tbuckley/cabot-search huggingface dataset:
Update on AVOREN trial in metastatic renal cell carcinoma (mRCC): Efficacy and safety in subgroups of patients (pts) and pharmacokinetic (PK) analysis
Authors: B. J. Escudier, A. Ravaud, S. Négrier, C. Szczylik, J. Bellmunt Molins, S. Bracarda, P. Pisa, J. Gaudreault, E. Bajetta
Journal: Journal of Clinical Oncology (2008)

5025 Background: Results from the phase III AVOREN trial have shown that first-line treatment with bevacizumab (BEV; Avastin®) + interferon-α2a (IFN) significantly improves progression-free survival (PFS) in pts with mRCC compared with IFN + placebo (median: 10.2 vs 5.4 mths, HR=0.63; p=0.0001). Pts with predominantly (>50%) clear cell RCC were eligible for inclusion. Methods: A retrospective analysis was conducted to determine the efficacy of BEV + IFN in subgroups of pts with reference to histology, renal function and baseline VEGF levels. BEV and IFN concentrations were determined. All pts had undergone nephrectomy, allowing tumour histology to be more accurately determined than with biopsy, and had a KPS score ≥70%. Creatinine clearance (CLcr) was calculated based on creatinine values at baseline (normal CLcr, ≥75mL/min in males and ≥65mL/min in females). Results: 85 (13%) pts in the AVOREN trial had a mixture of clear cell (>50%) and other histology mRCC. The remainder had clear cell only. In these subgroups, BEV + IFN almost doubled the median duration of PFS compared with IFN alone (mixed: 5.7 vs 2.9 mths; clear cell only: 10.2 vs 5.5 mths). The PFS benefit due to BEV was similar in pts with baseline VEGF levels below or above the median and pts with high/normal and low baseline CLcr. Cox regression analysis indicated no association between baseline VEGF levels and BEV efficacy (p=0.1507) or CLcr and BEV efficacy (p=0.5108). Of those pts who received BEV and developed hypertension or proteinuria, 63% and 64% were progression-free at 12 mths, respectively, compared with 43% in the overall BEV population. BEV PK in mRCC were similar to pts with other tumour types and no relationship between CLcr and BEV AUC was observed. BEV did not affect the PK of IFN. Conclusions: BEV + IFN significantly improves PFS in pts with mRCC, irrespective of tumour histology. The efficacy of BEV appears to be independent of baseline VEGF, renal function or the development of hypertension or proteinuria. AVOREN subgroup HR (95% CI) Histology Mixed (n = 85) 0.53 (0.33–0.85) Clear cell only (n = 564) 0.64 (0.53–0.77) VEGF Below median (n = 191) 0.44 (0.32–0.64) Above median (n = 191) 0.66 (0.49–0.93) CLcr High/normal (n = 262) 0.60 (0.46–0.79) Low (n = 376) 0.65 (0.51–0.82) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Bayer, Inate Pharma, Pfizer, Roche, Schering-Plough, Wyeth Roche Antigenics, Bayer, Genentech, Novartis, Pfizer, Roche, Wyeth GlaxoSmithKline, Roche Bayer, Novartis, Pfizer
The prognostic significance of sentinel lymph node detection in malignant melanoma.
Authors: L. Gales, A. Rodica Maricela, X. Bacinschi, I. Isacu, A. Tarlea
Journal: Journal of Clinical Oncology (2011)

e19000 Background: Malignant melanoma represent one of the most studied malignancies, due to its highly increasing incidence but also due to the lack of efficacy of the known therapies in advanced stages. The most important prognostic factors remain the thickness of invasion and the lymph node status. In our study we intend to follow the role of sentinel node dissection in the prediction of metastatic spread. We try to find a correlation between histological evaluation of sentinel lymph node and time to recurrence. Methods: The patients were included after resection of malignant melanoma and referral to the Institute of Oncology. 30 patients were included between Jan 2007 and Dec 2007. After surgery the patients were staged using imagistic methods (CT or MRI) and sentinel lymph node detection and biopsy. The patients receive treatment according to their stage (Interferon for locally advanced stages, chemotherapy for metastatic stages and no treatment for early stages). Patients with distant metastases were excluded. All the patients were followed for recurrence using the same imagistic method as at baseline, every three month. Results: There were stages: T1a – 3 pts, T1b – 4 pts, T2a – 6 pts, T2b – 7 pts, T3a – 2 pts, T2b – 3 pts, T4a – 0 pts, T4b – 5 pts. The localization of the primary tumor was: head and neck – 1 pt, trunk – 10 pts, upper limb – 6 pts, lower limb – 13 pts. Sentinel lymph node was positive in 2 patients (inguinal lymph nodes), one with T1b and one with T2b stage. The patients with ulcerated tumors receive adjuvant interferon low dose. The patients with positive lymph node receive adjuvant high dose interferon. None of the patients with positive lymph node developed distant metastases at two year follow up interval. One of the patients with pN0sn (initial T4b stage) developed distant metastases at 6 months after sentinel node biopsy. Conclusions: Sentinel lymph node biopsy represents the best method for lymph node staging. The presence or absence of sentinel lymph node invasion represents one of the most important prognostic factors for malignant melanoma. The lymph node stadialization have a major impact in adjuvant treatment selection.
Net Clinical Benefits of Ticagrelor Compared With Clopidogrel in Asian Acute Coronary Syndrome Patients : A Plato Sub-Study
Authors: Hyun-Jae Kang, Robert M. Clare, Runlin Gao, Anders Himmelmann, Claes Held, Lars Wallentin, Stefan James, Richard C. Becker
Journal: Circulation (2013)

Net Clinical Benefits of Ticagrelor Compared With Clopidogrel in Asian Acute Coronary Syndrome Patients : A Plato Sub-Study
Malignant melanoma in the first three decades of life: A report from the U.S. Surveillance, Epidemiology and End Results (SEER) Program
Authors: A. Pappo, L. Ries, C. Herzog, A. Bleyer
Journal: Journal of Clinical Oncology (2004)

7557 Background: Melanoma during the first three decades of life is rare, and small numbers of patients have precluded meaningful comparisons in children, adolescents and young adults. Methods: Using the SEER database, we investigated the incidence, clinical presentation, and outcome of melanoma in the first three decades of life. Results: The estimated incidence of melanoma in the year 2000 per million individuals increased with age and was projected to be projected to be 4.0 for 10–14yr olds (y/o), 15.5 for 15–19y/o, 44.4 for 20–24y/o, and 73.8 for 25–29y/o. Projecting prior trends to the year 2000, this equates to 114 new cases/yr among those < 15yr and 2586 cases/yr among those 15–29 yr. Melanoma accounted for < 3 % of all cancers in 0–14 yr olds, for 7.1% of all cancers in the 15–19yr age group, and for over 12% of all cancers in the 20–30-yr age group. From 1988–1999, the distribution of melanoma according to stage was as follows: < 20yr of age: in situ (n=99[number of cases];23%[% of total group]), localized (n=315;73%), nodal extension (n=17;4%). In the 20–29-yr group: in situ (n=525;18%), localized (n=2125;76%), nodal-regional disease (n=153;5%), and distant disease (n=20;1%). Among pts < 20 yr with localized disease, 212 tumors (70%) measured < 1 mm and 15 (5%) were > 4 mm. For pts 20–30yr, 1600 (75%) measured < 1 mm and 57 (3%) measured > 4 mm. Survival by stage for both groups (< 20 yr and 20–30yr) was nearly identical: in situ tumors (100% vs 99%), localized disease (97% vs 96%), nodal disease (60% vs 62%). Conclusions: About 8% of melanomas occur in patients < 30 yr of age, a patient population that has been underrepresented in clinical trials (Bleyer A et al: www.asco.org/asco/ascoMainConstructor/1,47468, 12| 002199,00.asp). The presenting features and outcome of melanoma in the first three decades of life appears similar to that of older patients and the prognosis appears to be stage dependent. These findings strongly argue in favor of developing cooperative group trials for melanoma that allow enrollment of younger age groups. No significant financial relationships to disclose.
Effect of granulocyte-macrophage colony stimulating factor (GM-CSF) administered with a multipeptide vaccine on circulating CD8<sup>+</sup> and CD4<sup>+</sup> T-cell responses: Outcome of a multicenter randomized trial
Authors: C. L. Slingluff, G. R. Petroni, W. C. Olson, M. E. Smolkin, M. I. Ross, N. B. Haas, W. W. Grosh, M. E. Boisvert, J. M. Kirkwood, K. A. Chianese-Bullock
Journal: Journal of Clinical Oncology (2009)

3008 Background: GM-CSF administered locally with vaccines can augment T-cell responses in animal models. Human experience with GM-CSF has mostly occurred in uncontrolled or nonrandomized trials. Thus, a multicenter prospective randomized phase II trial was performed to determine whether local administration of GM-CSF augments immunogenicity of a multipeptide vaccine administered in an emulsion with an incomplete Freund's adjuvant (IFA). A second component of the trial was designed to assess whether the vaccine administered in two sites is more immunogenic than in a single site. Methods: 121 eligible and evaluable patients with resected stage IIB-IV melanoma were administered a sequence of multipeptide vaccines, each consisting of 12 MHC Class I-restricted melanoma peptides (12MP) to stimulate CD8 + T cells, plus an HLA-DR restricted tetanus helper peptide to stimulate CD4 + T cells. Peptides were emulsified with IFA, with or without GM-CSF. T cell responses were assessed by IFN-gamma ELIspot assay and tetramer analysis, weekly x 8. Clinical outcome was evaluated for all patients. Results: Vaccination was well-tolerated, and each peptide was immunogenic. Overall CD8 + T-cell response rates to the 12MP (days 1–50), for patients vaccinated with or without GM-CSF were 43% and 75%, respectively (p &lt; 0.001), and response magnitude was almost twice as high in patients without GM-CSF. Class I MHC tetramer analyses corroborated the functional data. There was also a greater CD4 + T-cell response to the tetanus helper peptide without GM-CSF than with it (95% and 77%, respectively, p = 0.005). There was no significant difference in immune response rates by the number of vaccine sites. For the entire patient group, 3-year overall and disease-free survival estimates [95% CI] were 76% [67, 83%] and 52% [43, 61%], respectively. There have been too few events to assess differences in clinical outcome by study arm. Conclusions: High immune response rates were achieved with this multipeptide vaccine, but CD8 + and CD4 + T-cell responses appear to be partially suppressed with addition of GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans. [Table: see text]
Alpha 1 Antitrypsin, C Reactive Protein, and Hemolysis Markers: Association With Cytokines Profile In Sickle Cell Disease Patients In Steady-State and Crisis-State
Authors: Magda Carvalho, Wendell Vilas Boas, Bruno Antônio Veloso Cerqueira, Joao Oliveira Reis, Theo Araujo, Larissa Rocha, Nivea Luz, Valma Lopes, Valeria Borges, Marilda Souza Goncalves
Journal: Blood (2013)
The impact of perioperative red blood cell transfusion on long-term survival after hepatectomy for colorectal liver metastases.
Authors: Julie I. Hallet, Melanie Tsang, Eva Cheng, Iryna B. Kulyk, Sherif Hanna, Calvin Law, Natalie G. Coburn, Paul Jack Karanicolas
Journal: Journal of Clinical Oncology (2015)

725 Background: Perioperative red blood cell transfusions (RBCT) are associated with postoperative morbidity and may increase cancer recurrence through immunologic mechanisms following resection of colorectal liver metastases (CRLM). We sought to explore the relationship between RBCTs and long-term survival following resection of CRLM in the contemporary surgical era. Methods: We conducted a retrospective review of a prospective database including all patients undergoing partial hepatectomy for CRLM from 2003-2012. Data regarding date of death was abstracted from a validated, population-based cancer registry. Primary outcome was overall survival (OS), compared based on RBCT (defined as time of surgery to 30 days following surgery) and on number of RBC units received using Kaplan-Meier curves. Cox regression analysis was performed to examine the association between RBCT and OS, while adjusting for prognostic factors including Fong score and period of treatment (2003-2007 vs. 2008-2012). Results: We included 483 patients operated for CRLM, of which 27.5% received RBCT. 90-day post-operative mortality was 4.8% and median follow-up was 33 (IQR: 20.1-54.8) months. Median survival in patients who received RBCT was 44.5 months compared with 93.5 months in patients who did not(p&lt;0.0001). The difference persisted in subgroup analysis excluding patients who died within 90 days of surgery (62.3 vs. 93.5 months, p=0.023). After adjustment for Fong score and period of treatment, RBCT was independently associated with decreased OS (HR 2.15; 95% CI: 1.52-3.04). Conclusions: Perioperative RBCT is independently associated with decreased OS following hepatectomy for CRLM. Interventions to minimize and rationalize the use of RBCT for hepatectomy are warranted in order to mitigate this detrimental effect on long-term outcomes.
A phase I pharmacokinetic (PK) trial of XAA296A (Discodermolide) administered every 3 wks to adult patients with advanced solid malignancies
Authors: A. Mita, A. C. Lockhart, T.-L. Chen, K. Bochinski, J. Curtright, W. Cooper, L. Hammond, M. Rothenberg, E. Rowinsky, S. Sharma
Journal: Journal of Clinical Oncology (2004)

2025 Background: XAA296A is a natural product isolated from the marine sponge Discoderma dissoluta. It stabilizes microtubules more potently than paclitaxel and has activity against paclitaxel-refractory xenografts. Methods: In this phase I trial, XAA296A was administered IV as a fixed infusion rate of 0.77mg/ml/min once every 3 weeks. Results: 26 pts (17 M, 9 F) have been treated at the following dose levels (mg/m2): 0.6 (3 pts); 1.2 (3 pts); 2.4 (4 pts); 4.8 (4 pts); 9.6 (4 pts); 14.4 (6 pts) and 19.2 (2 pts). The median age = 59.5 (19–79). All patients had KPS ≥70%. 9/ 26 received prior taxane therapy. No drug related DLTs have occurred to date. G1 pain and burning at site of injection was noticed at initial dose levels but resolved with central administration of XAA296A. One patient had G4 anemia during third cycle. Number of patients with G2/3 adverse events with suspected relationship to XAA296A (all cycles): Anemia (5,1), Nausea (6, 0), Vomiting (3, 1), Fatigue (5, 1), Diarrhea (4, 0), Mucositis (2, 0), Stomatitis (1,0), Pruritus (1,0), ↑Alk phos (1,0), ↑ Creatinine (1,0), Myalgias (1,0). No neuropathy or neutropenia has been observed. One patient with appendix carcinoma had stable disease for 4 cycles. PK of XAA296A was evaluated in 24 pts after the 1st and 2nd dose using noncompartmental approach. Concentrations were determined by an LC/MS/MS method. XAA296A concentrations showed Cmax at the end of infusion, thereafter declining rapidly in a multiphasic manner. By 24 h post-dose, blood concentrations had decreased to <10% of Cmax, but then showed nonlinear PK, evidenced by a convexity of the terminal phase on a semi-log scale. This was observed in the majority of concentration-time profiles, suggesting prolonged recycling of drug between tissue and the systemic circulation. AUClast, Cmax, and MRTlast ranged from 103–15211 ng*h/ml, 29–482 ng/ml, and 32–162 h, respectively. Conclusions: XAA296A is a novel microtubule stabilizer which has minimal toxicities in this phase I trial. In addition, it demonstrates nonlinear PK characterized by a second broad peak at the terminal phase. Dose accrual is continuing to define the phase II dose. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp.
Phase II evaluation of bi-weekly docetaxel combined with doxorubicin in patients with locally advanced breast cancer
Authors: K. Crew, A. Tiersten, L. Vahdat, T. Frank, H. Hibshoosh, S. Smith, L. Brafman, E. Schwartzreich, D. Hershman
Journal: Journal of Clinical Oncology (2004)

879 Background: For patients with locally advanced breast cancer neoadjuvant chemotherapy is considered the standard of care, but the optimal regimen has yet to be defined. Methods: This phase II study evaluates the efficacy of neoadjuvant Docetaxel 50mg/m2 and Doxorubicin 35mg/m2 q2 weeks for 6 cycles in locally advanced breast cancer patients (pts). Eligible subjects were stage IIB-IIIB, had measurable disease, ECOG PS≤2. Results: Between Dec 01-Dec 03, 12 pts were evaluable; median age: 59 (32–72), stage IIB/IIIA/IIIB: 1/4/7, median tumor size: 4.5cm (2.3–7.8), ER+/PR+: 7/7, Her-2/neu+: 8, ECOG PS 0/1/2: 9/2/1. All 12 pts completed 6 cycles. Out of 72 total cycles, 3 treatment delays occurred due to low WBC, mucositis and a line infection, respectively. The main toxicity was neutropenia, grade 4 (3 pts) and 3 (2), but no episodes of neutropenic fever. 8 pts received prophylactic Ciprofloxicin, 5 G-CSF. Treatment of 12 pts resulted in 5 PR, 6 SD and 1 PD. There were no complete pathologic responses; median tumor size after chemotherapy: 3.1cm (0–7), median number of positive lymph nodes: 3 (1–14). All pts were inoperable at diagnosis and were made operable following chemotherapy, including 3 lumpectomies. Median OS and PFS were not reached. After a median follow-up of 19 months (4–24), 2 deaths occurred, 1 pt is alive with disease, and 9 are NED. Conclusions: This regimen is well-tolerated and effective with a response rate including minor responses of 92%. Given the good clinical response and minimal side-effects, further evaluation at higher doses with G-CSF support is warranted. No significant financial relationships to disclose.
Serotonin receptor antagonists are no better than prochlorperazine for control of delayed nausea (DN) caused by doxorubicin: A URCC CCOP study of 701 pPatients
Authors: J. T. Hickok, G. R. Morrow, J. A. Roscoe, J. L. Wade, S. R. Dakhil, J. P. Kuebler, P. Bushunow
Journal: Journal of Clinical Oncology (2005)

8006 Background: Despite the widespread use of first generation serotonin receptor antagonists, DN occurs in 75% or more patients after treatment with doxorubicin. Methods: 701 patients were enrolled on a randomized clinical trial comparing three regimens to control DN. All were chemotherapy-naïve, receiving their first course of chemotherapy containing doxorubicin and were given a short-acting 5-HT3 receptor antagonist antiemetic with dexamethasone on the day of treatment (Day 1). Participants were randomly assigned to one of three regimens for Days 2 and 3. Arm 1: prochlorperazine (Compazine) 10 mg p.o. three times daily; Arm 2: Any 5-HT3 antiemetic using standard dosing regimens; Arm 3: prochlorperazine 10 mg p.o. p.r.n. Results: Patients taking prochlorperazine regularly were less likely to have DN (72%) than those taking prochlorperazine p.r.n. (82%, p = 0.013), or those taking a serotonin receptor antagonist (79%) p = 0.07. There were no significant differences in mean or peak DN severity between the three regimens. DN severity at its worst on Days 2–4 averaged 3.6 for the prochlorperazine regularly and the 5-HT3 treatment arms and was 3.9 for prochlorperazine p.r.n (Scale 1–7, with 1 = no nausea). For all patients together, mean as well as peak nausea severity were significantly greater during the delayed period than on Day 1 (p <0.001, both). Significantly more patients on the 5-HT3 arm took rescue medications than patients on either of the two prochlorperazine arms (5-HT3 = 34%, prochlorperazinep.r.n. = 19%, prochlorperazine regular = 21%, P < 0.001). Conclusions: None of these three regimens is adequate to control delayed nausea. Short-acting 5-HT3 antiemetics, used in the delayed period, were no more effective against either mean or peak delayed nausea severity than was prochlorperazine. Better prevention and treatment of delayed chemotherapy-associated nausea is needed. Supported by NCI PHS grant U10 CA37420 No significant financial relationships to disclose.
The influence of HAART on HIV-associated primary cerebral lymphoma: Declining incidence and improving survival
Authors: M. Bower, D. Mazhar, T. Newsom Davis, T. Powles, S. Mandalia, B. Gazzard, J. Stebbing
Journal: Journal of Clinical Oncology (2006)

17512 Background: The risk of primary central nervous system lymphoma (PCL) is increased in individuals infected with the human immunodeficiency virus type-1 (HIV-1). As highly active anti-retroviral therapy (HAART) has reduced morbidity and mortality secondary to HIV, we investigated the effect of HAART on the presentation and outcome of HIV infected individuals with PCL. Methods: From a single centre cohort of 9,621 HIV infected individuals, patients with PCL were identified. We compared pre-HAART and HAART era clinico-pathologic variables and investigated whether exposure to anti-retrovirals with differing CNS penetrations, protected from the development of this AIDS-defining illness. Results: In 61 patients diagnosed with PCL and a median survival of 1.3 months, we observed a decreased incidence of PCL in the HAART era compared to the pre HAART era (χ 2 p = 0.0001), and a significantly improved overall survival (Log rank p = 0.032). In the HAART era there were fewer patients with prior AIDS defining illnesses (χ 2 p = 0.015) and patients were significantly more likely to have the diagnosis confirmed histologically or by CSF PCR examination (χ 2 p &lt; 0.0001). Exposure to specific anti-retrovirals did not protect from the development of PCL, regardless of cerebro-spinal fluid (CSF) penetration. Conclusions: Although the prognosis remains dismal, the HAART era has decreased the incidence and prolonged the survival of individuals with HIV-1 associated PCL. No significant financial relationships to disclose.