bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II study of belinostat (PXD101) in patients with unresectable hepatocellular carcinoma
Authors: Yeo W. , Lim R. , MA B. B. , Hui P. , Chan L. , Mo F. K. , Yu S. C. , Ho S. S. , Koh J. , Chan A. T. , Goh B. 
Published: March 2020

15081 Background: Hepatocellular carcinoma (HCC) is a common cause of cancer morbidity and mortality. It is a highly aggressive tumor with 90% presenting with unresectable disease, resulting in a median survival of 3–6 months. Inhibitors of histone deacetylase (HDAC) have been demonstrated in HCC cell lines and xenografts to induce apoptosis and tumor regression, and have anti-proliferative, anti-metastatic and anti-invasive effects. Belinostat (N-hydroxy-3-[phenylsulphamoylphenyl] acryl amide) is a novel, low molecular weight, HDAC inhibitor. The Cancer Therapeutic Research Group (CTRG) is conducting a phase I/II study of belinostat as the first line therapy for pts with unresectable HCC. The phase I study aims to determine dose limiting toxicity (DLT) and maximum tolerated dose (MTD). Methods: Patient eligibilities include histologically or cytologically confirmed unresectable HCC, ECOG = 2, adequate hematologic, renal and hepatic functions. The dose of belinostat was started at 600 mg/m2/day i.v. on day 1–5 every 3 weeks; with increment of 300 mg/m2/day up to 1200 mg/m2/day. Dose limiting toxicities (DLT) are defined as grade 4 hematological toxicity or grade 3 or 4 nonhematological toxicity during cycle 1 (according to NCI CTC v3), or treatment delay >2 weeks. The MTD is defined as the dose below which ≥ 2 of 3 or ≥ 2 of 6 patients experiencing DLT. After determination of the MTD, 3 additional patients will be treated at this dose to further define toxicity. Results: From June-December 2006, 12 pts were entered; 3 were treated at level I (600 mg/m2/day), 3 at level 2 (900 mg/m2/day), and 6 at level 3 (1200 mg/m2/day). There were no DLTs on level 1, 2 or 3. Therefore, the MTD of belinostat was not reached. Overall toxicities were WBC gr. 0/1/2/3/4: 12/0/0/0/0, ANC gr. 0/1/2/3/4: 12/0/0/0/0; Hb gr. 0/1/2/3/4: 4/7/0/1/0; platelet gr. 0/1/2/3/4: 8/4/0/0/0; lethargy gr. 0/1/2/3: 12/0/0/0/0, phlebitis gr. 0/1/2/3: 10/0/2/0; Cough gr. 0/1/2/3: 9/0/3/0; Nausea gr. 0/1/2/3: 7/3/2/0 and vomiting gr. 0/1/2/3: 9/3/0/0. Conclusions: At the maximum dose of 1200 mg/m2/day (level 3), MTD has not been reached. Belinostat is very well tolerated. Phase II study will be started at dose level 1200 mg/m2/day. Sponsor: The Division of Cancer Treatment and Diagnosis, National Cancer Institute, USA. No significant financial relationships to disclose.
Impact of flaxseed supplementation and dietary fat restriction on prostate cancer proliferation and other biomarkers: Results of a Phase II randomized controlled trial (RCT) using a presurgical model
Authors: George S. L. , Polascik T. J. , Albala D. M. , Walther P. J. , Moul J. , Madden J. F. , Snyder D. C. , Hars V. , Switzer B. R. , Vollmer R. T. , Demark-Wahnefried W. 
Published: March 2020

1510 Background: Diet may play a key role in the etiology of prostate cancer (PC). Dietary fat restriction (DFR) and flaxseed supplementation (FS) may reduce risk, though results are mixed. We undertook an RCT to test the comparative effects of these dietary regimens on the biology of the prostate and other biomarkers. Methods: PC patients (N=161) scheduled ≥ 21 days prior to prostatectomy were block randomized on race (black vs non-black) and biopsy Gleason sum (<7 vs 7+) to these diets: 1) control; 2) FS (30 g/day); 2) DFR (<20% total energy); or 4) FS+DFR. Blood was drawn upon accrual and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin (SHBG), total testosterone (T), insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), c- reactive protein (CRP), and total and low density lipoprotein cholesterol (TC & LDL-C). Proliferation (MIB-1) and apoptosis (TUNEL) was assessed in the malignant and benign prostate. Results: Complete data were collected on 93% of the sample; mean length on protocol was 30 days. Median MIB-1 positive (+) cells/total nuclei ratios were: 1=2.38;2=1.71;3=2.93;4=1.58. Primary analyses suggest a significant protective effect (p=0.016) of FS. Secondary analyses of MIB-1 + nuclei (controlling for total cell counts) show increased proliferation with DFR (p=.017), and a significant interaction with FS and DFR (p<.0001). No differences were observed between groups with regard to PC apoptosis, and histology of benign tissue. No differences were observed between arms for PSA, SHBG, T, IGF1, IGFBP3 or CRP. Significant differences were observed between arms for changes in serum lipids and body weight [ΔTC = +9/-26/-46/-37 mg/dL; ΔLDLC = -14/-17/-29/-21 mg/dL and Δ weight = +0.3/-1.3/-1.7/-1.1 kg (p’s<.05)]; effects were attributed to DFR and not FS. Side effects did not differ between arms Conclusions: Preliminary findings suggest that FS is safe and exerts a protective effect (main effect or via interaction with DFR) on PC. Data also provide further support of DFR for cardiovascular disease, though its role in PC is less clear. Further controlled analyses and additional studies are needed to confirm findings. No significant financial relationships to disclose.
Paclitaxel poliglumex (PPX), cisplatin and concurrent radiation for esophageal and gastric cancer: A phase I study
Authors: Dipetrillo T. , Evans D. , Akerman P. , Miner T. , Millis R. , Jean M. , Henderson D. , Oldham F. , Eisenfeld A. , Safran H. 
Published: March 2020

15130 Background: PPX is a conjugate of paclitaxel to a polyglutamate polymer. Preclinically, PPX demonstrated a radiation enhancement factor (REF) >7.0, versus 1.5–2.0 for paclitaxel. (Milas et al Int J Rad Onc 55:2003, Li et al. Clin Cancer Res 6:2000). The maximally tolerated dose (MTD) of PPX was determined previously to be 70 mg/m2 /week with concurrent radiation. We initiated a phase I study of PPX, cisplatin, and concurrent radiation with patients with esophageal and gastric cancer. Methods: Patients with esophageal or gastric cancer receiving chemoradiation for locoregional control, adjuvant, or neoadjuvant treatment were eligible. All patients received radiation at a dose of 50.4 Gy delivered in 28 fractions (5 fractions per week for 5 1/2 weeks), and cisplatin (25 mg/m2) on days 1, 8, 15, 22, 29, and 36. PPX was given as a 10 minute infusion in escalating dosages prior to each cisplatin dose. Dose limiting toxicities (DLTs) were defined as grade 4 hematologic toxicity, esophagitis, nausea/vomiting, or dehydration, or any other grade 3/4 non-hematologic toxicity. Patients were enrolled in successive cohorts of three. The MTD was defined as the dose level at which no more than 2 of 6 patients have DLTs. Results: Eleven patients have been entered over 2 dose levels of PPX: 50 mg/m2 (six patients, dose level 1), and 60mg/m2 (5 patients, dose level 2). Five patients had esophageal cancer and six had gastric cancer. All histologies were adenocarcinomas. One of six patients treated at dose level had a DLT (esophagitis). Three of five patients had DLTs at dose level 2, including esophagitis, nausea, vomiting, and dehydration. Conclusions: PPX is a novel radiation sensitizer for patients with esophageal and gastric cancer. The MTD for PPX is 50 mg/m2 /week in combination with cisplatin 25mg/ m2 /week for 6 weeks, and 50.4 Gy concurrent radiation for patients with esophagogastric cancer. A phase II study of PPX/cisplatin and radiation will be initiated. No significant financial relationships to disclose.
A phase II study of amplitude-modulated electromagnetic fields in the treatment of advanced hepatocellular carcinoma (HCC)
Authors: Costa F. , de Oliveira A. C. , Meirelles R. , Zanesco T. , Surjan R. , Chammas M. , Barbault A. , Pasche B. 
Published: March 2020

15155 Background: Phase I data show that low levels of electromagnetic fields modulated at specific frequencies administered intrabucally with the THERABIONIC device are a safe and potentially effective treatment for advanced cancer. The device emits a 27.12 MHz radiofrequency signal, amplitude-modulated at tumor-specific frequencies ranging from 0.2 to 23,000 Hz. The device is connected to a spoon- like coupler placed in the patient’s mouth during treatment. Patients with advanced HCC and limited therapeutic options were offered treatment with HCC-specific frequencies. Methods: From October 2005 to October 2006, 38 patients with advanced HCC were recruited in a phase II study. The patients received three daily 40 min treatments until disease progression or death. The median age was 64.0 ± 14.2 years. 32 patients were male and 29 patients had documented progression of disease (POD) by IV contrast imaging prior to study entry. 8 patients had not received prior therapy because of metastases (3), poor medical condition (3), declined chemotherapy (2). Results: As of January 2007, 12 patients are still on therapy, 20 patients died of tumor progression, 2 patients are lost to follow-up and 3 patients withdrew consent. 27 patients are eligible for response. The overall objective response rate as defined by partial response (PR) or stable disease (SD) in patients with prior documented POD was 31.6%: 3 PR and 9 SD. The median survival was 20.7 weeks with a median duration of therapy of 17.5 weeks. 13 patients have received therapy for more than six months. The median duration of response is 12.9 weeks. 12 patients reported pain at study entry: 8 of them (66%) experienced decreased pain during treatment. There were no NCI grade 2/3/4 toxicities. One patient had grade 1 mucositis and grade 1 fatigue. Conclusion: In patients with advanced HCC, THERABIONIC is a safe and effective novel therapeutic option, which has significant anti-tumor effect and provides pain relief in the majority of patients. [Table: see text] No significant financial relationships to disclose.
The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Subset analysis of patients (pts) with brain metastases (BM)
Authors: Henderson C. A. , Bukowski R. M. , Stadler W. M. , Dutcher J. P. , Kindwall-Keller T. , Hotte S. J. , Logie K. , Baltz B. , Wilson K. , Figlin R. A. 
Published: March 2020

15506 Background: Sorafenib (SOR) was demonstrated to be safe and effective in a phase III trial of previously treated RCC pts; however, pts with BM were excluded. BM occur in 5–10% of RCC pts, and generally portend a poor prognosis. Safety and efficacy of SOR in this pt population was therefore explored in a subset analysis of ARCCS, a community-based expanded access program. Methods: Pts received SOR 400 mg bid in this open-label, nonrandomized trial if they were =15 years old with advanced RCC and had ECOG PS of 0–2. Pts with BM were included but required to have some prior local therapy for their brain lesions. Prior treatment did not have to be successful, and pts whose BM had been surgically removed were also eligible for this protocol. BM were excluded as target lesions for RECIST unless they were the only lesions being followed. Major exclusion criteria included treatment with other investigational drugs within 4 wks of enrollment; life expectancy <2 mos; active coronary artery disease, ischemia, or hypertension; and severe renal impairment requiring dialysis. The primary endpoints were safety and efficacy (per investigator assessed RECIST criteria). Results: Of 2,488 ARCCS pts valid for safety, 65 (2.6%) had been previously treated for BM: 72.3% male with median age 59.5 yrs. 99% had =1 prior therapy for non-brain disease including 81.5 % radiotherapy, 78.5% nephrectomy and 47.7% prior systemic therapy. Grade 3 adverse events (AE) occurring >2% in this subset were fatigue and seizure (6.2% each) and hand-foot skin reaction, diarrhea, hemoglobin, mucositis, dehydration, vomiting, hyperglycemia, and thrombosis (3.1% each). In the total ARCCS population vs the BM subset, Grade 3 AEs were 35.2% vs 26.2% and Grade 4 AEs were 6.1% vs 9%. There were no CNS-related bleeding events in pts with BM. Of the 47 pts evaluable for response, partial response was reported in 2 (4%), stable disease in 33 (70%), and progressive disease in 12 (26%). Conclusions: The toxicity and efficacy of SOR in pts with brain mets in ARCCS were comparable to those observed in the whole study population. Of note, SOR was well tolerated in this study with no reports of cerebral hemorrhagic events. [Table: see text]
A phase II trial of gefitinib monotherapy in patients with unresectable adrenocortical carcinoma (ACC)
Authors: Samnotra V. , Vassilopoulou-Sellin R. , Fojo A. T. , Oh W. K. , LaRocca R. V. , Ernstoff M. S. , Memoli V. A. , Cole B. F. , Quinn D. I. , Simmons P. A. , Tretter C. P. 
Published: March 2020

15527 Background: ACC is a rare malignancy with a very poor prognosis. Surgery is the only potential curative option. Gefitinib is an oral EGFR inhibitor that may have activity in solid tumors that express EGFR. ACC over expresses EGFR in a high proportion of cases. Methods: From April 2004 through December 2006, the ACC Working Group conducted a phase II trial of Gefitinib as second line, monotherapy in patients with pathologically confirmed unresectable ACC who had progressed on mitotane or chemotherapy. All prior systemic therapy was discontinued 28 days prior to starting gefitinib. Patients were ineligible if: had received prior therapy with any EGFR inhibitor, pregnant or breast feeding, had other co-existing malignancies (other than basal cell carcinoma or cervical cancer in situ), had an ECOG PS > 2, absolute neutrophil counts < 1,500, or platelets < 20,000. Patients were not allowed concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John’s Wort. Patients took gefitinib 250 mg orally once a day. Each cycle was 21 days with radiological assessment every 6 weeks.Response rate as determined by RECIST criteria was the primary endpoint. Results: 19 patients accrued to the study (18 with measurable disease and 1 without). Pt Characteristics: Female 79% (15/19); Median age 48 (range 26–74); 84% (12 female and 4 male =15/19) of the patients had steroid secreting tumors. Grade 3 toxicity was noted in 2 patients and included, hypertension and lower extremity edema and elevated liver transaminases. No grade 4 toxicities occurred. Of 19 patients evaluable, there were no complete responders, partial responders or patients with stable disease (0% response rate; 95% CI: 0%-18%). Conclusions: Gefitinib demonstrated no activity in patients with unresectable ACC. This study is now closed. This study demonstrated the ability to successfully accrue to a trial of novel agents in rare tumors in a multicenter setting. [Table: see text]
Sunitinib-related macrocytosis in patients with advanced renal cell cancer (RCC)
Authors: Price J. A. , Shaarbaf R. , Wood L. A. 
Published: March 2020

15580 Background: Sunitinib is an oral multi-targeted tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity approved and widely used for the treatment of advanced RCC. Based on a clinical observation that several RCC patients receiving Sunitinib developed macrocytosis, this study was performed to describe and examine macrocytosis in this patient population. Methods: A retrospective review of all patients treated with Sunitinib for RCC from 08/05–11/06 was performed. Data regarding hematologic parameters (e.g. CBC, mean corpuscular volume- MCV), concomitant medications, liver function, and time on therapy (cycle length varied from 4–7 weeks) was recorded. Vitamin B12 and folate levels, iron studies, and thyroid function were recorded if available. A standardized, laboratory-specific MCV was used to define macrocytosis. Results: 43 patients formed the study cohort, receiving a median of 4 cycles (24 weeks) of Sunitinib. Overall 19 (44%) patients developed macrocytosis, at a median of 3 cycles (16 weeks). Of the 31 patients who received > 2 cycles of Sunitinib, 48% developed macrocytosis compared to 33% of the 12 patients receiving =2 cycles. Among all patients with macrocytosis, only 8 (42%) had anemia at the time. Of the 24 patients who did not become macrocytic, 19 (79%) had a continual rise in their MCV during therapy. Other causes of macrocytosis including vitamin B12 and folate deficiency, hypothyroidism, and other medications, did not contribute to the macrocytosis identified in this cohort. On preliminary analysis, it did not appear that macrocytosis was associated with response or toxicity. Conclusions: This is the first study to document the common occurrence of Sunitinib-associated macrocytosis in RCC patients. The risk of macrocytosis increased with duration of treatment. Macrocytosis did not appear to be associated with significant clinical sequelae; however this, as well as the mechanism of macrocytosis, requires further study. No significant financial relationships to disclose.
Induction cetuximab (C) followed by C, paclitaxel (P), carboplatin (CP) and concurrent radiation (RT) for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Birnbaum A. E. , Johnson T. T. , Rathore R. , Khurshid H. , Puthawala M. , Radie Keane K. , Ruhl C. , Wanebo H. , Kennedy T. , Ready N. 
Published: March 2020

16504 Background: C is an IgG1 chimerized, monoclonal antibody that binds specifically to the epidermal growth factor receptor, which is expressed in 90–100% of HNC. We conducted a phase II study to evaluate the toxicity and efficacy of induction C followed by concurrent C with chemoRT for patients (pts) with SCCHN. Methods: Eligible pts had untreated stage III or IV, SCCHN. All pts received induction, single agent, C, 400 mg/m2 week 1, followed by 250 mg/m2 weeks 2, 3, and 4. Potentially operable pts then received C, 250 mg/m2, P 40 mg/m2 and CP AUC=1, weekly x 5 wks, with 45 Gy RT then underwent endoscopic biopsy. If the biopsy was negative, pts received 3 additional weekly doses of C, P, CP and 22–27 Gy boost RT. Inoperable pts received 8 weeks of C, P and CP and 66.6–72 Gy RT. All pts then received maintenance C 250 mg/m2/week x 24 weeks. Results: 29 pts have been enrolled. Male:Female 18:11. Median age = 55 (38–75). Primary sites included oral cavity (10 pts), oropharynx (1), larynx (12), hypopharynx (2), and glottis (4). The tumor stages were III (10 pts), IV (19). Toxicity data are available for 23 pts. 2 of 23 (9%) had grade (G) 4 toxicities (hypokalemia =1, ischemic colitis=1) however there were no treatment related deaths. G 2 toxicities included rash (52%), dysphagia (35%), mucositis (43.5%) and hypomagnesemia (9%). G 3 toxicities included rash (9%), dysphagia (44%), mucositis (26%) and XRT dermatitis (18%). Induction C responses by RECIST criteria were SD (14 pts) 61%, PR (7) 30%, and CR (1) 4%. Conclusion: C can be safely administered with chemoRT (CRT) for pts with HNC. C increases cutaneous toxicity but does not increase in-field CRT side effects. There were no unexpected high-grade adverse events. Preliminary single agent activity of C in untreated SCCHN is promising. No significant financial relationships to disclose.
Phase II trial of satraplatin and paclitaxel in the first-line treatment of advanced non-small cell lung cancer
Authors: Shipley D. , Spigel D. R. , Cavanaugh C. , Moore Y. , Hainsworth J. D. , Jones S. , Burris H. A. , Sade L. , Yardley D. A. , Greco F. 
Published: March 2020

18073 Background: Satraplatin (S) is a novel oral platinum analogue that has shown promising activity in a number of solid tumor settings. Our center previously conducted a phase I trial combining S and paclitaxel (P) in patients (pts) with refractory malignancies, establishing safety for this combination. This single center community-based trial was designed to examine the role of S/P in pts with newly diagnosed advanced non-small cell lung cancer (NSCLC). Methods: The primary endpoint is the objective response rate (ORR). Eligibility criteria: newly diagnosed and unresectable stage IIIB/IV NSCLC, measurable disease, ECOG PS 0–2, and informed consent. Treatment: S 80 mg/m2 PO days 1–5 and P 200mg/m2 IV day 1, every 28 days for a maximum of 6 cycles. Pts were restaged every 8 weeks. Results: 28 pts were enrolled from 2/06 to 12/06 (trial ongoing, n = 40 planned). Data are available on 24 pts for analysis. Baseline characteristics: median age 67 years; male/female, 58%/42%; and ECOG PS 0/1/2, 25%/63%/12%; adenocarcinoma/squamous/large cell/unspecified, 33%/42%/1%/24%. The ORR was 17% (95% CI 5%-37%). 10 pts (42%) had stable disease (SD) and 5 pts (21%) had progressive disease. The disease control rate (ORR + SD) was 59%. 5 pts were not evaluable due to: death (3 pts - 1 possibly due to treatment- related sepsis), and physician/pt preference (1 pt each). With a median follow-up of 8.3 months, the median time to progression is 4 months. Grade (G) 3/4 non-hematologic toxicity occurring in = 5%: infection (29%), nausea, vomiting (17% each), anorexia, hyperglycemia (13% each), and fatigue (8%). G3/4 hematologic toxicity: leukopenia (21%), neutropenia (41%), and thrombocytopenia (29%). Conclusions: In this preliminary analysis, S/P appears to have comparable activity to other platinum-based regimens. In an effort to reduce myelosuppression this trial has been amended to a S dose of 70 mg/m2. Additional accrual and follow-up are needed to better assess the safety and efficacy of this combination regimen. No significant financial relationships to disclose.
Randomized phase II trial of erlotinib (E) versus temozolomide (TMZ) or BCNU in recurrent glioblastoma multiforme (GBM): EORTC 26034
Authors: Van Den Bent M. J. , Brandes A. , Rampling R. , Kouwenhoven M. , Kros J. M. , Carpentier A. F. , Clement P. , Klughammer B. , Gorlia T. , Lacombe D. 
Published: March 2020

2005 Background: In 40–50% of GBM epidermal growth factor receptor (EGFR) is amplified, and often constitutively activated (EGFRvIII mutant). EGFR is therefore a potential therapeutic target. Previous studies suggested activity of EGFR tyrosine-kinase inhibitors in recurrent GBM, particularly in specific molecular subsets. This study explored erlotinib (E) activity in recurrent GBM. Methods: Randomized phase II trial. Eligibility criteria: histologically proven GBM, recurrent >3 months after radiotherapy, Karnofsky performance status (KPS) =70, no prior chemotherapy for recurrent disease, tissue sample for EGFR studies. Patients (pts) received E 150mg/day (300mg/day if on enzyme inducing anti-epileptic drugs [EIAEDs]), or control (TMZ 150–200mg/m2, day 1–5 q4wk or BCNU 60–80mg/m2 i.v., day 1–3 q8wk). If no significant toxicity, E was escalated to 200mg (500mg in patients on EIAEDs). The primary endpoint was 6 months’ PFS in =10/50 pts on E (20%); P0 was set at 15%, and P1 at 30%. Response was assessed with Macdonald’s criteria. EGFR amplification (FISH) and expression of EGFR, EGFRvIII and PTEN (immunohistochemistry [IHC]) were assessed. Results: 110 patients were randomized (54 E, 56 control: 27 TMZ; 29 BCNU). Median age 55 years; median KPS 90. All but 1 patient started treatment; median number of cycles was 2 for E, 4 for TMZ and 1 for BCNU. Grade 3/4 toxicities likely related to E: dermatological (5); hemorrhage (1). Grade 3/4 toxicities for control were mainly hematological (3 TMZ, 13 BCNU). Three pts discontinued E due to toxicity. Six-month PFS was 12% for E, 24% for control. Six and 12-month survival were 61% and 24% for E, and 63% and 26% for control. Two responses were seen on control; the best response on E was SD (n=6). Patients with EGFRvIII mutations (13 in E arm, 8 in control arm) had shorter PFS (p=0.007) and OS (p=0.004) regardless of treatment. Response to E was not correlated with EGFR expression, EGFR amplification or EGFRvIII mutation. Conclusions: This randomized, controlled phase II study did not find sufficient activity for erlotinib in the general population of recurrent GBM. The presence of EGFRvIII mutations was not predictive for response. No significant financial relationships to disclose.