bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Evaluation of Once-Weekly Dosing of Epoetin Alfa in Chemotherapy Patients: Improvements in Hemoglobin and Quality of Life Are Similar to Three-Times-Weekly Dosing
Authors: Gabrilove Janice L. , Cleeland Charles S. , Livingston Robert B. , Sarokhan Brenda , Winer Eric , Einhorn Lawrence H. 
Published: February 2017

PURPOSE: To prospectively evaluate the effectiveness, safety, and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients. PATIENTS AND METHODS: A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomized study conducted in 600 United States community-based practices. Patients received epoetin alfa 40,000 U once weekly, which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks. RESULTS: Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy–Anemia questionnaire. Improvements in quality-of-life parameters correlated significantly (P < .001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy. CONCLUSION: The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy. Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule.
Combined Interferon-Alfa, 13-cis-Retinoic Acid, and Alpha-Tocopherol in Locally Advanced Head and Neck Squamous Cell Carcinoma: Novel Bioadjuvant Phase II Trial
Authors: Shin Dong M. , Khuri Fadlo R. , Murphy Barbara , Garden Adam S. , Clayman Gary , Francisco Marites , Liu Diane , Glisson Bonnie S. , Ginsberg Lawrence , Papadimitrakopoulou Vassiliki , Myers Jeffrey , Morrison William , Gillenwater Ann , Ang K. Kian , Lippman Scott M. , Goepfert Helmuth , Hong Waun Ki 
Published: February 2017

PURPOSE: Retinoids and interferons (IFNs) have single-agent and synergistic combined effects in modulating cell proliferation, differentiation, and apoptosis in vitro and clinical activity in vivo in the head and neck and other sites. Alpha-tocopherol has chemopreventive activity in the head and neck and may decrease 13-cis-retinoic acid (13-cRA) toxicity. We designed the present phase II adjuvant trial to prevent recurrence or second primary tumors (SPTs) using 13-cRA, IFN-α, and α-tocopherol in locally advanced-stage head and neck cancer. PATIENTS AND METHODS: After definitive local treatment with surgery, radiotherapy, or both, patients with locally advanced SCCHN were treated with 13-cRA (50 mg/m2/d, orally, daily), IFN-α (3 × 106 IU/m2, subcutaneous injection, three times a week), and α-tocopherol (1,200 IU/d, orally, daily) for 12 months, with a dose modification. Screening for recurrence or SPTs was performed every 3 months. RESULTS: Tumors of 11 (24%) of the 45 treated patients were stage III, and 34 (76%) were stage IV. Thirty-eight (86%) of 44 patients completed the full 12-month treatment (doses modified as needed). Toxicity generally was consistent with previous IFN and 13-cRA reports and included mild to moderate mucocutaneous and flu-like symptoms; occasional significant fatigue (grade 3 in 7% of patients), mild to moderate hypertriglyceridemia in 30% of patients who continued treatment along with antilipid therapy, and mild hematologic side effects. Six patients did not complete the planned treatment because of intolerable toxicity or social problems. At a median 24-months of follow-up, our clinical end point rates were 9% for local/regional recurrence (four patients), 5% for local/regional recurrence and distant metastases (two patients), and 2% for SPT (one patient), which was acute promyelocytic leukemia (ie, not of the upper aerodigestive tract). Median 1- and 2-year rates of overall survival were 98% and 91%, respectively, and of disease-free survival were 91% and 84%, respectively. CONCLUSION: The novel biologic agent combination of IFN-α, 13-cRA, and α-tocopherol was generally well tolerated and promising as adjuvant therapy for locally advanced squamous cell carcinoma of the head and neck. We are currently conducting a phase III randomized study of this combination (v no treatment) to confirm these phase II study results.
Prognostic Significance of Reverse Transcriptase Polymerase Chain Reaction for Prostate-Specific Antigen in Men With Hormone-Refractory Prostate Cancer
Authors: Kantoff Philip W. , Halabi Susan , Farmer Deborah A. , Hayes Daniel F. , Vogelzang Nicholas A. , Small Eric J. 
Published: February 2017

PURPOSE: To evaluate the prognostic significance of reverse transcriptase polymerase chain reaction (RT-PCR) detection of prostate-specific antigen (PSA) mRNA in the blood of men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Peripheral blood was obtained from 193 men enrolled on Cancer and Leukemia Group B Study 9480, a prospective randomized comparison of three doses of suramin. RNA was isolated from the samples and assayed for the presence of PSA transcripts by RT-PCR. RESULTS: RNA could be isolated in 156 (83%) of samples. PSA transcripts as measured by RT-PCR were detectable in 75 (48%) of the 156 patients. The median survival for those patients in whom no transcripts were detectable was 18 months (95% confidence interval [CI], 14 to 22 months) compared with 13 months (95% CI, 11 to 15 months) (P = .004) for those in whom transcripts were detectable. In a multivariate analysis in which other factors predictive of survival were used, RT-PCR for PSA provided independent prognostic information. CONCLUSION: RT-PCR for PSA predicts survival duration in a population of men with HRPC.
Clinical Impact of Germ Cell Tumor Cells in Apheresis Products of Patients Receiving High-Dose Chemotherapy
Authors: Bokemeyer C. , Gillis A. J.M. , Pompe K. , Mayer F. , Metzner B. , Schleucher N. , Schleicher J. , Pflugrad-Jauch G. , Oosterhuis J. W. , Kanz L. , Looijenga L. H.J. 
Published: February 2017

PURPOSE: High-dose chemotherapy (HD-Ctx) followed by autologous peripheral-blood stem-cell (PBSC) transplantation is currently investigated in patients with poor prognosis or relapsed metastatic germ cell tumor (GCTs). This study analyzed the presence and the clinical importance of contaminating tumor cells in PBSC preparations used to support HD-Ctx in GCT patients. PATIENTS AND METHODS: Seven targets for reverse transcription polymerase chain reaction (RT-PCR)-based detection of GCT cells were able to detect seminomatous and different histologic variants of nonseminomatous tumor cells. PBSC preparations from 57 patients were investigated for the presence of contaminating tumor cells using this set of targets, including beta human chorionic gonadotropin (β-hCG), fibronectin (EDB variant), epidermal growth factor receptor (EGFR), CD44 (v8 to 10 variant), germ cell and placental alkaline phosphatase (AP), human endogenous retrovirus type K (ENV and GAG), and XIST. Samples of PBSC preparations from four healthy donors for allogenic transplantations as well as blood specimens from 10 healthy volunteers served as negative controls. RESULTS: Fifty patients (43 first-line and seven second-line Ctx) were assessable. Combining all RT-PCR results, 29 PBSC preparations (58%) were positive for tumor-specific amplification products (HERV-K 0, fibronectin 4, XIST 14, β-hCG 19, AP 19, CD44 24, EGFR 26). Ten (35%) of 29 patients who underwent transplantation with positive PBSC preparations and seven (33%) of 21 patients with negative PBSC preparations have suffered relapse or progression (not significant [ns]). With a median follow-up of 22 months (2 to 66) post–HD-Ctx projected 3-year survival rates are 68% (RT-PCR+) and 58% (RT-PCR−) (ns). None of the 10 control peripheral-blood samples showed positivity for any of the targets studied. CONCLUSION: GCT cells can be detected in more than 50% of PBSC preparations using a RT-PCR approach with multiple targets. Despite the presence of tumor cells, retransplantation of the PBSC products did not effect long-term outcome. Factors such as responsiveness to chemotherapy and tumor mass seem to overcome the importance of potentially re-infused tumor cells.
Bony Morbidity in Children Treated for Acute Lymphoblastic Leukemia
Authors: Strauss Adam J. , Su Joyce T. , Dalton Virginia M. Kimball , Gelber Richard D. , Sallan Stephen E. , Silverman Lewis B. 
Published: February 2017

PURPOSE: Corticosteroids are widely used in the treatment of acute lymphoblastic leukemia (ALL). To determine the frequency of corticosteroid-associated bony morbidity in children with ALL, we retrospectively evaluated the incidence of fractures and osteonecrosis (ON) on two consecutive pediatric ALL protocols. PATIENTS AND METHODS: One hundred seventy-six consecutive children were treated for ALL between 1987 and 1995 at the Dana-Farber Cancer Institute and Children’s Hospital. Prednisone was used as the corticosteroid during postremission therapy from 1987 to 1991, and dexamethasone was used from 1991 to 1995. Medical records for all patients were reviewed to assess the occurrence of fractures and ON. RESULTS: With a median follow-up of 7.6 years, the 5-year cumulative incidence (CI) ± SE of any bony morbidity for the 176 patients was 30% ± 4%, with a 5-year CI of fractures of 28% ± 3% and of ON of 7% ± 2%. With multivariate analysis, independent predictors of bony morbidity included age 9 to 18 years at diagnosis (P < .01), male sex (P < .01), and treatment with dexamethasone (P = .01). Dexamethasone was associated with a higher risk of fractures (5-year CI, 36% ± 5% v 20% ± 4% with prednisone; P = .04), but not ON (P = .40). The 5-year event-free survival for the 176 patients was 79% ± 3%. CONCLUSION: Children treated for ALL had a high incidence of fractures and ON. Older children, boys, and patients receiving dexamethasone were at increased risk for the development of bony morbidity. Future studies should attempt to minimize corticosteroid-associated bony morbidity without compromising clinical efficacy.
Delay of the Diagnostic Lumbar Puncture and Intrathecal Chemotherapy in Children With Acute Lymphoblastic Leukemia Who Undergo Routine Corticosteroid Testing: Tokyo Children’s Cancer Study Group Study L89-12
Authors: Manabe A. , Tsuchida M. , Hanada R. , Ikuta K. , Toyoda Y. , Okimoto Y. , Ishimoto K. , Okawa H. , Ohara A. , Kaneko T. , Koike K. , Sato T. , Sugita K. , Bessho F. , Hoshi Y. , Maeda M. , Kinoshita A. , Saito T. , Tsunematsu Y. , Nakazawa S. 
Published: February 2017

PURPOSE: To determine the effects of eliminating initial lumbar punctures in 418 consecutively treated children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Patients were enrolled onto a trial conducted in central Japan between 1989 and 1992. Treatment consisted of standard four-drug induction therapy followed by a risk-based intensification phase, reinduction therapy, late intensification, and remission maintenance therapy (total of 104 weeks). The initial lumbar puncture, with an intrathecal injection of chemotherapy, was performed after 1 week of prednisolone sensitivity testing (day 8). End points included response to prednisolone, CNS status at the time of the day 8 lumbar puncture, subsequent adverse events in CNS and bone marrow, and event-free survival (EFS). RESULTS: The remission induction rate was 93.1% with a 6-year EFS rate (± SE) of 68.7% ± 2.4%, which is similar to historical results for patients who received their diagnostic lumbar puncture and first instillation of intrathecal chemotherapy on day 0. Overall, 84.5% of the patients had good responses to prednisolone, whereas 15.5% had poor responses. Clinical outcome was strikingly better for the good responders (6-year EFS, 74.1% ± 2.5% compared with 40.1% ± 6.4% for patients with poor responses), suggesting that omission of intrathecal chemotherapy did not alter the predictive value of drug sensitivity testing. Eighteen patients experienced CNS relapse as their first adverse event (cumulative risk, 5.1%; 95% confidence interval, 2.7% to 7.4%), coincident with reports from groups using conventional strategies of CNS clinical management. Bleeding into the CSF at the time of the day 8 lumbar puncture was apparent in 29 cases (8.1%), but leukemic blasts were identified in only two. CONCLUSION: Delay of the initial lumbar puncture and intrathecal injection of chemotherapy seems to be feasible in children with ALL. Further controlled evaluations are needed to establish the validity of this conclusion.
Phase I Study of Anti–Epidermal Growth Factor Receptor Antibody Cetuximab in Combination With Radiation Therapy in Patients With Advanced Head and Neck Cancer
Authors: Robert Francisco , Ezekiel Mark P. , Spencer Sharon A. , Meredith Ruby F. , Bonner James A. , Khazaeli M. B. , Saleh Mansoor N. , Carey Delicia , LoBuglio Albert F. , Wheeler Richard H. , Cooper Michael R. , Waksal Harlan W. 
Published: February 2017

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of a chimeric anti–epidermal growth factor receptor monoclonal antibody, cetuximab, in combination with radiation therapy (RT) in patients with advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We treated 16 patients in five successive treatment schedules. A standard dose escalation procedure was used; three patients entered onto the study at each dose level of cetuximab received conventional RT (70 Gy, 2 Gy/d), and the final three patients received hyperfractionated RT (76.8 Gy, 1.2 Gy bid). Cetuximab was delivered as a loading dose of 100 to 500 mg/m2, followed by weekly infusions of 100 to 250 mg/m2 for 7 to 8 weeks. Circulating levels of cetuximab during therapy were determined using a biomolecular interaction analysis core instrument. Human antichimeric antibody response was evaluated with a double-antigen radiometric assay. The recommended phase II/III dose was defined as the optimal cetuximab dose level based on the pharmacologic parameters and adverse events. RESULTS: The most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities (grade 1 to 2 in most patients). Skin toxicity outside of the RT field was not strictly dose-dependent; however, grade 2 or higher events were observed in patients treated with higher dose regimens. There was one grade 4 allergic reaction. Most acute adverse effects were associated with RT (xerostomia, mucositis, and local skin toxicity). No antibodies against cetuximab were detected. All patients achieved an objective response (13 complete and two partial remissions). CONCLUSION: Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m2 and a maintenance weekly dose of 250 mg/m2.
Eligibility for Hematopoietic Stem-Cell Transplantation for Primary Systemic Amyloidosis Is a Favorable Prognostic Factor for Survival
Authors: Dispenzieri Angela , Lacy Martha Q. , Kyle Robert A. , Therneau Terry M. , Larson Dirk R. , Rajkumar S. Vincent , Fonseca Rafael , Greipp Philip R. , Witzig Thomas E. , Lust John A. , Gertz Morie A. 
Published: February 2017

PURPOSE: Based on the success of hematopoietic stem-cell transplantation (HSCT) for multiple myeloma, HSCT is being used to treat patients with primary systemic amyloidosis (AL). This article addresses the extent to which eligibility to undergo HSCT is a favorable prognostic feature and explores prognostic factors within the subset of eligible patients. PATIENTS AND METHODS: The Mayo Clinic amyloid database was queried for all patients with AL seen at the Mayo Clinic from 1983 through 1997 who would have been eligible for peripheral-blood stem-cell transplantation. Inclusion criteria included biopsy-proven amyloid, symptomatic disease, absence of a clinical diagnosis of multiple myeloma, age ≤ 70 years, cardiac interventricular septal thickness ≤ 15 mm, cardiac ejection fraction more than 55%, serum creatinine ≤ 2 mg/dL, and direct bilirubin ≤ 2.0 mg/dL. RESULTS: Median age was 56 years (range, 25 to 70) with 79 (34%) older than 60 years. One hundred patients had early cardiac involvement; 41, hepatic involvement; 167, renal involvement; and 39, nerve involvement. The 229 patients have had a median follow-up of 52 months, and 151 have died. The median survival was 42 months with 5- and 10-year survival rates of 36% and 15%, respectively. Important predictors of survival were size of M-component in 24-hour urine, number of involved organs, alkaline phosphatase, performance score, and weight loss. CONCLUSION: The same patients who are eligible for HSCT are a good-risk population who do relatively well with chemotherapy (median survival, 42 months), substantially better than the expected median survival of 18 months for all patients with AL. A randomized trial is needed to assess the true effect of HSCT.
Cancer-Related Fatigue: Prevalence of Proposed Diagnostic Criteria in a United States Sample of Cancer Survivors
Authors: Cella David , Davis Kimberly , Breitbart William , Curt Gregory ,   for the Fatigue Coalition
Published: February 2017

PURPOSE: To evaluate the proposed cancer-related fatigue (CRF) diagnostic criteria in a sample of cancer survivors. More accurate prevalence estimates of CRF may result in improved diagnosis and management of one of the most common symptoms associated with cancer and its treatment. METHODS: Three hundred seventy-nine individuals who had been treated with chemotherapy, either alone or in combination with radiation therapy, were surveyed. Patients were asked background questions about their current condition, their medical history, and the frequency of fatigue during their chemotherapy. Additionally, patients who reported experiencing fatigue at least a few days each month during treatment were asked a series of questions about the impact of fatigue on their daily functioning. RESULTS: One hundred forty-one (37%) individuals reported at least 2 weeks of fatigue in the previous month. Of the respondents who had received their last treatment more than 5 years ago, 33% still reported at least a 2-week period of fatigue in the month before the interview. Evaluation of the proposed criteria revealed that 17% of respondents met at least two criteria for CRF. CONCLUSION: The prevalence of diagnosable CRF in the individuals in this sample, most of whom had completed treatment more than 1 year ago, was 17%—lower than expected based on previous reports that have used less-strict criteria. In a sizable number of people, CRF persists well beyond active treatment and should be a focus of intervention. Although they will require replication in other samples and clinical validation, these formal diagnostic criteria can be a step toward common language and a better understanding of the severity range and persistence of CRF.
Funding New Cancer Drugs in Ontario: Closing the Loop in the Practice Guidelines Development Cycle
Authors: Pater J. L. , Browman G. P. , Brouwers M. C. , Nefsky M. F. , Evans W. K. , Cowan D. H. 
Published: February 2017

PURPOSE: The previously described practice guidelines development cycle follows an iterative model in which recommendations are reached by a process that incorporates practitioners at all phases. A key feature is the separation of the evidence-based systematic review and the generation of recommendations from policy decisions surrounding implementation. This article describes how this implementation phase has evolved in Ontario and how implementation has affected the guidelines process. METHODS: The development of the New Drug Funding Program in Ontario and the appointment of a policy advisory committee (PAC) to make funding recommendations were reviewed. The decision-making framework of the PAC is described in this article. RESULTS: The PAC has had to address a number of issues in making funding recommendations. These issues have included dealing with evidence arising solely from phase II versus phase III trials, using economic information, and involving community representatives in its deliberations. Its activities have had a substantial impact on the practice guidelines initiative. CONCLUSION: It is possible to integrate an evidence-based, practitioner-driven approach to clinical guideline development with a funding program that takes policy considerations into account. However, even though these two roles are conceptually separate, the needs of the funding program have inevitably had an impact on the guidelines process.
Intellectual Outcome After Reduced-Dose Radiation Therapy Plus Adjuvant Chemotherapy for Medulloblastoma: A Children’s Cancer Group Study
Authors: Ris M. Douglas , Packer Roger , Goldwein Joel , Jones-Wallace Dana , Boyett James M. 
Published: February 2017

PURPOSE: To investigate the intellectual outcomes of children with medulloblastomas/primitive neuroectodermal tumors (MB/PNET) treated with reduced-dose craniospinal radiotherapy (RT) plus adjuvant chemotherapy. PATIENTS AND METHODS: Forty-three children with average-risk posterior fossa MB/PNETs underwent longitudinal intelligence testing. All had been treated with a reduced-dose craniospinal RT regimen (23.4 Gy to the neuraxis, 32.4-Gy boost to the posterior fossa) and adjuvant chemotherapy. RESULTS: The estimated rate of change from baseline was significant for Full Scale Intelligence Quotient (FSIQ), Verbal IQ (VIQ), and Nonverbal IQ (NVIQ) (P < .001 for all three outcomes). The rate of change was estimated to be −4.3 FSIQ points per year, −4.2 VIQ points per year, and −4.0 NVIQ points per year. Females were more subject to VIQ decline than were males (P = .008), and young children (< 7 years of age) were more negatively affected than were older children, with a significant decline in NVIQ (P = .016). Finally, patients with higher baseline evaluations suffered greater declines in IQ than did those with lower baseline scores. CONCLUSION: This study represents the largest series of patients with average-risk MB/PNETs treated with a combination of reduced-dose RT and adjuvant chemotherapy whose intellectual development has been followed prospectively. Intellectual loss was substantial but suggestive of some degree of intellectual preservation compared with effects associated with conventional RT doses. However, this conclusion remains provisional, pending further research.