tbuckley/cabot-search huggingface dataset:
Preliminary safety of bevacizumab with first-line Folfox, Capox, Folfiri and capecitabine for mCRC—First B.E.A.Trial
Authors: S. R. Berry, D. Cunningham, M. Michael, M. Dibartolomeo, F. Rivera, A. Kretzschmar, M. Mazier, B. Lutiger, E. Vancutsem
Journal: Journal of Clinical Oncology (2006)

3534 Background: In a phase III pivotal trial in patients (pts) with metastatic colorectal cancer (mCRC), bevacizumab (BEV) increased overall survival by 30% when added to first-line IFL chemotherapy (CT). Safety data from controlled BEV trials have been described, and indicate that certain serious adverse events (SAE), primarily gastrointestinal (GI) perforations and arterial thromboembolic events (TE) occurred more often in pts who received CT with BEV than those who received CT alone. First BEAT was opened to evaluate safety events of BEV in a broader pt population using a variety of CT regimens. Methods: First BEAT started in June 2004 and aims to enrol up to 2000 mCRC pts in 41 countries. Eligible pts starting with first-line CT (physician’s choice) are treated until progression with BEV (5mg/kg q2w [5FU based CT] or 7.5mg/kg q3w [capecitabine based CT]). SAEs include deaths, new and prolonged hospitalizations, life-threatening as well as medically significant events and are reported within 24 hours. There BEV-relatedness is assessed by investigators. Results: By Dec 20, 2005, 1915 pts had been enrolled in 40 countries. 1603/1915 pts (male 58%; median age 59 years [29% were &gt; 65 years]; PS 0–1 99%) had baseline data available for analyses. Median follow-up was 6.7 months (mean 7.3); 1509 pts had been followed-up for &gt;60 days. The most common first-line CT regimens used with BEV were FOLFOX (28%), CAPOX (17%), FOLFIRI (25%) and capecitabine (8%). Among the 1603 pts that had started treatment with BEV, 638 SAEs were reported in 394 pts (25%). 60-day mortality was 2.4%. The most common SAE were diarrhoea 2.7% and pyrexia 2.2% and were usually not attributed as related to BEV. Related SAEs were reported in 132 (8%) pts. venous TE 1.7%, pulmonary embolism 1.1%, bleeding 1.0%, GI perforation 0.9%, arterial TE 0.8%, hypertension 0.5% wound healing complications 0.3% were usually classified as related SAEs. Conclusions: In this ongoing, large community-based study, the safety profile of BEV in first line mCRC pts receiving a variety of CT regimens, namely FOLFOX, CAPOX, FOLFIRI and capecitabine, appears consistent with that observed in large phase III randomised studies. Updated safety data, including grade 3/4 CTC toxicities, will be presented. [Table: see text]
A novel androgen receptor (AR) suppressor complex (ARS)—An essential factor in androgen-independent progression of prostate cancer (PC)
Authors: A. C. Ferrari, L. Wang, E. M. Johnson, J. Melamed, X. Liu, Y. Kinoshita, M. T. Buckley, L. F. Liebes, R. Kurek, L. Ossowski, J. S. Babb
Journal: Journal of Clinical Oncology (2007)

5145 Background: Increased AR level, characteristic of advanced PC, has been linked to AI growth while its down-regulation to restored androgen-dependence (AD). However, the mechanisms of AR overexpression remain in dispute. The objectives were to study the proteins comprising a novel ARS that binds to 5’-UTR of AR gene, which is partially lost in AI LNCaP cells; the status of ARS proteins in AD and AI human specimens and therapeutic modulation of ARS proteins. Methods: Parental AD LNCaP cells and its AI- derivative expressing 4 fold more AR-mRNA and protein than parental AD LNCaP were used to isolate, in vitro/in vivo characterize and therapeutically modulate ARS proteins and cell growth. NYU Tissue Bank provided human samples. Assays: column chromatography, SDS-PAGE, mass spectrometry, EMSA, Southwersten-Western, ChIP, cDNA array, real time PCR, si-RNA, immunohistochemistry. Results: Pur alpha (Pura) and hnRNP-K are part of ARS complex that binds in vitro and in vivo to a defined DNA sequence in 5’UTR of AR gene. AI cells with high AR had 3 times less Pura: its forced expression lowered AR levels. Pura knockdown in AD cells yielded higher AR levels and AI growth. Hormone-naive human PC specimens had significantly increased AR (0.0317) and lower Pura-RNA (0.0317) than hormone resistant PCs. In-vivo binding of Pura (ChIP) to 5’UTR was also reduced (p=0.0028). Histone deactetylase inibitors (HDACI) increased binding of Pura to 5’UTR, decreased AR levels and inhibited AI-growth of LNCaP cells. Conclusions: We show that AR over-expression and AI-growth of a hormone resistant PC cell line are affected by a loss of a repressor complex that binds to 5’-UTR of AR gene. Pura is a crucial part of this complex. We have convincing evidence obtained in hormone naive and resistant human samples to indicate that similar mechanism might be responsible for human PC progression. We determined HDACI can restore Pura levels and androgen-dependence. No significant financial relationships to disclose.
Characterization in healthy human subjects of a method for procuring high quality material for histopathological assessment of cellular proliferation: Buccal punch biopsy
Authors: R. Camidge, M. Pemberton, J. Growcott, P. Laud, J. Foster, K. Randall, A. Hughes
Journal: Journal of Clinical Oncology (2004)

9707 Background: Easily accessible human tissue with a high rate of cell proliferation would be of great utility in the study of antiproliferative agents. The buccal mucosal tissue offers an easily accessible region from which highly proliferating cells can be obtained. In order to investigate the utility of acquiring buccal tissue, we conducted a small feasibility study in healthy male subjects. Objectives were to establish a tolerable procedure, and to determine levels of cell proliferation in the biopsy samples. Methods: Ten subjects underwent the biopsy procedure. Following administration of a local anesthetic (2% lidocaine with adrenaline, AstraZeneca), single punch biopsies (3 mm Stiefel Biopsy Punch, Stiefel Laboratories Ltd, Bucks UK) were taken from the buccal mucosa of each subject and fixed immediately in 10% formal saline for embedding in paraffin. All biopsies were taken within the same 2-hour time window of the 24-hour clock. Results: Two subjects felt momentarily faint after the procedure - no other adverse events were reported. At 24 hours post-procedure tolerability was assessed with a structured questionnaire. All 10 subjects stated that they would undergo the procedure again. Immunohistochemical analysis assessed and quantitated levels of proliferation (expressed as the number of positively stained cells per millimeter of basement membrane) using Ki67 (MIB-1) within the buccal mucosa tissue as 37.2 (range 2.5–108.2) with a CV% of 161.4%. Conclusions: Punch biopsies of the buccal mucosa performed under local anesthesia were well-tolerated and provided good quality tissue for histopathological assessment. The proliferation figures obtained and the tolerability profile of this procedure, suggest that buccal tissue can be used to determine the stimulatory or inhibitory effects of proliferation by novel agents, in small numbers of subjects, during early clinical testing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Genetic Kidney Cancer Syndromes
Authors: Thai H. Ho, Eric Jonasch
Journal: Journal of the National Comprehensive Cancer Network (2014)

Hereditary forms of renal cell carcinoma (RCC) have yielded clues regarding the molecular pathogenesis of sporadic RCC. The discovery of germline mutations in chromatin-modulating enzymes also defined a new hereditary RCC syndrome. Although histologically distinct RCC subtypes exist, emerging themes shared between hereditary and sporadic RCC include dysregulation of the von Hippel-Lindau tumor suppressor protein/hypoxia inducible factor axis, defective ciliogenesis, and aberrant tumor metabolism. This article describes the most common hereditary RCC syndromes and associated extrarenal manifestations. Recent evidence supports developing screening guidelines for early-onset RCC to identify persons with germline mutations in the absence of secondary clinical manifestations.
A randomized phase II study of BMS-247550 (ixabepilone) given daily x 5 days every 3 weeks or weekly in patients with metastatic or recurrent squamous cell cancer of the head and neck
Authors: B. Burtness, M. A. Goldwasser, R. Axelrod, A. Argiris, A. A. Forastiere
Journal: Journal of Clinical Oncology (2006)

5532 Background: Ixabepilone is a novel tubulin-polymerizing agent, with potential activity in SCCHN. Methods: Patients (pts) were eligible who had incurable, measurable SCCHN. ≤ 2 prior regimens for metastatic/recurrent disease were permitted, including taxanes. ECOG PS 0 or 1, ANC ≥ 1500/ml and adequate renal/hepatic function were required. Pts were randomized to ixabepilone 6 mg/m 2 /d 60 minute (min) infusion x 5 days (d) q 21 d [Arm A], or 20 mg/m 2 60 min infusion d1, 8, and 15 q 28 d [Arm B], with diphenhydramine premedication. Tumor assessment was q 6 weeks. Each arm accrued taxane-naive (Tax-N) and -exposed (Tax-E) patients as separate strata, in a 2-stage design. The primary endpoint was response.16 pts entered each group in the first stage. If 1 response was observed in any group, it continued to 32 pts. Results: 85 eligible pts entered. Male 69, ECOG PS (1) 58, metastatic disease 66. 15 Tax-E and 17 Tax-N eligible pts entered stage 1 of Arm A. There were no responses with this dose and schedule. 35 eligible Tax-N pts were accrued to Arm B and 5 had partial responses (14.3%, 90% CI 5.9%,28.2%), 11 stable and 9 progressive disease. 10 in this group were inevaluable (5 died before restaging, 2 were never treated).18 eligible Tax-E pts entered Arm B and none responded. On Arm A, 2/16 Tax-N pts developed grade (gd) 3/4 anemia (13%), and 4/16 (25%) developed gd 3 fatigue. Other gd 3/4 toxicities occurred in &lt; 8% of pts on Arm A. On Arm B, 9/33 (27%) Tax-N pts experienced gd 3/4 leukopenia, 3/33 (9%) gd 3/4 anemia 7 gd 3/4 fatigue (21%), 4 gd 3 nausea (12%), 9 (27%) gd 3 sensory and 2 (6%) gd 3 motor neuropathy. 2/21 Tax-E pts on Arm B experienced gd 4 neutropenia (10%), 6 gd 3 fatigue (29%), 3 gd 3 motor (14%) and 2 gd 3 sensory neuropathy (10%). Median follow up for eligible pts is 31.5 months (mo). 75 have died. Median survival for Arm A Tax-N is 5.62 mo (CI 4.0, 10.0); for Arm A Tax-E is 6.5 mo (CI 2.7, 8.8); for Arm B Tax-N is 7.8 mo (CI 3.3, 8.9) and for Arm B Tax-E is 6.5 mo (CI 2.0, 11.3). Conclusions: Ixabepilone 20 mg/m 2 d1,8,15 q 28 d is active and tolerable in taxane-naive pts with metastatic/recurrent SCCHN. A high incidence of motor and sensory gd 3 neuropathy results at this dose and schedule in patients with previous taxane exposure. [Table: see text]
Matched pair analysis comparing intravenous busulfan and oral busulfan as part of conditioning regimen in autologous stem cell transplantation in high risk neuroblastoma
Authors: A. Prete, R. Rondelli, F. Fagioli, R. Luksch, W. Morello, A. Pession
Journal: Journal of Clinical Oncology (2008)

18003 Background: This case control multicenter study was designed to compare iv Busulfan (Bu) versus oral Bu as part of conditioning regimen in autologous stem cell transplantation (ASCT) in terms of toxicity, 100 days TRM, engraftment kinetics, relapse rate (RR), survival (SUR) and event free survival (EFS), in the treatment of high risk neuroblastoma (HRNB). Methods: Between 2004 and 2007, 12 paediatric patients (Group 1) with HRNB underwent ASCT and received iv Bu every 6 h for a total of 16 doses, + Melphalan (L-PAM). Iv Bu doses were based on accrual patients weight: <9 kg 0.95 mg/kg/dose; 9–16 kg, 1,2 mg/kg/dose; 16–23 kg, 1.1 mg/kg/dose; 24–34 kg, 0,95 mg/kg/; >34 kg, 0,8 mg/kg/dose. 24 paediatric patients (Group 2), underwent ASCT between 1993 and 2007 conditioned with oral Bu, 1 mg/kg/dose every 6 h for a total of 16 doses, + L-PAM ± other were available for selection as appropriate control for matched pairs analysis. Matching criteria were sex, centre, age, disease status, stem cell source, conditioning regimen, days of PMN and PLT engraftment, number of CD34+ infused and grade of toxicity according to Bearman scale. Results: Between the two groups of patients PMN (p = 0.490) and PLT (p = 0.230) engraftment were comparable. 100 days TRMp was 0.00 in Group 1 and 0.04 in Group 2 where 1 patient died for transplant related complications. Two year SURp, EFSp and RRp in Group 1 were 0.77, 0.64 and 0.23 respectively. Two year SURp, EFSp and RRp in Group 2 were 0.69, 0.51 and 0.35 respectively, without significant statistical differences in front of Group 1. After a median follow up of 21 months (range, 3–36), 9/12 patients in Group 1 are alive and well. Conclusions: i.v. Bu in children grafted because affected by HRNB, administered on accrual pt weight, is safe and feasible and in comparison with oral Bu seems less toxic. On the observation of a better outcome in terms of SUR, EFS and RR it is possible to suppose a more efficiency in disease control. No significant financial relationships to disclose.
A Novel 4-anilino-3-quinolinecarbonitrile Dual Src and Abl Kinase Inhibitor (SKI-606) Has In Vitro Activity on CML Ph+Blast Cells Resistant to Imatinib.
Authors: Tiziana Grafone, Manuela Mancini, Emanuela Ottaviani, Matteo Renzulli, Frank Boschelli, Laura Ferraretti, Maria Alessandra Santucci, Marilina Amabile, Simona Soverini, Carolina Terragna, Angela Poerio, Gianantonio Rosti, Cristian Taccioli, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2004)
Cost analysis of febrile neutropenia (FN) management in three tumour types in Germany
Authors: A. Ihbe-Heffinger, B. J. Paessens, C. von Schilling, B. Ehlken, M. Shlaen, K. Berger, A. Görtz, R. Bernard, C. Peschel, V. R. Jacobs
Journal: Journal of Clinical Oncology (2008)

20651 Background: FN is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy (CT). To date there are few data on the costs of FN management in Germany. Methods: Prospective, multicentre, observational, longitudinal study with lymphoma, non small cell lung cancer (NSCLC) and primary breast cancer (PBC) patients (pts). Pts were enrolled consecutively at the start of 1st or 2nd line (immuno-)CT in 4 German hospitals (01/05–12/06). FN was defined as fever >38ºC and ANC <1 × 109/L. If nadir ANC was unavailable, febrile leukopenia (FL) was assessed (fever >38ºC and LC <2 × 109/L). Clinical and resource use data were collected from medical charts. FN associated costs are presented from the provider perspective. Results: Medical charts from 325 pts (47% lymphoma; 37% NSCLC; 16% PBC; 46% women; 38% age ≥65 yrs) were reviewed. FN/FL occurred in 22% of lymphoma, 8% of NSCLC, 27% of PBC and 18% of all pts. In total, 68 FN/FL episodes were identified in 58 pts (see table). Fifty-five FN/FL episodes were associated with ≥1 hospital stay (lymphoma n=34, NSCLC n=10, PBC n=11). Mean±SD cost per FN/FL episode requiring hospital treatment amounted to €3950±4961 (95% CI: 2569, 5331) and varied between €4808±5839 for lymphoma (95% CI: 2666, 6949), €3627±4120 for NSCLC (95% CI: 680, 6574) and €1827±795 for PBC (95% CI: 1293, 2361). Basic hospital costs represented 55% of total costs in lymphoma, 71% in NSCLC and 83% in PBC. Drug treatment made up 22% of total costs in lymphoma, 11% in NSCLC and 9% in PBC pts. Diagnostics generated 8–11% of total direct costs. Conclusions: FN/FL costs vary by tumour type and are highest for pts with lymphoma. Main cost drivers are hospitalisation and drugs. FN/FL pts (%) All (n=58) Lymphoma (n=35) NSCLC (n=9) PBC (n=14) Regimen 54% CHOP-like 80% platinum-based 100% anthracycline-based Female 33 (57) 16 (46) 3 (33) 14 (100) Age ≥ 65 22 (38) 16 (46) 3 (33) 3 (21) ECOG ≥ 2 6 (10) 4 (11) 2 (22) 0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen, Eli Lilly
Decision-making preferences of advanced cancer Hispanic patients from the United States and Latin America.
Authors: Henrique Afonseca Parsons, Sriram Yennurajalingam, Eva Rosina Duarte, Alejandra Palma, Sofia Bunge, J. Lynn Palmer, Marvin Omar Delgado-Guay, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

9063 Background: To determine whether preferences in frequency of passive decision making differ between Hispanic patients from Latin America (HLA) and Hispanic-American (HA) patients. Methods: We conducted a survey of advanced cancer Hispanic patients referred to outpatient palliative care clinics in the U.S, Chile, Argentina, and Guatemala. Information on demographic variables, PS,andMarin Acculturation Assessment Tool (only U.S. patients) was collected. Decision-making preference was evaluated by the decision-making assessment tool. Results: A total of 387 patients with advanced cancer were surveyed: 91 (24%) in the US, 100 (26%) in Chile, 94 (25%) in Guatemala, and 99 (26%) in Argentina. Median age was 59 years, and 61% were female. HLA preferred passive decision-making strategies significantly more frequently with regard to involvement of the family (24% versus 10%, p=0.009) or the physician (35% versus 26%, p&lt;0.001), even after controlling for age and education (OR 3.8, p&lt;0.001 for physician and 2.4, p=0.03 for family) (Table 1). 76/91 HA (83.5%), and 242/293 HLA (82%) preferred family involvement in decision-making (p=NS). No differences were found in decision-making preferences between low- and highly acculturated U.S. Hispanics. Conclusions: HA prefer more active decision-making as compared to HLA. Among HA, acculturation did not seem to play a role in decision-making preference determination. Our findings in this study confirm the importance of family participation in decision making in both HA and HLA. However, HA patients were much less likely to want family members or physicians to make decisions on their behalf. [Table: see text] [Table: see text]
Abstract 12992: Regional Variation in Ischemic Stroke Rates and Oral Anticoagulant Use Among the Non-Valvular Atrial Fibrillation Medicare Population
Authors: Kate Fitch, Kosuke Iwasaki, Kimberly Siu, David R Walker, Bruce Pyenson
Journal: Circulation (2012)

Introduction: The prevalence and economic burden of non-valvular atrial fibrillation (NVAF) among Medicare beneficiaries are high. Examining regional variation in healthcare resource utilization an...
Relationship of peripheral neuropathy grades with increase of skin perfusion by compression therapy for breast cancer patients.
Authors: Tsuyoshi Ohno, Takashi Mine, Hiroki Yoshioka, Mikiko Kosaka, Sadayuki Matsuda, Maiko de Kerckhove, Charles de Kerckhove, Shigetoshi Matsuo, Takashi Azuma, Yuichi Sanada, Takehiro Mishima, Satoshi Inoue, Takashi Hamada
Journal: Journal of Clinical Oncology (2014)

182 Background: Chemotherapy-induced peripheral neuropathy (CIPN) has become a substantial problem because of specific cytotoxic agents such as nab-paclitaxel, oxaliplatin, and eribulin. In addressing CIPN-related side effects caused by nab-PTX, we previously reported better CTCAE v4.0 grades and superior nab-PTX dose maintenance in breast cancer treatment adopting our 3S approach. Our 3S approach combines compression therapy (stockings and sleeves applied 24 hours from the beginning of nab-PTX administration) with medication therapy (selected prophylactic medications goshajinkigan, lafutidine, and mecobalamin applied over the course of treatment). In revisiting how stocking use restored skin perfusion levels decreased by nab-PTX chemotherapy, we examined whether the skin perfusion increases differ by CIPN grade. Methods: Using a laser Doppler blood flow meter with integrated probe (NL-101 Nahri Nexis Japan), we measured the skin perfusion of the lower limbs before and after stocking use across four groups: three groups of 3S prophylactics-treated nab-PTX patients divided by CIPN grade (Grade 0 [G0, n=12], Grade 1 [G1, n=20], Grades 2 and 3 combined [G2+3, n=12]), and one control group of healthy volunteers (GH, n=50). Results: In the control group (GH), the mean increase in skin perfusion level (mL/min/100g) after wearing stockings was 0.90 (SD= 3.36). For the 3S prophylactic treatment patients, the mean increase was 4.25 (4.98) in the G0 group, 2.11 (4.93) in the G1 group, and 2.69 (2.53) in the G2+3 group. ANOVA analysis indicated a significant difference in skin perfusion increase among the groups (p=0.0493). Analysis between the groups indicated significance in the G0 group increase over the control group increase (p=0.0255). Conclusions: CIPN was previously shown to decrease skin perfusion; in the current study skin perfusion responsiveness to stockings differed significantly between chemotherapy patients and healthy volunteers. Restorative skin perfusion increase is potentially related with alleviating CIPN grade, for which further evaluation is needed.
Outcomes of early palliative care referrals for patients with advanced lung cancer.
Authors: Sriram Yennu, Frank V. Fossella, Janet L. Williams, Elyssa A Berg, Tchalla Abalo Mewenenessi, David Hui, Kimberson Cochien Tanco, Gary B. Chisholm, Marieberta Vidal, Hilda Cantu, Maria Guerra-Sanchez, Ashley M Young, Suresh K. Reddy, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

9625 Background: Despite previous studies showing benefits of early referral to palliative care in improving quality cancer care, late referral and under-utilization are major concerns. The aim of this study was to determine the impact of early palliative medicine specialist referral (EPC) on quality cancer care outcomes in advanced lung cancer pts at a comprehensive cancer center. Methods: In this prospective non-randomized controlled study, pts with advanced non-small cell lung cancer with oncologist estimated survival of ≤ 6 months were referred to EPC, N=51. A control group of similar characteristics were recruited from pts with regular follow-up at the thoracic oncology clinic [standard oncology care,UC], N=52. Descriptive statistics and Wilcoxon rank sum tests were used to describe change in FACT-lung, Edmonton Symptom Assessment Scale(ESAS)-symptom distress scores and Hospital Anxiety and Depression Scale(HADS) at follow-up visit. Results: The median age was 61yrs; 52% were female. There was no difference in age, gender, race (p>0.1) at baseline between the two groups, but the EPC pts had a higher symptom burden (EPC 30.5 vs. UC 11.0 p=.001). At follow-up EPC pts had significant improvement in symptoms scores. EPC pts also were more likely to have improved QOL and EOL discussions (Table). Conclusions: EPC was associated with improved symptom distress scores and improved health utilization outcomes, although baseline symptom distress scores were worse in EPC at time of referral. Change in the symptom scores at follow-up and quality-care outcomes in UC and EPC. UC EPC p Median change IQR Median change IQR ESAS symptom distress 5.0 (-2.0,16) -2.5 (-9.7, 6.7) .02 HADS depression 1.0 (0,5.0) -1.0 (-2.0, 3.0) .04 FACIT lung cancer subscale -3.0 (-5.0,1.0) 3.0 (-2.0,5.0) .002 FACT_L TOI -9.0 (-16.0,-1.3) -5.0 (-6.75,10.7) .006 HADS depression (caregiver) .5 (-1.0, 2.2) -1.0 (-4.0,1.0) .025 Quality Metrics ICU sdmissions 4/51 3/52 .68 Median ICU LOS 11 5.0 .21 ICU deaths 1/51 0/52 .38 Any chemotherapy within 14 days of death 3/51 (6%) 1/51 (1%) .3 Hospice referrals 5/51 (10%) 14/52 (27%) .02 Completion of advance directives 2/51 (4%) 9/52 (17%) .03 Discussion of advance care planning 2/51(4%) 34/51 (67%) .001
Correspondence Re: E. Corey et al., Zoledronic Acid Exhibits Inhibitory Effects on Osteoblastic and Osteolytic Metastases of Prostate Cancer. Clin. Cancer Res., 9: 295ndash;306, 2003.
Authors: Daniele Santini, Bruno Vincenzi, Giuseppe Tonini, Susanna Scarpa, Alfonso Baldi
Journal: Clinical Cancer Research (2003)

We read with particular interest the experimental study by Corey et al. [(1)][1] in the “Experimental Therapeutics, Preclinical Pharmacology” section of the January 2003 issue of Clinical Cancer Research . The authors clearly show that zoledronic acid, a new-generation and potent bisphosphonate