bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Trial of Murine 131I-Labeled Antitenascin Monoclonal Antibody 81C6 Administered Into Surgically Created Resection Cavities of Patients With Newly Diagnosed Malignant Gliomas
Authors: Reardon David A. , Akabani Gamal , Edward Coleman R. , Friedman Allan H. , Friedman Henry S. , Herndon James E. , Cokgor Ilkcan , McLendon Roger E. , Pegram Charles N. , Provenzale James M. , Quinn Jennifer A. , Rich Jeremy N. , Regalado Lorna V. , Sampson John H. , Shafman Timothy D. , Wikstrand Carol J. , Wong Terence Z. , Zhao Xiao-Guang , Zalutsky Michael R. , Bigner Darell D. 
Published: February 2017

PURPOSE: To assess the efficacy and toxicity of intraresection cavity 131I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: In this phase II trial, 120 mCi of 131I-labeled murine 81C6 was injected directly into the surgically created resection cavity of 33 patients with previously untreated malignant glioma (glioblastoma multiforme [GBM], n = 27; anaplastic astrocytoma, n = 4; anaplastic oligodendroglioma, n = 2). Patients then received conventional external-beam radiotherapy followed by a year of alkylator-based chemotherapy. RESULTS: Median survival for all patients and those with GBM was 86.7 and 79.4 weeks, respectively. Eleven patients remain alive at a median follow-up of 93 weeks (range, 49 to 220 weeks). Nine patients (27%) developed reversible hematologic toxicity, and histologically confirmed, treatment-related neurologic toxicity occurred in five patients (15%). One patient (3%) required reoperation for radionecrosis. CONCLUSION: Median survival achieved with 131I-labeled 81C6 exceeds that of historical controls treated with conventional radiotherapy and chemotherapy, even after accounting for established prognostic factors including age and Karnofsky performance status. The median survival achieved with 131I-labeled 81C6 compares favorably with either 125I interstitial brachy-therapy or stereotactic radiosurgery and is associated with a significantly lower rate of reoperation for radionecrosis. Our results confirm the efficacy of 131I-labeled 81C6 for patients with newly diagnosed malignant glioma and suggest that a randomized phase III study is indicated.
Neoadjuvant Chemotherapy in Breast Cancer: Significantly Enhanced Response With Docetaxel
Authors: Smith Ian C. , Heys Steven D. , Hutcheon Andrew W. , Miller Iain D. , Payne Simon , Gilbert Fiona J. , Ah-See Antoinne K. , Eremin Oleg , Walker Leslie G. , Sarkar Tarun K. , Eggleton S. Peter , Ogston Keith N. 
Published: February 2017

PURPOSE: To compare the efficacy of neoadjuvant (NA) docetaxel (DOC) with anthracycline-based therapy and determine the efficacy of NA DOC in patients with breast cancer initially failing to respond to anthracycline-based NA chemotherapy (CT). PATIENTS AND METHODS: Patients with large or locally advanced breast cancer received four pulses of cyclophosphamide 1,000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2, and prednisolone 40 mg (4 × CVAP) for 5 days. Clinical tumor response was assessed. Those who responded (complete response [CR] or partial response [PR]) were randomized to receive further 4 × CVAP or 4 × DOC (100 mg/m2). All nonresponders received 4 × DOC. RESULTS: One hundred sixty-two patients were enrolled; 145 patients completed eight cycles of NA CT. One hundred two patients (66%) achieved a clinical response (PR or CR) after 4 × CVAP. After randomization, 50 patients received 4 × CVAP and 47 patients received 4 × DOC. In patients who received eight cycles of CT, the clinical CR (cCR) and clinical PR (cPR) (94% v 66%) and pathologic CR (pCR) (34% v 16%) response rates were higher (P = .001 and P = .04) in those who received further DOC. Intention-to-treat analysis demonstrated cCR and cPR (85% v 64%; P = .03) and pCR (31% v 15%; P = .06). Axillary lymph node examination revealed residual tumor in 33% of patients who received 8 × CVAP and 38% of patients who received further DOC. In patients who failed to respond to the initial CVAP, 4 × DOC resulted in a cCR and cPR rate of 55% and a pCR rate of 2%. Forty-four percent of these patients had residual tumor within axillary lymph nodes. CONCLUSION: NA DOC resulted in substantial improvement in responses to DOC.
Effect of Graded Testicular Doses of Radiotherapy in Patients Treated for Carcinoma-In-Situ in the Testis
Authors: Petersen Peter Meidahl , Giwercman Aleksander , Daugaard Gedske , Rørth Mikael , Petersen Jørgen Holm , Skakkebæk Niels E. , Hansen Steen W. , von der Maase Hans 
Published: February 2017

PURPOSE: To determine the effect of radiotherapy in doses 14 to 20 Gy on eradication of carcinoma-in-situ (CIS) testis and on the Leydig cell function. PATIENTS AND METHODS: Forty-eight patients presented with unilateral testicular germ cell cancer and CIS of the contralateral testis. The CIS-bearing testis was treated with daily irradiation doses of 2 Gy, 5 days a week, to a cumulative dose of 20 Gy (21 patients), 18 Gy (three patients), 16 Gy (10 patients), and 14 Gy (14 patients). RESULTS: All patients treated at dose levels 20 Gy to 16 Gy achieved histologically verified complete remission without signs of recurrence of CIS after an observation period of more than 5 years. One of 14 patients treated at dose level 14 Gy had a relapse of CIS 20 months after irradiation. Leydig cell function was examined before and regularly after radiotherapy in 44 of 48 patients. The levels of testosterone were lower after radiotherapy than before. Testosterone showed a stable decrease for more than 5 years after treatment (3.6% per year) without dose dependency. The levels of luteinizing hormone and follicle-stimulating hormone were increased after radiotherapy. The need of androgen substitution therapy was similar at all dose levels. CONCLUSION: Testicular irradiation is a safe treatment at dose level 20 Gy (10 × 2 Gy). Decrease of dose to 14 Gy (7 × 2 Gy) might lead to risk of relapse of CIS. Impairment of hormone production without clinically significant dose dependency is seen in the dose range 14 to 20 Gy.
Phase III Evaluation of Fluoxetine for Treatment of Hot Flashes
Authors: Loprinzi Charles L. , Sloan Jeff A. , Perez Edith A. , Quella Susan K. , Stella Phillip J. , Mailliard James A. , Halyard Michele Y. , Pruthi Sandhya , Novotny Paul J. , Rummans Teresa A. 
Published: February 2017

PURPOSE: Hot flashes can be a prominent problem in women with a history of breast cancer. Given concerns regarding the use of hormonal therapies in such patients, other nonhormonal means for treating hot flashes are required. Based on anecdotal information regarding the efficacy of fluoxetine and other newer antidepressants for treating hot flashes, the present trial was developed. PATIENTS AND METHODS: This trial used a double-blinded, randomized, two-period (4 weeks per period), cross-over methodology to study the efficacy of fluoxetine (20 mg/d) for treating hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen (because of breast cancer risk). Eligible patients had to have reported that they averaged at least 14 hot flashes per week; they could have received tamoxifen or raloxifene as long as they were on a stable dose. The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score, analyzed by a classic sums and differences cross-over analysis. RESULTS: Eighty-one randomized women began protocol therapy. By the end of the first treatment period, hot flash scores (frequency × average severity) decreased 50% in the fluoxetine arm versus 36% in the placebo arm. Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo (P = .02). The results were not adjusted for potential confounding influences, including age and tamoxifen use. The fluoxetine was well tolerated. CONCLUSION: This dose of fluoxetine resulted in a modest improvement in hot flashes.
Prognostic Factors for Malignant Transformation in Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma
Authors: Cesana Clara , Klersy Catherine , Barbarano Luciana , Nosari Anna Maria , Crugnola Monica , Pungolino Ester , Gargantini Livio , Granata Simonetta , Valentini Marina , Morra Enrica 
Published: February 2017

PURPOSE: To evaluate the natural history of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), identify early predictors of evolution, and assess whether associated conditions correlate with disease progression. PATIENTS AND METHODS: A total of 1,231 consecutive patients with either MGUS (n = 1,104) or SMM (n = 127) diagnosed from July 1975 to March 1998 were included in the study. Cumulative survival probability and cumulative probability of transformation into lymphoproliferative disease were calculated by means of the Kaplan-Meier estimator. Univariate and multivariate Cox models were used to identify possible predictors of malignant evolution. RESULTS: Cumulative transformation probability at 10 and 15 years was 14% and 30%, respectively. At a median follow-up of 65 months (range, 12 to 239 months), 64 MGUS cases (5.8%) evolved to multiple myeloma (MM) (n = 43), extramedullary plasmacytoma (n = 1), primary amyloidosis (n = 1), Waldenström’s macroglobulinemia (n = 12), non-Hodgkin’s lymphoma (n = 6), and B-chronic lymphocytic leukemia (n = 1). At a median follow-up of 72 months (range, 12 to 247 months), 25 SMMs (19.7%) evolved to overt MM. A lower evolution risk was observed in MGUS than in SMM (P < .0001). Greater than 5% marrow plasmacytosis, detectable Bence Jones proteinuria, polyclonal serum immunoglobulin reduction, and high erythrocyte sedimentation rate (ESR) were independent factors influencing MGUS transformation. SMM progression correlated with greater than 10% marrow plasma cells, detectable Bence Jones proteinuria, and immunoglobulin (Ig) A isotype. Neither concomitant diseases nor immunosuppression correlated with progression. CONCLUSION: Careful evaluation of marrow plasmacytosis, urinary paraprotein, background immunoglobulins, ESR, and paraprotein isotype might help identify at presentation patients with benign monoclonal gammopathies requiring stricter monitoring.
Hepatic Drug Targeting: Phase I Evaluation of Polymer-Bound Doxorubicin
Authors: Seymour Leonard W. , Ferry David R. , Anderson David , Hesslewood Stuart , Julyan Peter J. , Poyner Richard , Doran Jayne , Young Annie M. , Burtles Sally , Kerr David J. 
Published: February 2017

PURPOSE: Preclinical studies have shown good anticancer activity following targeting of a polymer bearing doxorubicin with galactosamine (PK2) to the liver. The present phase I study was devised to determine the toxicity, pharmacokinetic profile, and targeting capability of PK2.PATIENTS AND METHODS: Doxorubicin was linked via a lysosomally degradable tetrapeptide sequence to N-(2-hydroxypropyl)methacrylamide copolymers bearing galactosamine. Targeting, toxicity, and efficacy were evaluated in 31 patients with primary (n = 25) or metastatic (n = 6) liver cancer. Body distribution of the radiolabelled polymer conjugate was assessed using gamma-camera imaging and single-photon emission computed tomography.RESULTS: The polymer was administered by intravenous (IV) infusion over 1 hour, repeated every 3 weeks. Dose escalation proceeded from 20 to 160 mg/m2(doxorubicin equivalents), the maximum-tolerated dose, which was associated with severe fatigue, grade 4 neutropenia, and grade 3 mucositis. Twenty-four hours after administration, 16.9% ± 3.9% of the administered dose of doxorubicin targeted to the liver and 3.3% ± 5.6% of dose was delivered to tumor. Doxorubicin-polymer conjugate without galactosamine showed no targeting. Three hepatoma patients showed partial responses, with one in continuing partial remission 47 months after therapy.CONCLUSION: The recommended PK2 dose is 120 mg/m2, administered every 3 weeks by IV infusion. Liver-specific doxorubicin delivery is achievable using galactosamine-modified polymers, and targeting is also seen in primary hepatocellular tumors.
Doxorubicin Administration by Continuous Infusion Is Not Cardioprotective: The Dana-Farber 91-01 Acute Lymphoblastic Leukemia Protocol
Authors: Lipshultz Steven E. , Giantris Amy L. , Lipsitz Stuart R. , Dalton Virginia Kimball , Asselin Barbara L. , Barr Ronald D. , Clavell Luis A. , Hurwitz Craig A. , Moghrabi Albert , Samson Yvan , Schorin Marshall A. , Gelber Richard D. , Sallan Stephen E. , Colan Steven D. 
Published: February 2017

PURPOSE: Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug, but mechanisms of cardiotoxicity are different in children. We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin. PATIENTS AND METHODS: In a randomized study, children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m2 in 30-mg/m2 doses every 3 weeks either by bolus (within 1 hour, n = 57) or by continuous infusion (over 48 hours, n = 64). Echocardiograms obtained before doxorubicin and at longest follow-up times were centrally remeasured, and z scores of cardiac measurements were calculated based on a healthy population. RESULTS: The groups were similar in age, sex distribution, doxorubicin dose, and duration of follow-up. Before treatment, measures of left ventricular (LV) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups. The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic, but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline. For example, the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms. LV contractility was depressed in both groups (for bolus patients, median z score = −0.70 SD, P = .006; for continuous-infusion patients, median z score = −0.765, P = .005). Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups. Clinical cardiac manifestations and event-free survival did not differ. CONCLUSION: Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion. Both regimens were associated with progressive subclinical cardiotoxicity. Other cardioprotective strategies should be explored.
Intergroup randomized phase III study of androgen deprivation therapy (ADT) plus radiation therapy (RT) in locally advanced prostate cancer (CaP) (NCIC-CTG, SWOG, MRC-UK, INT: T94-0110; NCT00002633).
Authors: Warde P. R. , Mason M. D. , Sydes M. R. , Gospodarowicz M. K. , Swanson G. P. , Kirkbride P. , Kostashuk E. , Hetherington J. , Ding K. , Parulekar W. ,   NCIC CTG PR.3/MRC PRO7/SWOG JPR3 Investigators
Published: February 2017

CRA4504 Background: The impact of radiotherapy on overall survival (OS) in men with locally advanced CaP is unclear. The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality. Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. Methods: Patients with T3/T4 (1057) or T2, PSA > 40 μ g/l (119) or T2 PSA > 20 μ g/l and Gleason ≥ 8 (25) and N0 /NX, M0 prostate adenocarcinoma were randomized to lifelong ADT (bilateral orchiectomy or LHRH agonist) with or without RT (65-69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes). The primary endpoint was OS and secondary endpoints included disease specific survival (DSS), time to disease progression and quality of life. Results: 1205 patients were randomized from 1995 to 2005, 602 to ADT and 603 to ADT+RT (well balanced with respect to baseline characteristics). A protocol specified second interim analysis on OS was performed in Aug 2009 (data cut-off Dec 31 2008). The DSMC recommended release of the results to the Trial Committee for publication. The median follow-up is 6.0 years and 320 patients have died (175 ADT and 145 ADT+RT). 10% of patients had no follow-up data beyond 2006. The addition of RT to ADT significantly reduced the risk of death (hazard ratio [HR] 0.77, 95% CI 0.61-0.98, p=0.033). 140 patients died of disease and/or treatment (89 on ADT and 51 on ADT+RT) The disease specific survival HR was 0.57 (95% CI 0.41-0.81, p=0.001) favoring ADT+RT. The 10 year cumulative disease specific death rates were estimated at 15% with ADT+ RT and 23% with ADT alone. Grade ≥2 late GI toxicity rates were similar in both arms (proctitis, 1.3% ADT alone, 1.8% ADT+RT). Conclusions: The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach (ADT+RT) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity. In view of this data combined modality therapy (ADT+RT) should be the standard treatment approach for these patients. Supported by NCI-US Grant #5U10CA077202-12, CCSRI Grant #15469. No significant financial relationships to disclose.
Phase III trial of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC).
Authors: Crown J. , Dieras V. , Staroslawska E. , Yardley D. A. , Davidson N. , Bachelot T. D. , Tassell V. R. , Huang X. , Kern K. A. , Romieu G. 
Published: February 2017

LBA1011 Background: Recent trials support combining an antiangiogenic agent with chemotherapy (CT) in pretreated patients (pts) with metastatic BC (MBC). SU, an oral multitargeted tyrosine kinase inhibitor demonstrated single-agent activity (11% ORR) in heavily pretreated pts with MBC. Antitumor activity with SU+C was reported in pts with advanced solid tumors. This multicenter, randomized, phase III trial (SUN 1099) compared the efficacy and safety of SU + C vs. C in pts with ABC. Methods: Eligibility criteria were: age ≥18 yrs, ECOG PS ≤1, measurable HER2-positive (FISH+, CISH+ or IHC3+) or -negative ABC, no brain metastases, prior treatment (tx) with an anthracycline and taxane in the (neo)adjuvant or metastatic setting, and ≤2 prior CT regimens for advanced disease. Prior C tx was not permitted. Pts were randomized (1:1) to combination tx with C 2,000 mg/m2/d po days 1–14 every q3w + SU 37.5 mg/d po daily, or to C 2,500 mg/m2/d days 1–14 q3w. Pts with progressive disease per RECIST on the C arm were offered single-agent SU (37.5 mg/d). Endpoints included PFS (primary), ORR, OS, QoL, and safety. Stratified and unstratified log-rank tests compared PFS between arms. Results: At the data cutoff (December 15, 2009), the ITT population comprised 442 pts: 221 in each arm with baseline characteristics well balanced between arms. The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment nor secondary endpoint of longer OS (final analysis March 10, 2010). Median PFS was 5.5 mos (95% CI 4.5–6.0) in the SU+C arm vs. 5.9 mos (95% CI 5.4–7.6) in the C arm (HR 1.224). Median OS was 16.4 mos (95% CI 13.6–18.4) for the SU+C arm and 16.5 mos (95% CI 14.2–18.6) for the C arm (HR 0.995). ORR was 18.6% for the SU+C arm and 16.3% for the C arm. The most common all causality grade 3/4 AEs (≥10%) were neutropenia (32%), hand–foot syndrome (HFS; 16%), thrombocytopenia (17%), asthenia (12%), fatigue (10%) in the SU+C arm and HFS (24%) and diarrhea (10%) in the C arm. Intended drug delivery for each arm was >80%. Discontinuations due to an AE were more frequent in the SU+C arm vs. the C arm. Discontinuations by drug in the SU+C arm: SU 39%, C 42%, SU and C 33%; in the C arm: 18%. Conclusions: Data from this randomized phase III trial do not support use of SU+C for therapy of patients with ABC. [Table: see text]
A prospective, randomized, open-label, phase III clinical trial of NovoTTF-100A versus best standard of care chemotherapy in patients with recurrent glioblastoma.
Authors: Stupp R. , Kanner A. , Engelhard H. , Heidecke V. , Taillibert S. , Lieberman F. S. , Dbalý V. , Kirson E. D. , Palti Y. , Gutin P. H. 
Published: February 2017

LBA2007 Background: The NovoTTF is a portable, medical device delivering low intensity, intermediate frequency, alternating electric fields by means of noninvasive, disposable scalp electrodes. These tumor treatment fields (TTF) physically interfere with cell division and assembly of organelles. Methods: Adult pts (KPS≥70%) with recurrent GBM were randomized (stratified by surgery for recurrence and center) to either NovoTTF administered continuously (20-24h/day, 7 days/week) or the best standard chemotherapy (BSC) at each physicians’ discretion. Number of prior therapies was not limited. Primary endpoint was overall survival (OS). The study was powered (80%) to detect a 60% increase in OS with a two tailed a of 0.05. Results: 237 pts were randomized (28 centers in the United States and Europe) to either TTF alone (120 pts) or BSC (117 pts). Patient characteristics were balanced, median age was 54 years (range 23-80), median KPS 80% (50-100). All had prior TMZ/RT, and the majority at least one prior therapy for recurrence. One-quarter had surgery for recurrence. Mean treatment duration was 4.4 mo (0-40) vs. 2.3 mo (0-15), median OS was 6.6 vs. 6.0 months for TTF and BSC, respectively (p=0.23, hazard ratio 0.84 [95% CI 0.63-1.12]), the 1-year survival rate 23.6% versus 20.8% (ns). PFS6 was 17.6% in both groups. Time to treatment failure favored the TTF group (HR 0.76 [0.57-1.02], p=0.07). Objective responses were more common in the TTF arm (12%) versus the BSC (6%). Related adverse events were mild-to-moderate skin rash beneath the electrodes in 17% of TTF treated pts. Hematological and other toxicities were observed at a significantly higher incidence in the BSC arm depending on the type of chemotherapy, no treatment-related deaths occurred. Treatment compliance with TTF was excellent with a median duration 20 hours/day. Conclusions: This is the first phase III, controlled clinical trial testing TTF, an entirely novel treatment modality. TTF had minimal toxicity, long-term treatment proved feasible. TTF as a single modality showed a higher response rate and longer time to treatment failure compared to best available chemotherapy. Overall survival also favored TTF, but did not reach statistical significance. In view of the above, TTF should be considered a valid novel treatment modality. [Table: see text]