bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of antiangiogenic (metronomic) chemotherapy for recurrent malignant gliomas
Authors: Kesari S. , Schiff D. , Doherty L. , Gigas D. , Batchelor T. , Muzikansky A. , O’Neill A. , Drappatz J. , Kieran M. , Wen P. Y. 
Published: March 2020

1569 Background: There is preclinical evidence that continuous low-dose chemotherapy may inhibit tumor endothelial proliferation and prevent tumor growth (Browder et al Cancer Res 2000;60:1878). Methods: We conducted a phase II study of continuous low-dose etoposide (VP-16), alternating with cyclophosphamide (CP), in combination with thalidomide (T) and celecoxib (C) in adult patients with recurrent malignant gliomas. There was no limit on the number of prior therapies. Patients received VP-16 [35 mg/m2 (maximum 100 mg) daily for 21 days] alternating with CP [2 mg/kg (maximum 100 mg/day) for 21 days]. Thalidomide was started at 200 mg daily and increased by 100 mg weekly to a maximum of 1200 mg/day, as tolerated. Celecoxib was started at 200 mg twice daily and increased to 400 mg twice daily. MRIs were performed every 6 weeks. Patients were treated until tumor progression or development of unacceptable toxicity. Serum was collected for measurement of angiogenic peptides. Results: 48 patients were enrolled (15 female, 33 male). 28 had glioblastomas (GBM); 20 had anaplastic gliomas (AG). Median age was 53 years (range 33–74); median KPS was 70 (range 60–100). Patients had average of 2.1 prior chemotherapies; 33% had 3 or more prior chemotherapies. Toxicities included neutropenia (8 G3, 8 G4), leukopenia (13 G3, 8 G4), lymphopenia (26 G3), anemia (1 G3), thrombocytopenia (1 G3); nausea (1 G3), vomiting (3 G3), constipation (5 G3; 2 G4), colitis (2 G4), rash (1 G3), dizziness (1 G3); hypoxia (1 G3), and infection (2 G3). 2 patients had DVT and 6 had pulmonary emboli. There were no treatment related deaths. Fatigue was common but usually mild. 12% of patients had PR, 59% had SD, 29% progressed at their first scan. For GBM patients, median progression-free survival (PFS) was 11 weeks, 6 month-PFS was 9% and median survival was 21 weeks. For AG patients, median PFS was 14 weeks; 6 month-PFS was 26% and median survival was 41.5 weeks. Correlation of angiogenic peptide levels and response will be reported. Conclusions: Although there were some responders this regimen did not significantly improve survival in this heavily pretreated group of patients. However, further studies combining metronomic chemotherapy with more potent angiogenesis inhibitors such as lenalidomide or VEGFR inhibitors may be warranted. [Table: see text]
Regression of pre-established intracranial tumor growth by ON 01910.Na, a selective anticancer agent currently in phase I trials
Authors: Gondi C. S. , Kandhukuri N. , Yanamandra N. , Reddy M. , Reddy E. , Rao J. S. 
Published: March 2020

1576 Background: Despite considerable progress in the treatment modalities used for brain tumors (surgery, radiation therapy and chemotherapy), local recurrence continues to be an important reason for treatment failure. Since multiple regulatory pathways are defective in these tumor cells, novel approaches must tackle more than one mechanism involved in the process of neoplasia. One approach is to effectively combine anti-tumor agents with anti-angiogenic assault. Onconova has developed agents that fit this profile. ON 01910.Na, an injectable product now undergoing Phase I studies at multiple centers, is a potent inhibitor of mitotic progression. It arrests cancer cells in mitosis by depleting cells of CDC25c and efficiently induces apoptosis in the irreversibly arrested cells. Methods: Here, we have evaluated the invasiveness, angiogenesis, and tumorigenicity of glioblastoma cells in both in vitro and in vivo models after treatment with ON 01910. Results: SNB19 cells treated with ON 01910 were significantly inhibited in migration, invasion, and angiogenesis in in vitro models compared to the control group. After treatment with ON 01910, SNB19 cells showed decreased levels of MMPs, uPA, pAKT and PI3 kinase levels compared to controls. Significantly increased levels of PARP, caspase 3 and caspase 9 were also shown. In addition, there was complete regression of pre-established intracranial tumor growth and angiogenesis in in vivo models. The effect was more significant in relation to invasion, angiogenesis and tumor growth when compared to other drugs such as BCNU and Gleevec. Toxicology studies, where ON 01910 was administered systemically or directly into the brain, demonstrate the safey and tolerability of this agent in animals and ongoing Phase I studies indicate that the agent is well-tolerated at dose levels generating pharmacologically relevant concentration of the drug in circulation. Conclusions: These studies validate the potential usefulness of this compound as a novel therapeutic agent for human glioblastoma. [Table: see text]
Frequency of treatment changes observed in chronic myeloid leukemia (CML) patients using imatinib mesylate (IM)
Authors: Devercelli G. , Schulman K. , Song X. , Cheng S. , Davis C. C. 
Published: March 2020

16003 Background: Although the response rates in CML associated with IM treatment is well-documented, little research exists on actual practice patterns with IM. The objective of this study is to document treatment changes in a large CML patient population using IM. Methods: Patients ≥ 18 years of age diagnosed with CML (ICD9 = 205.1) between 2000 and 2004 and treated with IM were selected from the Medstat MarketScan Commercial, Medicaid and Medicare Research Databases. Disease phase was defined using a CML specific disease staging algorithm and was assigned at the time of imatinib initiation. A treatment change is defined as evidence of any of the following: any dose increase ≥50 mg, CML treatment added to IM, or IM discontinuation. Summary statistics reported are medians and interquartile ranges (IQR). Results: Four hundred adult IM-treated CML patients (mean age, 56 years; 50% male) were included. 81% and 18% were in chronic phase (CP) and accelerated phase (AP), respectively; with 1% in remission. IM 400 mg was most frequently used regardless of CML phase or year of treatment. The daily starting dose was 400 mg in 305 (78%) patients, 600–799 mg in 34 (9%) patients, ≥ 800 mg in 17 (4%), and the remaining 39 (9%) started at doses < 400 mg. Median follow-up of treatment duration was 9 (IQR: 4.6, 18.9) months. 158 (40%) patients on IM had at least one treatment change, with rates higher in AP patients than in CP (52% vs. 37%). Dose increases were reported in 108 (27%) patients, 3 (<1%) had additional CML treatment, and 64 (16%) discontinued IM altogether. Conclusions: 40% of patients treated with IM had at least one treatment change. The frequency of treatment change increased with longer duration of IM treatment. [Table: see text] [Table: see text]
Dose increases in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate (IM): Estimated using administrative claims data in a US managed care population
Authors: Davis C. C. , Hines P. , Devercelli G. , Ray S. , Cheng S. , Cortes J. E. 
Published: March 2020

16014 Background: Dose increase is often the first step when resistance is encountered in CML patients treated with IM. The primary objective of this study is to determine the proportion of CML patients who experienced a dose increase from their starting dose within one year after initiation of IM therapy. Methods: Patients ≥18 years of age diagnosed with CML (ICD-9-CM code = 205.1) between 2001 and 2003 and treated with IM were identified in the Pharmetrics Integrated Claims Database which covers a US managed care population. Eligible patients had at least two claims for IM and were continuously enrolled for at least six months following their first IM prescription. Follow-up was one year after their first IM prescription. Results: A total of 113 CML patients using IM were identified. Eighty-four percent of these patients started IM at 400 mg/day; eight percent started at doses ≥ 600 mg/day; remaining started at doses < 400 mg/day The mean daily dose of IM used by the study group was 419 mg (SD = 91). Nineteen percent of users required at least one dose increase from their starting dose within one year. The first dose increase was most frequently 200 mg/day (mean daily dose = 574 mg (SD = 199). The median maximum daily dose reached by patients experiencing dose increases was 600 mg/day (25th– 75th percentile: 500, 750 mg). The median ending dose in these patients was 600 mg/day (25th–75th percentile: 400, 600 mg). Median time to first dose increase was 5.8 (25th–75th percentile: 2.0, 7.4 months). Median time to maximum dose from initial IM dose was 6.5 (25th–75th percentile: 2.7, 7.4 months). Conclusions: Nearly 20% of all IM-treated CML patients required a dose increase of approximately 200 mg/day within one year. Of those dose increases, 50% occurred within the first 6 months. No significant financial relationships to disclose.
End-of-life care resource utilization: A single provider perspective
Authors: Stewart J. A. , Runde D. , Rovick K. , Cleary J. , Grossman J. 
Published: March 2020

16022 Background: Most cancer physicians are aware that significant resources are spent in the last year of life but they are provided little feedback on cost or yield of care. Awareness of resource allocation for patients near the end of life may influence physician conversation with patients and families, treatment recommendations, and hospice referral. Methods: UWHealth cancer registry data were used to identify 90 patients who had died in a recent three year period and were cared for at least in part by the medical oncologist being evaluated. Health services utilization within UWHealth (hospital and hospital based clinic sites) was assessed for the last 6 months of life in 66 patients where a clear date of death could be identified. Data included in- and out-patient, pharmacy, laboratory, radiation and imaging services. Hospice charges are not included. Results: In the last 6 months of life, radiology, radiation therapy and pharmacy charges made up 52% of the total. Use of CT, MRI and palliative radiation increased near the end of life. In the last two months of life, 47% of the entire pharmacy charges were spent. In-patient services were greatly increased in the last month of life. Overall charges and more expensive services were highest in the last month of life. Conclusions: Care near the end of life is expensive. This review targeting patients affiliated with one medical oncologist at a large academic health center showed that radiology, radiotherapy, and pharmacy charges involved more than half the total accrued in the last 6 months of life. Feedback such as this if routinely provided to individual oncologists and disease oriented teams may generate strategies for improving end of life care. Even if expensive, some services may be helpful and necessary, others may not. Discussion regarding accountability for resource allocation within the multidisciplinary setting of cancer care may aid in developing improved end of life approaches for patients. No significant financial relationships to disclose.
Improving quality of care: Challenges to implementing quality indicators
Authors: Owen J. B. , Wilson J. F. 
Published: March 2020

16030 Background: To assess the overall quality of cancer care, efforts seek consensus quality indicators that crosscut health services. Although pilot programs have collected and analyzed relevant clinical data, they have been unable to collect radiation oncology (RO) data detailed enough to assess the quality of services or to inform key decision makers. Quality Research in Radiation Oncology (QRRO) conducted retrospective surveys of national practice since 1973 with major positive impact on the quality of practice through recursive processes. Methods: From Donabedian’s model of quality assessment, QRRO analyzes crucial quality components by conducting Facilities, Process, and Outcomes Surveys. Survey design allows calculation of national averages for patients treated with RO and comparisons by key factors. Evolving data collection methods allow assessment of modern technologies. Methods start with definition and measurement of evidence-based quality indicators but allow greater detail and specification than most other quality measurement efforts. Results: QRRO showed that radiation dose affected outcomes for prostate cancer patients. Higher radiation doses were associated with improved local tumor control rates and treatment techniques affected toxicity rates. These results, presented widely in numerous venues, stimulated dose escalation clinical trials. Trials conducted in the USA all used QRRO results as critical data, providing the major impetus to test new directions in dose escalation and new methods to target delivery more precisely. National practice shifted to higher doses and use of conformal techniques. The dataset is unique in providing cross-sectional information on practice patterns with a wide variety of treatment approaches from many institutions and sufficient details of treatment delivery to allow examination of questions about quality and effects of techniques. Conclusions: Mounting societal demands for improvement in the quality of care, ever increasing complexity of radiation therapy, and escalating use of multi-modality treatment make continuing to measure, report, and improve quality of care in RO crucial to patients and the profession. Methods must keep pace with new technologies and techniques in radiation therapy. [Supported by NCI grant CA 65435]. No significant financial relationships to disclose.
Atypical variant of hypereosinophilic syndrome responsive to imatinib mesylate: A case report
Authors: Kuruvilla J. N. 
Published: March 2020

16530 Background: Idiopathic hypereosinophilic syndrome (HES) was first described by Chusid et al in 1975. The diagnosis of HES rests on three features: A persistent eosinophil count of greater than >1500 cells/μL for more than 6 months, no other etiologies for eosinophilia, and symptoms of organ involvement. The requirement of end organ damage differentiates HES from benign eosinophilia, in which there is no organ damage, in spite of years of eosinophilia. Methods: We present a case of a 28-year-old African American male, admitted for shortness of breath and leg swelling. Past medical history was significant only for asthma. Results: Laboratory investigation demonstrated an average white blood cell count of 15,900 U/L and eosinophilia of 29.6% over a 6-month period. Stool studies for ova and parasite, Rheumatoid factor, antinuclear antibody, pANCA, cANCA and complements were within normal limits. Thyroid stimulating hormone, liver function studies, and erythrocyte sedimentation rate were within normal limits. IgE level was 158 (mildly high). Peripheral smear showed only mature eosinophils. A bone marrow biopsy showed a hypercellular marrow consistent with an atypical variant of HES. Cytogenetic studies did not reveal any clonal abnormalities. Trans-esophageal echocardiogram showed severe mitral regurgitation. During the hospital course the patient had a mitral valve replacement with a St. Jude’s mechanical valve and mitral valve pathology showed post inflammatory changes and ventricular myocardial biopsy staining for eosinophilic major basic protein confirmed eosinophilic changes. The patient remained refractory to aggressive steroid therapy, and was started on imatinib mesylate, which lead to a complete remission. Conclusions: HES is a very rare and often fatal condition. A 1989 French study showed a 5-year survival of 80%, and a 15-year survival of 42%. HES has three known variants: The atypical myeloproliferative variant of HES is often refractory to glucocorticosteroid therapy, but responds to treatment with the tyrosine kinase inhibitor, imatinib mesylate. No significant financial relationships to disclose.
A phase II study of the safety and efficacy of the MDR inhibitor VX-710 combined with doxorubicin and vincristine in small cell lung cancer
Authors: Gandhi L. , Harding M. , Neubauer M. , Langer C. J. , Crawford J. , Moore M. , Rooney J. , Ross H. , Einhorn L. H. , Johnson B. E. , Lynch T. J. 
Published: March 2020

17001 Background: Tumors with multidrug resistance (MDR) frequently show upregulation of efflux proteins MDR protein (MRP-1) and P-glycoprotein (Pgp). MDR represents a major obstacle to successful chemotherapy treatment and can be reversed in Pgp or MRP1-expressing cells by the MDR inhibitor VX-710. A phase II study was designed to evaluate the safety/tolerability and efficacy of VX-710 combined with doxorubicin (D) and vincristine (V) in patients (pts) with relapsed SCLC. Methods: Eligible pts had progressive, measurable disease and a PS <2 after response to 1st-line chemotherapy. Stage I safety evaluation was done with planned expansion to a second stage if 9 responses were confirmed in the first 35 pts. Pts were treated with VX-710 (120 mg/m2/h) for 72 hours with D (45 mg/m2) and V (1.4 mg/m2) given 4 hours after the start of VX-710. Pts were treated q 21 days until progression or intolerable adverse events (AEs). Severe neutropenia was noted in the first 15 pts, so the protocol was amended to include prophylactic G-CSF or ciprofloxacin. Interim analysis was performed after 36 pts were treated. Results: 36 pts were enrolled from 12/98 to 12/00. Neutropenia was the major toxicity, occurring in 25/36 (69%) pts. This was more severe (30% vs. 20% grade 4) and occurred earlier (58% vs. 38% in cycle 1) among the 15 pts enrolled prior to an amendment requiring neutropenia prophylaxis vs. those enrolled afterward. Other common treatment-related AE’s: asthenia (53%), nausea (50%), constipation (44%), alopecia (42%), dyspnea (42%), anemia (42%). 67% were grade 1 or 2 in severity. Four pts died on study or within 30 days of termination: 2 from infections likely related to therapy and 2 from disease progression. Among 32 evaluable pts, 7 (22%) had partial responses; 6 of these sustained responses through 6 cycles (with one response lasting 3 years). Three additional pts had unconfirmed responses. Median survival was 6 months (95% CI 4–7 months). Conclusions: The addition of VX-710 to D and V therapy did not improve anti-tumor activity or survival. Hematologic toxicity was severe, causing 2 pt deaths from neutopenic fever. Although there were some durable responses, response criteria were not met to proceed with stage 2. Further development with VX-710 has since stopped. [Table: see text]
Phase II trial of oxaliplatin and gemcitabine with bevacizumab in first-line advanced non-small cell lung cancer (NSCLC)
Authors: Davila E. , Lilenbaum R. , Raez L. , Seigel L. , Tseng J. , Graham P. 
Published: March 2020

17009 Background: Oxaliplatin-Gemcitabine (GemOx) is an active and well tolerated. Bevacizumab (BV) prolongs survival when combined with carboplatin-paclitaxel. This phase II trial evaluates the efficacy of GemOx + BV as 1st line therapy for advanced NSCLC patients. Methods: Pts with stage IIIB (effusion) and IV non-squamous NSCLC, ECOG PS 0 or 1, no CNS metastasis, and no other contraindications to BV, are eligible. Prior therapy for earlier-stage disease allowed if completed at least 12 months before enrollment. Treatment consists of Gem 1000 mg/m2 on d1 and 8, Ox 130 mg/m2 on d1, and BV 15 mg/kg on d1, repeated every 3 wks for a total 4 cycles. Pts who respond or have stable disease receive BV maintenance until progression. Main endpoints are response rate (RR), grade (Gr) 3–4 toxicities, time to progression (TTP), and overall survival (OS). Results: As of 12/05, 26 out of 50 projected pts have been enrolled from 4 institutions. M/F 17/9; median age 65y (45,81); IIIB/IV 3/23; PS 0/1 8/18. Median F/U time is 3.7 months. 24 pts are evaluable for toxicity: 1Gr3 ANC; 1Gr3 and 4 PLT; no FN.3 Gr3 diarrhea and 2 Gr3 N/V; 1Gr3 and 4 hypophosphatemia; 1 pt had ischemic bowel after the 1st cycle, recovered fully and was removed from study; 1 pt died of liver failure in the 1st cycle. No bleeding complications have occurred. 22 pts are evaluable for RR (ITT): 7 PR (31%); 8 SD (36%). TTP and OS data not yet available. Conclusions: This is the first report of GemOx in combination with BV in advanced NSCLC. This regimen has minimal hematologic toxicity but selected non-hematologic toxicities are noted. Activity appears promising and merits further investigation. Accrual is ongoing. [Table: see text]
Phase II study of docetaxel and carboplatin in elderly patients with advanced non-small cell lung cancer
Authors: Yoshimura N. , Kudoh S. , Kimura T. , Mitsuoka S. , Hirata K. 
Published: March 2020

17013 Background: Single-agent chemotherapy has been considered as standard treatment for elderly patients with non-small cell lung cancer (NSCLC). However recent subset analyses suggest that platinum-based combination chemotherapy may be safely administered to the elderly with good performance status (PS). We evaluated the efficacy and safety of carboplatin and docetaxel in a phase II study of elderly patients aged 70 years or older. Methods: Chemotherapy-naive patients aged ≥70 years with advanced NSCLC (IIIB-IV), ECOG performance status (PS) of 0 or 1, a measurable lesion, and adequate organ functions were enrolled. Patients received carboplatin (AUC 5) and docetaxel (60 mg/m2) administered on day 1 every 3 weeks. The primary endpoint was response rate (RR). This study, with a planned sample size of 25, had 80% power to support the hypothesis that the true RR was >30%, and 5% significance to deny the hypothesis that the true RR was <10%. Results: Between October 2003 and September 2005, 26 elderly patients with NSCLC were enrolled in the study and all patients were treated. Demographics: M/F 17/9; PS 0/1 2/24; median age 75 (range 70–84). Median number of treatment cycles was 4. Responses in the 26 evaluable patients included 1CR; 12PR; 7SD; for an objective RR of 50% (95% CI 31–69%) and a disease control rate of 77%. Median survival period and 1-year survival rate have not yet been reached. Grade 3/4 hematologic toxicities included leukopenia (82%), neutropenia (86%), thrombocytopenia (5%) and anemia (5%). Non-hematologic toxicities were mild with no grade 4 toxicities; grade 3 nausea (9%), anorexia (23%), diarrhea (14%), fatigue (9%), allergic reaction (9%) and infection (18%) were observed. Conclusions: The combination of carboplatin and docetaxel was safe and promising for the treatment of chemotherapy-naive elderly patients with advanced NSCLC. This regimen warrants further evaluation in a phase III trial. No significant financial relationships to disclose.