tbuckley/cabot-search huggingface dataset:
Evaluation of a protocol algorithm for the treatment of epidermal growth factor receptor inhibitors-induced dermatological side effects (EPIDERM Study)
Authors: M. Pilon, M. Mailhot, A. Comtois, D. Soulieres, D. Charpentier, N. Letarte, Y. Moride
Journal: Journal of Clinical Oncology (2008)

20755 Background: Epidermal growth factor receptor inhibitors (EGFRIs) are emergent targeted therapy agents used in various malignancies. These drugs are associated with dermatological toxicities for which no specific treatment guidelines are yet defined. Methods: The EPIDERM study evaluated the impact of a standardized protocol of intervention for active treatment of early stages of the EGFRIs-induced skin rash. We conducted a comparative study of historical controls with a prospective group of patients receiving EGFRIs, and receiving treatment according to an algorithm. This algorithm consisted of a predetermined treatment schema (topical and p.o. corticosteroids, topical and p.o. antimicrobials and lotion according to the toxicity grade. The study end-points were the rates of resolution and improvement of the rash and the rates of discontinuation, interruption and dose reduction of the EGFRIs with or without the treatment algorithm. Analysis were made with a log-rank test. All patients receiving EGFRIs were illegible to enter the study. Results: 59 patients were included in the study (44 historical controls and 15 prospective patients) between May 2006 and April 2007. Most of them (99%) received erlotinib or cetuximab and were treated for lung or head and neck cancer. We observed an incidence of rash of 83% in the historic group and 75% in the prospective group. These patients showed a better evolution (improvement and resolution) of the rash (p = 0,025), and a reduction of dose modification of the EGFRIs treatment because of the rash (p= 0,041). No patient discontinued EGFRIs in the prospective group. Conclusions: This study shows that an early and standardized intervention to treat the EGFRIs-induced skin rash has a positive impact on the patient and its cancer treatment. The EPIDERM protocol treats the skin toxicity and helps the patients to continue on with their planned treatment. These findings may help to propose guidelines to treat these very frequent side effects. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche
Results from a randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy (REASON).
Authors: C. Lhomme, D. Berton-Rigaud, F. Joly, J. Baurain, F. Rolland, A. Stenzl, T. Schmelter, M. Campone
Journal: Journal of Clinical Oncology (2011)

9116 Background: Sagopilone, a novel, fully synthetic epothilone, has shown significant activity in a broad range of preclinical tumor models and in phase II studies in ovarian cancer (OC) and castrate-refractory prostate cancer (CRPC). Peripheral neuropathy (PN) is the most clinically relevant toxicity of sagopilone. Several studies have suggested that acetyl-L-carnitine (ALC) may prevent chemotherapy-induced PN. The REASON study is the first randomized, prospective, placebo-controlled study to investigate the safety, efficacy, and pharmacokinetics of sagopilone plus ALC for the prevention of sagopilone-induced PN. Methods: Patients (pts) with advanced refractory or relapsed OC or CRPC and no evidence of neuropathy received sagopilone (16 mg/m2 i.v. over 3 h every 3 wk) with either ALC (1,000 mg p.o. 3 times a day) or placebo (PBO) for ≤6 cycles until 1 month after the last sagopilone infusion. Primary endpoint was the incidence of PN determined by pt and investigator assessment; electromyography was performed if grade 2 PN occurred. Results: From August 2008, 150 pts were enrolled over 11 months (98 with OC, 52 with PC; 75 pts ALC, 75 pts PBO). Evaluable pts received ≥1 treatment cycle (n=121). Median duration of treatment (4 cycles, ALC; 5 cycles, PBO) and overall incidence of PN were similar between treatment groups. Incidence of high-grade PN was lower in the ALC group in both tumor types and statistically lower in OC pts (p=0.04). PN onset occurred within the first treatment cycle for 60% of ALC and 52% of PBO pts, with a similar median duration (grades 1-4 PN: 184 days, ALC; 191 days, PBO). There was no notable difference in discontinuations due to adverse events between the 2 groups (20 ALC, 23 PBO). Conclusions: No significant difference in overall PN incidence was observed between treatment groups. However, in OC pts the incidence of high-grade PN was significantly lower in the ALC group compared with the PBO group. PN incidence (%) Pts Treatment All grades G1 G2 G3 G4 Evaluable pts (n=121) ALC 81.0 25.9 36.2 19.0 0 PBO 84.1 22.2 27.0 33.3 1.6 OC (n=82) ALC 77.5 22.5 35.0 20.0 0 PBO 85.7 26.2 19.0 38.1 2.4 CRPC (n=39) ALC 88.9 33.3 38.9 16.7 0 PBO 81.0 14.3 42.9 23.8 0
Cost differences among treatment options for patients with refractory myeloma previously treated with high-dose chemotherapy and autologous stem-cell transplantation: An analysis from the U.S. and Swiss perspectives.
Authors: P. R. Blank, R. Levin, B. C. Pestalozzi, T. D. Szucs
Journal: Journal of Clinical Oncology (2011)

e16569 Background: The introduction of novel agents has significantly improved clinical outcome for myeloma patients. While thalidomide, lenalidomide and bortezomib as well as autologous stem-cell transplantation (auto-SCT) have improved overall survival significantly, they have also enhanced health care costs considerably. Methods: Various combination regimens used for refractory myeloma patients with previous exposure to novel agents (thalidomide, lenalidomide, or bortezomib) with auto-SCT were identified from published phase I or phase II trials. Treatment dosages described in the study protocols and overall response rates (ORR) have been abstracted. Costs have been assessed from the Swiss (CH) and US third-party perspectives. The objective of this cost-analysis was to assess the treatment costs per ORR of different combination therapies in relapsed myeloma patients. Exchange rate CHF 1.0 = USD 1.1 (Jan 2011). Results: Eighteen different treatment options including lenalidomide, bortezomib, thalidomide, doxorubicin, pegylated liposomal doxorubicin (PLD), vincristine, cyclophosphamide, dexamethasone, prednisone or mephalan were assessed. Overall response rates (ORR) in these studies ranged from 39% to 92%. Costs per treatment week (7 days) varied considerably (US: USD 766 - USD 4’940; CH: USD 1’375 - USD 3’699). Accordingly, the weekly costs per ORR yielded results from USD 957 (bortezomib, dexamethasone, doxorubicin) up to USD 8’821 (bortezomib, mephalan, prednisone, thalidomide) in the US. From the Swiss perspective weekly costs per ORR ranged between USD 1’894 (bortezomib, dexamethason, doxorubicin) and USD 9’485 (lenalidomide, bortezomib, dexamethasone). Conclusions: According to our study, costs for refractory myeloma patients vary considerably for the various treatment regimens, especially when ORRs are taken into account. Analyses of drug costs provide important information for clinicians, patients, and health policy makers involved in treatment decisions.
Gender differences in colorectal cancer in downtown Brooklyn, New York.
Authors: Z. M. Bo, K. Veerabhadrappa, K. T. Lyar, R. Sultana, G. M. Villani
Journal: Journal of Clinical Oncology (2011)

e12002 Background: Colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States. CRC is more common in males than in females. Surveillance, Epidemiology and End Results (SEER) incidence for 2003-2007 showed 55.8 per 100000 male colorectal cancers versus 41.7 colorectal cancers per 100000 females. However, tumor registry data from our hospital for the year 2008 showed a female predominance in colorectal cancer incidence. The objective of this study was to evaluate the trends in colorectal cancer incidence, age and stage at initial presentation in a community hospital over a period of five years, with a special emphasis on gender difference in CRC. Ethnicity, median age at diagnosis and stage of the disease at the time of diagnosis is also examined. Methods: A retrospective review of all colorectal cancers diagnosed at the Brooklyn Hospital Center over a five-year period was undertaken. Information regarding gender, race, age and stage at diagnosis was analyzed. Results: Of the 403 patients with colorectal cancer, 323 patients (80.14%) were African American. Of these, 163 patients (40.4 %) were males and 240 patients (59.6 %) were females. Distant metastatic disease at presentation was seen in 19% of the patients and majorities (74%) were older than 60 years. Conclusions: Contrary to SEER data, fewer men than women were diagnosed with colorectal cancer at our institution. In general, studies have shown that women tend to receive CRC screening test less often than men. It is possible that CRC screening uptake may have been even lower in underserved Brooklyn female population. We postulate that these differences signify inadequate and ineffective screening for CRC in women living in Brooklyn rather than a true biologic trend. Until definitive data regarding gender difference in minorities are available, our data supports aggressive screening programs geared towards females, especially among minority population. More studies are needed examining gender differences to identify subgroup population who consistently underuse CRC screening for future interventions.
Survivorship care in Canadian genitourinary oncology: Toward a multidisciplinary perspective.
Authors: Sue Richter, Ashraf AlMatar, Nafisha Lalani, Jackie Bender, David Wiljer, Laura Legere, Christine Massey, Nour Alkazaz, Majula Maganti, Pamela Catton, Srikala S. Sridhar, Michael A. Jewett
Journal: Journal of Clinical Oncology (2013)

337 Background: Genitourinary (GU) cancer survivors comprise nearly 25% of cancer survivors and &gt;50% of all male survivors. To further improve care of this patient population, we need to better understand physician specialist perceptions of survivorship care. Methods: All medical oncologists, urologists and radiation oncologists treating GU cancers in Canada were surveyed with a web−based questionnaire. A total of 27 multiple choice and Likert scale questions were developed in 5 domains: i) demographics, ii) current post cancer treatment care practices, iii) perceived barriers, iv) accessibility to survivorship resources and v) perceptions of advocacy groups. Participants were identified through their respective professional associations. Results: There were 306 responses and 260 were eligible for analysis; 45 medical oncologists, 125 urologists and 90 radiation oncologists. A total of 56% of physicians discharged GU cancer survivor follow-up care to a primary care practitioner (PCP) at some point after treatment. Compared to urologists and radiation oncologists, medical oncologists were least likely to share care with a PCP (4%). Only 47% of all physicians consistently provided a written follow up plan to the PCP and only 25% of these provided lifestyle recommendations. Lack of time and resources were the most commonly reported barriers. About half of physicians reported access to cancer rehabilitation programs as difficult and British Columbia was the most frequently cited region without access. Medical oncologists compared to other subspecialties accessed genetic counseling more easily while access to pain management programs was cited as the most difficult. In general, physicians in community hospitals had the most difficulties. Utilization of advocacy groups was limited, e.g. 23% for prostate cancer. The most underutilized advocacy group was for testis cancer (4%). Conclusions: To our knowledge this is the first study to address the challenges of GU cancer survivorship care in Canada. The barriers to care and underutilization of advocacy groups quoted in this study may be used to stimulate nationwide initiatives to further long-term strategies in GU survivorship management planning.
Phase I first-in-human study of s-<i>trans</i>, <i>trans</i>-farnesylthiosalicylic acid (salirasib) in patients with solid tumors
Authors: A. M. Tsimberidou, M. A. Rudek, D. S. Hong, C. S. Ng, J. Blair, H. Goldsweig, R. Kurzrock
Journal: Journal of Clinical Oncology (2008)

3536 Introduction: S-trans, trans-farnesylthiosalicylic acid (FTS, salirasib) is an oral synthetic small molecule with potent inhibitory properties against oncogenic Ras, which is involved in cell growth, differentiation, and survival in many human tumors. We conducted a phase 1 trial of salirasib in solid tumors. Methods: Salirasib was administered orally for 21D q. 28D. Doses were escalated from 100 to 200, 400, 600, and 800 mg BID. Pharmacokinetic (PK) studies were performed during the first cycle. Results: Twenty-four patients (pts.) were treated. The median age was 56 yrs. (range, 26–76); and 54% were women. Diagnoses were metastatic colon cancer (n=5); appendiceal carcinoma (n=3); pancreatic cancer (n=2); type 2 neurofibromatosis (NF2)-associated tumors (n=2); carcinoid tumors (n=2); osteosarcoma (n=1); ocular melanoma (n=1); and other cancers (n=8). ECOG performance status was 1 in 92% and 0 in 8% of pts. The median number of prior therapies was 3. Eighty-eight cycles were administered (median, 2; range, 1–13+). The most common toxicity was dose-related diarrhea (G1, 54% of pts.; G2, 25%), which was controlled with antidiarrheal agents. Other toxicities included abdominal pain (21% of pts.), nausea, vomiting, and fatigue (17%, respectively). No G3–4 toxicity was noted; and 19 (79%) pts. had no drug-related toxicity >G1. Classic dose-limiting toxicity was not reached, but all 3 pts. treated with 800 mg BID experienced prolonged G1–2 diarrhea, and it was felt that further dose escalation would not be tolerable. Seven (29%) pts. had stable disease (SD) on salirasib therapy for ≥4 months (range, 4–13+) (metastatic carcinoid tumor, n=2; NF2-associated tumors, n=2; myoepithelial cancer of lacrimal gland, n=1; thyroid medullary carcinoma, n=1; and breast cancer, n=1). The median half-life of salirasib was 3.6±2.2 and 2.1±0.9 hours (mean ± SD) on D1 and D15, respectively. PK results were linear with respect to Cmax and AUC across the dose levels studied. There was no difference in PK parameters between single- and multiple-dose salirasib. Conclusion: Salirasib therapy was well tolerated at doses up to 800 mg BID with the major adverse event being dose-related diarrhea. Seven (29%) pts. had SD for ≥4 months. The recommended dose for phase II studies is 800 mg BID. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Averion International Corp Averion International Corp. Concordia Pharmaceuticals, Inc Concordia Pharmaceuticals, Inc
Association of serum B7-H1 level and lymphopenia in diffuse large B-cell non-Hodgkin lymphoma.
Authors: R. A. Wilcox, X. Frigola Baro, L. F. Porrata, E. D. Kwon, M. J. Maurer, I. N. Micallef, T. E. Witzig, S. M. Ansell
Journal: Journal of Clinical Oncology (2010)

8080 Background: Activation of the adaptive immune response plays an important role in tumor immune surveillance. Not surprisingly then, lymphopenia has emerged as an adverse prognostic factor in non-Hodgkin lymphoma (NHL). The factors which may contribute to the development of lymphopenia in NHL are incompletely understood. B7-H1, a member of the B7 family of costimulatory/coinhibitory ligands, inhibits T-cell proliferation and promotes the induction of cell death in tumor-specific T cells. We recently described its expression on malignant cells, tumor-infiltrating dendritic cells, and circulating CD14+HLA-DRlo myeloid-derived suppressor cells in NHL (Blood. 2009;114(10): 2149- 58.). Therefore, we have hypothesized that B7-H1 may contribute to the development of lymphopenia in NHL. Methods: Serum samples were collected from normal donors (n=25) and patients with cutaneous T-cell NHL (CTCL, n=24), peripheral T-cell NHL (PTCL, n=29) and diffuse large B-cell lymphoma (DLBCL, n=31) and levels of soluble B7-H1 (sB7-H1) determined by ELISA. Results: Soluble B7-H1 was detected in serum of both normal donors (mean 0.29 ng/mL; 0.09-0.50 95% CI) and CTCL patients (mean 0.44 ng/mL; 0.25-0.63 95% CI), but was found to be significantly elevated in both PTCL (mean 0.84 ng/mL, 0.49-1.20 95% CI, p<0.001) and DLBCL (mean 0.62 ng/mL, 0.49-0.75 95% CI, p<0.001), when compared with that observed in normal donors. In order to determinewhether sB7-H1 may be associated with the development of lymphopenia, sB7-H1 levels at diagnosis were correlated with matched absolute lymphocyte counts (ALC) obtained from DLBCL patients (n=31). An inverse correlation was noted between sB7-H1 and the ALC. Forty-two percent of patients with elevated sB7-H1 (defined as greater than the mean sB7-H1) were lymphopenic (ALC <900/uL) at diagnosis, whereas 16% of the remaining patients were lymphopenic at diagnosis (p=0.1). Following therapy with anthracycline-based chemotherapy, a 39% reduction in sB7-H1 was observed (n=29, p<0.00001, paired t-test) and was associated with an 18% increase in the ALC. Conclusions: Collectively, the data presented demonstrates that sB7-H1 may represent a novel biomarker in NHL that's associated with lymphopenia. No significant financial relationships to disclose.
An investigation of the role of irinotecan and oxaliplatin in liver toxicity during first-line neoadjuvant chemotherapy.
Authors: Marie Desjardin, Benjamin Bonhomme, Isabelle Soubeyran, Jeremy Vara, Marianne Fonck, Yves Becouarn, Gregoire Desolneux, Veronique Brouste, Serge Evrard, Dominique Bechade
Journal: Journal of Clinical Oncology (2015)

689 Background: Neoadjuvant chemotherapy (CT) have been associated with an increased risk of surgery for colorectal liver metastases (CRLM). Irinotecan (IRI) is claimed to induce CT-associated steatohepatitis (CASH) and oxaliplatin (OX) to induce sinusoidal obstruction (SOS). Imputability is sometimes difficult to establish and the impact on postoperative complications is unclear. The objective of this study is to investigate the impact of IRI and OX on induced liver toxicity, and to study the effects of toxicity on surgical outcomes. Methods: Patients (Pts) who received only one line of CT before resection of CRLM were retrospectively included. CASH and SOS were described according to Kleiner and Rubbia-Brandt classifications respectively. Associations were sought between CASH or SOS and various patient and treatment factors, and between patient and treatment factors and the occurrence of post-operative complications grade 3 or over. Results: Among 379 pts operated on for CRLM from 2003 to 2013, 223 were eligible for inclusion; 57 were excluded as there was no healthy hepatic parenchyma to be analyzed. Median age was 64 y [34-88], BMI ≥25 kg/m² for 52%, 8% had diabetes, and 28% had a dyslipidemia. CRLM were synchronous in 76.5%. 65 (39.2%) received Folfox, 95 (57.2%) Folfiri and 6 (3.6%) Folfirinox. Bevacizumab, cetuximab and panitumumab were given in 71 (42.8%), 30 (17.5%), 4 (2.4%) respectively. Extra-hepatic resections were performed in 78 pts (47%). 90-day mortality was 1.8% and 31 pts encountered complications more severe than 3A. Histological hepatoxicity was established for 82 pts (49%) including 33 (19.9%) with grade 2 or 3 SOS and 22 (13%) with CASH. No significant associations were identified between SOS and OX, nor CASH and IRI. BMI ≥ 25 kg/m² was correlated with an increased risk of CASH. Only septic extra-hepatic surgeries were correlated with the prediction of postoperative complications. Conclusions: In this selected series, preoperative CT was not associated to liver toxicity. The presence of histological lesions did not worsen post-operative outcomes. BMI and extra-hepatic surgery were the only co-factors correlated with CASH and post-operative complications respectively.
Post-treatment prognostic model for patients (pts) with metastatic urothelial cancer (UC) treated with first-line chemotherapy.
Authors: Matt D. Galsky, Erin L. Moshier, Susanne Krege, Chia-Chi Lin, Noah M. Hahn, Thorsten Ecke, Guru Sonpavde, Gregory Russell Pond, James H. Godbold, William K. Oh, Aristotelis Bamias
Journal: Journal of Clinical Oncology (2013)

256 Background: Models to predict the outcome of pts with metastatic UC, based on pre-treatment variables, have previously been developed. However, pts often request “updated” prognostic estimates based on their response to treatment. This is particularly relevant in first-line treatment of metastatic UC, a disease state for which a fixed number of cycles of chemotherapy are typically administered. Methods: Data were pooled from 317 pts enrolled on eight trials evaluating first-line cisplatin-based chemotherapy in metastatic UC. Variables were combined in a Cox proportional hazards model to produce a nomogram to predict survival from end of treatment. The nomogram was validated externally using data from a trial of MVAC versus docetaxel plus cisplatin (n=148). Results: The median survival from end of treatment was 10.65 months [95% CI 9.20 – 13.24]; 69% of patients had died. Baseline (white blood count, ECOG performance status, number of visceral metastatic sites) and post-treatment (treatment response, duration of treatment, reason for treatment discontinuation) variables were evaluated. The Cox proportional hazard model is shown in the Table. The duration of treatment and reason for treatment discontinuation were not significantly associated with survival. The four significant variables were included in a nomogram. The nomogram achieved a bootstrap-corrected concordance index of 0.68. Upon external validation, the nomogram achieved a concordance index of 0.67. Conclusions: A model derived from pre- and post-treatment variables was constructed to predict survival from the end of first-line chemotherapy in pts with metastatic UC. This model may be useful for pt counseling and for stratification of trials exploring “maintenance” treatment. [Table: see text]