that observed in other Phase II studies. Future combination studies of DX-8951f with other chemotherapeutic agents may be warranted in patients with metastatic gastric cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi Pharmaceutical Corp. Daiichi Daichii Pharmaceutical Corporation
Comparison of treatment patterns and outcomes in metastatic breast cancer (MBC) patients initiated on trastuzumab versus lapatinib: A retrospective analysis.
Authors: Genevieve Gauthier, Annie Guerin, Amy Styles, Eric Q. Wu, Melissa G. Brammer, Deepa Lalla
Journal: Journal of Clinical Oncology (2012)

e11076 Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend trastuzumab- or lapatinib-based therapies as the preferred agents for metastatic HER2-positive breast cancer. Few studies have compared treatment patterns and outcomes in MBC patients (pts) treated with trastuzumab vs. lapatinib. The objective of this study is to compare rates of new metastatic sites, discontinuation, healthcare resource utilization, and costs in MBC pts initiated on lapatinib vs trastuzumab. Methods: Adult women with MBC initiated on trastuzumab or lapatinib on or after 03/13/2007 (lapatinib FDA-approval date) were selected in the PharMetrics® Integrated Database (2000-2011). Pts were followed from trastuzumab or lapatinib initiation date up to the end of continuous healthcare plan enrollment/data availability, whichever occurred first. New metastatic sites and discontinuation rates (gap ≥45 consecutive days) were compared among trastuzumab and lapatinib pts using multivariate Cox proportional-hazards models. Incremental healthcare resource utilization and monthly costs (2010 USD; measured from a payer perspective) were estimated using multivariate generalized linear models. Results: Among the643 pts selected, 381 and 262 pts were initiated on trastuzumab and lapatinib, respectively. After multivariate adjustment, compared to trastuzumab pts, lapatinib pts had a higher rate of new metastases (hazard ratio [HR]=1.65; p&lt;.001) and treatment discontinuation (HR=1.57; p&lt;.001). There was no statistically significant difference in total healthcare cost between lapatinib and trastuzumab pts (p=.397). The incidence of medical visits associated with treatment administration was lower in lapatinib pts (Incidence rate ratio [IRR]=0.34; p&lt;.001), however, the incidence of other outpatient visits was significantly higher in lapatinib pts (IRR=1.19; p&lt;.001). Conclusions: Whileboth cohorts presented similar healthcare costs, pts initiated on lapatinib showed higher rates of new metastatic sites, discontinuation, more outpatient visits (non treatment-related), but fewer medical visits associated with treatment administration.
Prognostic and predictive values of carbonic anhydrase IX (CAIX) and pathologic features in patients with metastatic clear cell renal cell carcinoma receiving targeted therapy
Authors: T. K. Choueiri, M. Regan, W. Oh, J. Clement, A. Amato, D. McDermott, D. Cho, M. Atkins, S. Signoretti
Journal: Journal of Clinical Oncology (2009)

e16067 Background: Tumor Carbonic Anhydrase IX (CAIX) expression and histologic features can predict outcome in patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy. We sought to investigate the prognostic and predictive utility of such features in patients receiving VEGF-targeted therapy. Methods: We identified 118 patients with mRCC initiating first- line VEGF-targeted therapy including 94 with clinical data, clear cell histology and available tissue. Tumors were evaluated for specific histologic features and for CAIX expression by immunohistochemistry using the MN75 antibody. The relationship between these pathology findings and tumor shrinkage and other treatment outcomes was assessed. Results: Higher tumor clear cell component was independently associated with greater tumor shrinkage (p=0.02), response (p=0.02) and treatment duration (p=0.02). Patients with high vs. low tumor CAIX expression had mean tumor shrinkages of -12% vs. -5%, respectively (p=.38). There was heterogeneity in tumor responsiveness to sunitinib or sorafenib according to CAIX status (p=0.055 for interaction): mean shrinkage was -17% vs. -25% (mean difference +8%, 95% CI -14% to +31%) for sunitinib-treated patients with high vs. low tumor CAIX expression compared to -13% vs. +9% (mean difference -22%, 95% CI -42% to -1%) for sorafenib-treated patients. Conclusions: Patients with higher clear cell component in their tumors are likely to experience superior clinical benefit from VEGF-targeted therapy. Although CAIX expression was not found to be of prognostic value in patients with clear cell mRCC treated with VEGF-targeted therapy, it may be a predictive biomarker for response to sorafenib treatment. [Table: see text]
Racial/ethnic disparities in liver cancer-attributable hepatitis infections in the U.S. population.
Authors: Kevin J. Moore, Erin Dunn, Stacey L. Tannenbaum, Tulay Koru-Sengul
Journal: Journal of Clinical Oncology (2015)

259 Background: According to the American Cancer Association, hepatitisB and Cinfections may raise liver cancer risk. We identify population-specific cancer-attributable hepatitis prevalence to discern disparities across race/ethnicity for liver cancer risk. Methods: Data from 1999-2012 National Health and Nutrition Examination Survey (NHANES) were used to determine prevalence, unadjusted odds ratios (OR) with 95% confidence intervals (95%CI) for non-Hispanic-Whites (NHW), non-Hispanic-Blacks (NHB), Mexican-Americans, other Hispanics, and other race of hepatitis, taking complex sampling design into account. Results: Among those sampled, the overall highest prevalence of hepatitis infection was 66.4% in NHW for hepatitis-C and the lowest prevalence was 1.4% in Mexican-Americans for hepatitis-B surface-antigen. NHB were more likely than NHW to have hepatitis-B infections of surface-antibody (OR=1.9; 95%CI=1.8-2.0), core-antibody (3.3; 3.1-3.6), surface-antigen (5.3; 3.6-7.7), and hepatitis-C infections (1.7; 1.5-2.0). Compared to NHW, other Hispanics had a higher burden of hepatitis-B infection of surface-antibody (1.5; 1.4-1.7) and core-antibody (2.5; 2.1-2.8); other race had the same higher infection pattern as other Hispanics in surface-antibody (2.4; 2.2-2.6) and core-antibody (6.7; 6.0-7.5). Surface-antibody was more prevalent (1.5; 1.4-1.6) while core-antibody was less prevalent (0.9; 0.8-0.9) among Mexican-Americans compared with NHW. Conclusions: The prevalence of hepatitis B and C infections varies across different race/ethnicities with NHB having the greatest burden compared with NHW. Population-based databases should collect more information regarding infection burden in at-risk groups in order to understand more about these disparities. Appreciating such gaps across demographics could assist in future efforts to decrease the burden of hepatitis and to provide a base for targeted liver cancer prevention programs via screening, vaccination, health promotion, and literacy.
Phase II open label trial of imatinib in polycythemia rubra vera
Authors: C. M. Jones
Journal: Journal of Clinical Oncology (2005)

6517 Background: Polycythemia rubra vera (PRV) is a myeloproliferative disorder characterized by panmyelosis. Increased mRNA for c-kit has been demonstrated in CD34+ stem cells in patients with polycythemia vera. Since Imatinib is able to inhibit not only the brc/abl tyrosine kinase but also c-kit, we treated and subsequently reported two patients with PRV who responded to Imatinib with complete remission. Methods: Planned enrollment for this trial was 20 patients. All patients had to meet the PRV study group criteria for enrollment. Patients currently on hydroxyurea were given a week washout before beginning the study. Treatment goals were a hematocrit ≤ 44 or a platelet count ≤ 600,000 after two weeks of treatment. Dose escalation to 600 mg and 800 mg a day was allowed at two week intervals. Imatinib levels were measured in all patients requiring dose escalation. Results: Sixteen patients, 14 Caucasian and 2 African-Americans, patients have been enrolled. The mean time on treatment is 52 weeks. Mean age is 54 years. Male to female ratio is 2:1. Eight patients have experienced GI events with grade 2 toxicity occurring at 600 mg a day and grade 3 diarrhea and one GI bleed occurring at 800 mg a day. One patient experienced grade 1 rash and two grade 1 musculoskeletal symptoms, both at 400 mg a day. Three patients requested removal from study after one week of therapy. One was removed during screening. Twelve patients remain on study and five have achieved a complete remission on 400 mg a day. Seven have required dose escalation with four patients now at 500 mg a day, one at 600 mg a day. Two patients have required 800 mg a day. Both have subsequently required dose reductions for GI adverse events. Three patients required anagrelide at four weeks but only two remain on anagrelide at the time of this report. Two of three patients requiring dose escalation at two weeks have Imatinib levels [856 and 674 ng/ml] below the therapeutic range seen with our CML or GIST patients. This did not reach statistical significance. Conclusion: We believe that Imatinib is an effective treatment in PRV will offer an option for younger patients in whom the risk of hydroxyurea therapy could be unacceptable. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Complex urological oncological surgeries can be performed using minimally invasive robotic or laparoscopic methods with similar perioperative results compared to conventional open methods
Authors: K. C. Balaji, L. Smith, T. Nazemi
Journal: Journal of Clinical Oncology (2005)

6104 Background: Robotic and laparoscopic surgical methods (RLM) are being increasingly used to perform complex urological oncological procedures. We compared the perioperative outcomes in a cohort of patients undergoing complex urological oncological surgeries by either RLM or open methods (OM) by a single surgeon, thereby minimizing the impact on perioperative outcome of different surgeons performing the procedure. Methods: The relevant data on 203 consecutive patients over the last 4-year period was entered in to Microsoft Access database and queried. Continuous variables were compared using the Wilcoxon rank sum test and categorical variables were compared using Fisher’s exact test to a significance level of p value < 0.05. Results: Of the 203 patients who underwent complex urological oncology surgeries, OM and RLM was used in 115 (57%) and 88 (43%) of patients respectively. The age, sex and body mass index between the 2 groups were comparable. Four perioperative mortalities (2%) occurred, with 3 in OM and 1 in RLM group. A total of 34 (17%) perioperative complications occurred in the entire cohort with 16 (14%) occurring in the OM group compared to 18 (20.5%) in the RLM group. Radical prostatectomy, radical cystectomy, radical or partial nephrectomy was performed in (OM, RLM) 87 (58, 29), 38 (25, 13), 57 (18, 39) and 21 (14, 7) patients respectively. Within the subgroups undergoing specific surgeries there were no statistical difference in perioperative complication rates, hospital stay, drop in hemoglobin or change in serum creatinine between the OM and RLM (p > 0.05). The operative time was significantly longer in patients undergoing radical prostatectomy by RLM compared to OM (p <0.0001). The estimated blood loss was significantly lower in patients undergoing radical prostatectomy, nephrectomy, and cystectomy by RLM compared to OM (p <0.0001, p = 0.01, p = 0.002), and blood transfusion rate was lower in the RLM prostatectomy group compared to the OM (p = 0.025). Conclusions: Complex urological oncological procedures can be performed without significantly increased perioperative complications by RLM compared to OM. No significant financial relationships to disclose.
Neuropathy with docetaxel (DC) and paclitaxel (PC) in adjuvant breast cancer (BC) in a U.S.-managed care database.
Authors: J. P. Burke, B. S. Seal, A. H. Teitelbaum, H. J. Henk
Journal: Journal of Clinical Oncology (2010)

e11042 Background: Side effects of taxanes are well documented and neuropathy, which can be dose-limiting, may result in treatment modifications. This study examined the occurrence of neuropathy from commercially insured U.S. patients with BC treated with adjuvant DC or generic PC. Methods: This was a retrospective database analysis using eligibility, medical and pharmacy claims data from a large U.S. health care organization. Subjects with a claim for BC and a claim for PC or DC-containing chemotherapy from 1/1/98-12/31/05 were included. Subjects were stratified by dosing interval (weekly [qw] or Q 21 days [q3w]) and had to have at least 1 claim for adjuvant therapy during the 1-year baseline period and evidence of surgery for BC in the 5 months prior to index date. Subjects were followed until the earliest of death date, date of last enrollment or 12/31/06. Chi-square compared descriptive variables. Logistic regression (LR) examined the independent association of index medication and neuropathy. Covariates included age, region, baseline co-morbidity score and use of medications for neuropathy. Results: 3,619 subjects were identified for generic PC (n = 329, qw; 1,685, q3w) or DC (n = 204, qw; 1,045, q3w). A significantly lower frequency of neuropathy was noted in the follow-up period for DC-based treatments compared to generic PC (7.0% vs. 10.6%, p < 0.001). Differences were noted also when stratifying by dosing interval (6.7% vs. 10.0%; p = 0.003 in q3w, 9.3% vs. 13.7%; p = 0.061 in qw). After adjusting for covariates, the odds of neuropathy remained significantly lower with DC-based treatment (OR = 0.70, CI = 0.559, 0.920; p = 0.010). Conclusions: Although grade of neuropathy and neuropathy-related treatment modification could not be assessed in this retrospective review, a lower occurrence of neuropathy was noted with DC-based treatment compared to generic PC. This difference persisted with stratification by dosing interval. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim
Clinical outcomes in pancreatic adenocarcinoma (PAC) in breast cancer (BC) survivors.
Authors: M. A. Lowery, Z. K. Stadler, E. Ludwig Miller, D. R. D'Adamo, E. Salo-Mullen, P. Allen, R. C. Kurtz, D. P. Kelsen, E. M. O'Reilly
Journal: Journal of Clinical Oncology (2010)

4152 Background: PAC in BC survivors is rare (Andersson, Acta Oncologica, 2008, 47:755-764) and may occur as part of an inherited cancer predisposition syndrome. Up to 10% of PAC patients (pts) have an inherited form of the disease with germline mutations (m) in BRCA1 and BRCA2 representing a portion of this group (Lynch, Pancreatology, 2001. 1:466-471). PALB2 has recently been identified as a susceptibility gene for both BC and PAC (Jones, Science, 2009, Apr 10; 324:217). Clinical outcomes in BC survivors who develop PAC have not been previously described. Methods: 30 pts with a personal history of BC and PAC were identified from the MSKCC Pancreatic Cancer Family Registry; 13 pts (43%) were Jewish. Two pts had undergone testing for BRCA m, both negative. Six other pts with BRCA2 m and PAC (1 male) and one pt with BRCA1 m and PAC, were also identified. Results: Of 30 pts with BC and PAC, median age at diagnosis of PAC and BC was 66.5 years (yrs) and 61 yrs, respectively. Median interval between diagnosis of BC and PAC was 7.5 yrs. Eight (27%) pts had a first-degree relative (FDR) with BC; 6 (20%) pts had a FDR with colon cancer; and 2(7%) had a FDR with PAC (Table). Conclusions: OS in BC survivors with PAC appears greater than predicted for all stages of disease. In pts with a personal history of BC and PC, genetic testing for germline m in BRCA1 and BRCA2 as well as consideration of PALB2 testing is appropriate. Further genetic characterization of this group may help to influence treatment choices and guide prognosis. The use of platinum therapy, RT, and more recently PARP inhibitors to target the BRCA-associated defective DNA repair mechanism, are deserving of further evaluation in pts with BRCA associated PAC. BC and PAC (n=30) BRCA and PAC (n=7) Median age at diagnosis 66.5 yrs 60 yrs OS resected 53.3 months (mo) (n=10) 1 pt deceased 19.2 mo 2 pts alive at 27.2 and 2.3 mo post op OS locally advanced (LA) 24.2 mo (n=7) 2 pts alive at 9.8 and 8.7 mo OS metastatic (M1) 11.4 mo (n=13) 18.3 mo (n=2) # of pts receiving platinum chemo for LA or M1 PAC n=10 (of 27) n= 4 (of 6)* # of pts receiving radiotherapy (RT) for LA PAC n=5 (of 7)** n= 2 * 1 pt achieved CR. ** 1 pt had subsequent R0 resection. No significant financial relationships to disclose.