bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paclitaxel Versus Doxorubicin as First-Line Single-Agent Chemotherapy for Metastatic Breast Cancer: A European Organization for Research and Treatment of Cancer Randomized Study With Cross-Over
Authors: Paridaens R. , Biganzoli L. , Bruning P. , Klijn J.G. M. , Gamucci T. , Houston S. , Coleman R. , Schachter J. , Van Vreckem A. , Sylvester R. , Awada A. , Wildiers J. , Piccart M. ,   on behalf of the European Organization for Research and Treatment of Cancer-Investigational Drug Branch for Breast Cancer/Early Clinical Studies Group
Published: February 2017

PURPOSE: To compare the efficacy of paclitaxel versus doxorubicin given as single agents in first-line therapy of advanced breast cancer (primary end point, progression-free survival [PFS]) and to explore the degree of cross-resistance between the two agents. PATIENTS AND METHODS: Three hundred thirty-one patients were randomized to receive either paclitaxel 200 mg/m2, 3-hour infusion every 3 weeks, or doxorubicin 75 mg/m2, intravenous bolus every 3 weeks. Seven courses were planned unless progression or unacceptable toxicity occurred before the seven courses were finished. Patients who progressed within the seven courses underwent early cross-over to the alternative drug, while a delayed cross-over was optional for the remainder of patients at the time of disease progression. RESULTS: Objective response in first-line therapy was significantly better (P = .003) for doxorubicin (response rate [RR], 41%) than for paclitaxel (RR, 25%), with doxorubicin achieving a longer median PFS (7.5 months for doxorubicin v 3.9 months for paclitaxel, P < .001). In second-line therapy, cross-over to doxorubicin (91 patients) and to paclitaxel (77 patients) gave response rates of 30% and 16%, respectively. The median survival durations of 18.3 months for doxorubicin and 15.6 months for paclitaxel were not significantly different (P = .38). The doxorubicin arm had greater toxicity, but this was counterbalanced by better symptom control. CONCLUSION: At the dosages and schedules used in the present study, doxorubicin achieves better disease and symptom control than paclitaxel in first-line treatment. Doxorubicin and paclitaxel are not totally cross-resistant, which supports further investigation of these drugs in combination or in sequence, both in advanced disease and in the adjuvant setting.
Racial Differences in the Survival of Childhood B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study
Authors: Pollock Brad H. , DeBaun Michael R. , Camitta Bruce M. , Shuster Jonathan J. , Ravindranath Yaddanapudi , Pullen D. Jeanette , Land Vita J. , Mahoney Donald H. , Lauer Stephen J. , Murphy Sharon B. 
Published: February 2017

PURPOSE: We conducted a historic cohort study to test the hypothesis that, after adjustment for biologic factors, African-American (AA) children and Spanish surname (SS) children with newly diagnosed B-precursor acute lymphoblastic leukemia had lower survival than did comparable white children. PATIENTS AND METHODS: From 1981 to 1994, 4,061 white, 518 AA, and 507 SS children aged 1 to 20 years were treated on three successive Pediatric Oncology Group multicenter randomized clinical trials. RESULTS: AA and SS patients were more likely to have adverse prognostic features at diagnosis and lower survival than were white patients. The 5-year cumulative survival rates were (probability ± SE) 81.9% ± 0.6%, 68.6% ± 2.1%, and 74.9% ± 2.0% for white, AA, and SS children, respectively. Adjusting for age, leukocyte count, sex, era of treatment, and leukemia blast cell ploidy, we found that AA children had a 42% excess mortality rate compared with white children (proportional hazards ratio [PHR] = 1.42; 95% confidence interval [CI], 1.12 to 1.80), and SS children had a 33% excess mortality rate compared with white children (PHR = 1.33; 95% CI, 1.19 to 1.49). CONCLUSION: Clinical presentation, tumor biology, and deviations from prescribed therapy did not explain the differences in survival and event-free survival that we observed, although differences seem to be diminishing over time with improvements in therapy. The disparity in outcome for AA and SS children is most likely related to variations in chemotherapeutic response to therapy and not to compliance. Further improvements in outcome may require individualized dosing based on specific pharmacogenetic profiles, especially for AA and SS children.
Phase I Studies of Anti–Epidermal Growth Factor Receptor Chimeric Antibody C225 Alone and in Combination With Cisplatin
Authors: Baselga J. , Pfister D. , Cooper M.R. , Cohen R. , Burtness B. , Bos M. , D’Andrea G. , Seidman A. , Norton L. , Gunnett K. , Falcey J. , Anderson V. , Waksal H. , Mendelsohn J. 
Published: February 2017

PURPOSE: The epidermal growth factor (EGF) receptor is frequently overexpressed in epithelial tumors. C225 is a human-to-murine chimeric monoclonal antibody that binds to the receptor and inhibits growth of cancer cells expressing the receptor. We evaluated the pharmacokinetics and toxicity of C225 in patients with advanced tumors overexpressing EGF receptors. PATIENTS AND METHODS: We treated 52 patients in three successive phase I clinical trials of C225 as a single dose (n = 13), weekly multiple dose (n = 17), and weekly multiple dose with cisplatin (n = 22). C225 dose levels were 5, 20, 50, and 100 mg/m2. In the study combining C225 with cisplatin, limited to patients with either head and neck or non–small-cell lung cancer, C225 was further escalated to 200 and 400 mg/m2. Cisplatin was given at a dose of 60 mg/m2 once every 4 weeks, and treatment was continued for up to 12 weeks if no disease progression occurred. RESULTS: C225 displayed nonlinear pharmacokinetics, with antibody doses in the range of 200 to 400 mg/m2 being associated with complete saturation of systemic clearance. C225 clearance did not change with repeated administration or with coadministration of cisplatin. Antibodies against C225 were detected in only one patient, and C225-associated toxicity was minimal. Patients experiencing disease stabilization were seen in all studies. In the study combining C225 and cisplatin, nine (69%) of 13 patients treated with antibody doses ≥ 50 mg/m2 completed 12 weeks of therapy, and two partial responses were observed. CONCLUSION: C225 has dose-dependent pharmacokinetics, and doses that achieve saturation of systemic clearance are well tolerated. C225 given in combination with cisplatin has biologic activity at pharmacologically relevant doses.
Cognitive and Academic Functioning in Survivors of Pediatric Bone Marrow Transplantation
Authors: Phipps Sean , Dunavant Maggi , Srivastava Deo K. , Bowman Laura , Mulhern Raymond K. 
Published: February 2017

PURPOSE: To evaluate cognitive and academic functioning in survivors of pediatric bone marrow transplants (BMTs) at 1 and 3 years after a BMT. PATIENTS AND METHODS: In a prospective, longitudinal design, patients underwent a comprehensive battery of neurocognitive measures before admission for transplantation and at 1, 3, and 5 years after a BMT. This article describes a cohort of 102 survivors with follow-up data available for 1 year after a BMT, including 54 survivors with follow-up available for 3 years. This represents the largest cohort of pediatric BMT survivors yet reported in a prospective study. RESULTS: In the cohort as a whole, there were no significant changes on global measures of intelligence (intelligence quotient [IQ]) and academic achievement at either 1 or 3 years after a BMT, despite adequate power to detect an IQ change of three points or greater. Likewise, performance on specific tests of neuropsychologic function remained stable. No significant differences were observed between patients whose conditioning regimen included total-body irradiation (TBI) and those whose did not. The primary predictor of neurocognitive outcome was patient age, with younger patients more likely to show declines over time. The subset of patients who were less than 3 years of age at the time of transplantation seemed to be particularly vulnerable to cognitive sequelae. CONCLUSION: The use of BMTs with or without TBI entails minimal risk of late neurocognitive sequelae in patients who are 6 years of age or older at the time of transplantation. However, patients who are less than 6 years of age at the time of transplantation, and particularly those less than 3 years of age, seem to be at some risk of cognitive declines.
TrkC Expression Predicts Good Clinical Outcome in Primitive Neuroectodermal Brain Tumors
Authors: Grotzer M.A. , Janss A.J. , Fung K.-M. , Biegel J.A. , Sutton L.N. , Rorke L.B. , Zhao H. , Cnaan A. , Phillips P.C. , Lee V.M.-Y. , Trojanowski J.Q. 
Published: February 2017

PURPOSE: To identify biologic prognostic factors in childhood primitive neuroectodermal tumors (PNET), including medulloblastoma, that accurately define patient groups with sufficiently good prognosis to permit a reduction in treatment intensity. PATIENTS AND METHODS: We determined expression levels of the neurotrophin receptor TrkC mRNA in formalin-fixed tumor samples from 87 well characterized PNET patients using in situ hybridization. Comparison of TrkC mRNA expression levels with clinical and other laboratory variables was performed using univariate and multivariate Cox regression analysis. RESULTS: High TrkC mRNA expression was found to be associated more with higher 5-year cumulative survival rate than was low TrkC mRNA expression (89% v 46%, respectively). When compared with established clinical prognostic factors and laboratory variables of potential prognostic significance, TrkC mRNA expression, by univariate analysis, was found to be the single most powerful predictor of outcome (hazards ratio, 4.81; P < .00005), exceeding all clinical prognostic factors. In multivariate analysis, the hazards ratio remained significant (P < .00005). CONCLUSION: High TrkC mRNA expression in PNET is a powerful independent predictor of favorable clinical outcome. Assessment of TrkC mRNA levels may aid in treatment planning for patients with PNETs and should be incorporated prospectively into PNET clinical trials.
Topotecan Has Substantial Antitumor Activity as First-Line Salvage Therapy in Platinum-Sensitive Epithelial Ovarian Carcinoma: A Gynecologic Oncology Group Study
Authors: McGuire William P. , Blessing John A. , Bookman Michael A. , Lentz Samuel S. , Dunton Charles J. 
Published: February 2017

PURPOSE: Topotecan is known to be active in recurrent ovarian cancer, but most prior studies have focused on platinum-resistant or refractory populations. This study was undertaken to define the response rate and progression-free interval in platinum-sensitive patients. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after one or two prior chemotherapy regimens and in whom the interval between prior platinum therapy and the initiation of protocol therapy was greater than 6 months were treated with topotecan 1.5 mg/m2 intravenously over 30 minutes daily for 5 days, with this cycle repeated every 21 days. RESULTS: Forty-eight patients were entered onto the study; 47 were assessable for toxicity and 46 for response. The response rate was 33% (two complete responses and 13 partial responses), with a median response duration of 11.2 months. Hematologic toxicity predominated but was manageable in most patients with frequent incorporation of cytokines and RBC and platelet transfusions. Fatigue was reported in 15 patients and resulted in the discontinuation of therapy in five responding patients. CONCLUSION: Topotecan is an active drug in platinum-sensitive ovarian cancer, with significant but manageable hematologic toxicity. Fatigue is also a common problem that may be dose-limiting in some patients.
High Local Recurrence Risk After Breast-Conserving Therapy in Node-Negative Premenopausal Breast Cancer Patients Is Greatly Reduced by One Course of Perioperative Chemotherapy: A European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study
Authors: Elkhuizen Paula H. M. , van Slooten Henk-Jan , Clahsen Pieter C. , Hermans Jo , van de Velde Cornelis J. H. , van den Broek Lambert C. J. M. , van de Vijver Marc J. ,   Cooperating Investigators
Published: February 2017

PURPOSE: Patients with invasive breast cancer may develop a local recurrence (LR) after breast-conserving therapy (BCT). Younger age has been found to be an independent risk factor for LR. Within a group of premenopausal node-negative breast cancer patients, we studied risk factors for LR and the effect of perioperative chemotherapy (PeCT) on LR. PATIENTS AND METHODS: The European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial (EORTC 10854) to compare surgery followed by one course of PeCT (fluorouracil, doxorubicin, and cyclophosphamide) with surgery alone. From patients treated on this trial, we selected premenopausal patients with node-negative breast cancer who were treated with BCT to examine whether histologic characteristics and the expression of various proteins (estrogen receptor, progesterone receptor, p53, Ki-67, bcl-2, CD31, c-erbB-2/neu) are risk factors for subsequent LR. Also, the effect of one course of PeCT on the LR risk (LRR) was studied. RESULTS: Using multivariate analysis, age younger than 43 years (relative risk [RR], 2.75; 95% confidence interval [CI], 1.46 to 5.18; P = .002), multifocal growth (RR, 3.34; 95% CI, 1.27 to 8.77; P = .014), and elevated levels of p53 (RR, 2.14; 95% CI, 1.13 to 4.05; P = .02) were associated with higher LRR. Also, PeCT was found to reduce LRR by more than 50% (RR, 0.47; 95% CI, 0.25 to 0.86; P = .02). Patients younger than 43 years who received PeCT achieved similar LR rates as those of patients younger than 43 years who were treated with BCT alone. CONCLUSION: In premenopausal node-negative patients, age younger than 43 years is the most important risk factor for LR after BCT; this risk is greatly reduced by one course of PeCT. The main reason for administering systemic adjuvant treatment is to improve overall survival. The important reduction of LR after BCT is an additional reason for considering systemic treatment in young node-negative patients with breast cancer.
Prospective Analysis of Staphylococcus aureus Bacteremia in Nonneutropenic Adults With Malignancy
Authors: Gopal Ajay K. , Fowler Vance G. , Shah Manish , Gesty-Palmer Diane , Marr Kieren A. , McClelland R. Scott , Kong Li Kuo , Gottlieb Geoffrey S. , Lanclos Kevin , Li Jennifer , Sexton Daniel J. , Corey G. Ralph 
Published: February 2017

PURPOSE: To determine the primary sources and secondary complications of Staphylococcus aureus bacteremia (SAB) in cancer patients, as well as predictors of outcome in cancer patients with SAB.PATIENTS AND METHODS: Fifty-two patients at Duke University Medical Center met entry criteria between September 1994 and December 1996 for this prospective cohort study involving hospitalized nonneutropenic adult cancer patients with SAB. All subjects were observed throughout initial hospitalization and were evaluated again at 6 and 12 weeks or until death.RESULTS: SAB was intravascular device–related in 42%, tissue infection–related (TIR) in 44%, and unidentifiable focus–related (UFR) in 13%. Seventeen patients (33%) were found to have metastatic infections or conditions, with eight (15%) developing infectious endocarditis (IE). Patients with TIR bacteremia were less likely than other patients to develop IE (4% v 24%, P = .06). The overall mortality rate was 38%, the SAB-related mortality rate was 15%, and the rate of SAB relapse was 12%. Methicillin resistance was not associated with adverse outcome. Inability to identify a point of entry (UFR bacteremia), however, was associated with a higher overall mortality rate (100% v 24%, P = .0006). Furthermore, a 72-hour surveillance blood culture positive for organisms was associated with an increased incidence of IE (P = .0006), metastatic infections or conditions (P = .0002), SAB relapse (P = .038), and SAB-related death (P = .038).CONCLUSION: SAB in cancer patients is associated with significant morbidity from frequent metastatic infections or conditions including IE, as well as considerable mortality. Unknown initial infection site and 72-hour surveillance cultures positive for organisms were predictive of a complicated course and poor final outcome.
Assessment of the Stanford V Regimen and Consolidative Radiotherapy for Bulky and Advanced Hodgkin’s Disease: Eastern Cooperative Oncology Group Pilot Study E1492
Authors: Horning Sandra J. , Williams Jovanne , Bartlett Nancy L. , Bennett John M. , Hoppe Richard T. , Neuberg Donna , Cassileth Peter 
Published: February 2017

PURPOSE: This study was performed, in a multi-institutional setting, to evaluate the efficacy and feasibility of the Stanford V chemotherapy regimen plus radiotherapy to bulky Hodgkin’s disease sites. PATIENTS AND METHODS: A two-stage design was implemented in a phase II study involving 47 patients with bulky mediastinal stage I/II or stage III/IV Hodgkin’s disease. Twelve weeks of the Stanford V chemotherapy regimen were given with consolidative radiotherapy (36 Gy) to lymph nodes ≥ 5 cm and/or macroscopic splenic disease. Treatment was administered in one of five institutions participating in the Eastern Cooperative Oncology Group. RESULTS: With a median follow-up of 4.8 years, 45 patients are alive and 40 have been continuously disease-free. The estimated freedom from progression was 87% at 2 years and 85% at 5 years. Overall survival was 96% at 2 and 5 years. There was one death from Hodgkin’s disease and one death from an M5 acute leukemia. Six of seven relapsed patients received high-dose therapy and autologous stem-cell transplantation. The freedom from second progression for the seven relapsed patients was estimated at 98% at 3 years. CONCLUSION: Stanford V chemotherapy and consolidative radiotherapy to bulky disease is effective in bulky and advanced Hodgkin’s disease in a multi-institutional setting. On this basis, an Intergroup study comparing doxorubicin, bleomycin, vinblastine, and dacarbazine with the Stanford V regimen has been initiated.
Prospective Randomized Comparison of Single-Dose Versus Hyperfractionated Total-Body Irradiation in Patients With Hematologic Malignancies
Authors: Girinsky Theodore , Benhamou Ellen , Bourhis Jean-Henry , Dhermain Frederic , Guillot-Valls Dolores , Ganansia Valerie , Luboinski Monique , Perez Adriana , Cosset Jean Marc , Socie Gérard , Baume Daniel , Bouaouina Nourédine , Briot Edith , Beaudre Anne , Bridier André , Pico Jose Luis 
Published: February 2017

PURPOSE: Fractionated total-body irradiation (HTBI) is considered to induce less toxicity to normal tissues and probably has the same efficacy as single-dose total-body irradiation (STBI) in patients with acute myeloid leukemia. We decided to determine whether this concept can be applied to a large number of patients with various hematologic malignancies using two dissimilar fractionation schedules. PATIENTS AND METHODS: Between December 1986 and October 1994, 160 patients with various hematologic malignancies were randomized to receive either a 10-Gy dose of STBI or 14.85-Gy dose of HTBI. RESULTS: One hundred forty-seven patients were assessable. The 8-year overall survival rate and cause-specific survival rate in the STBI group was 38% and 63.5%, respectively. Overall survival rate and cause-specific survival rate in the HTBI group was 45% and 77%, respectively. The incidence of interstitial pneumonitis was similar in both groups. However, the incidence of veno-occlusive disease (VOD) of the liver was significantly higher in the STBI group. In the multivariate analysis with overall survival as the end point, the female sex was an independent favorable prognostic factor. On the other hand, when cause-specific survival was considered as the end point, the multivariate analysis demonstrated that sex and TBI were independent prognostic factors. CONCLUSION: The efficacy of HTBI is probably higher than that of STBI. Both regimens induce similar toxicity with the exception of VOD of the liver, the incidence of which is significantly more pronounced in the STBI group.
Docetaxel Administered on a Weekly Basis for Metastatic Breast Cancer
Authors: Burstein Harold J. , Manola Judith , Younger Jerry , Parker Leroy M. , Bunnell Craig A. , Scheib Rochelle , Matulonis Ursula A. , Garber Judy E. , Clarke Kathryn D. , Shulman Lawrence N. , Winer Eric P. 
Published: February 2017

PURPOSE: To evaluate the safety and efficacy of weekly docetaxel in women with metastatic breast cancer. PATIENTS AND METHODS: Twenty-nine women were enrolled onto a study of weekly docetaxel given at 40 mg/m2/wk. Each cycle consisted of 6 weeks of therapy followed by a 2-week treatment break, repeated until disease progression or removal from study for toxicity or patient preference. Fifty-two percent of patients had been previously treated with adjuvant chemotherapy; 21% had received prior chemotherapy for metastatic breast cancer, and 31% had previously received anthracyclines. All patients were assessable for toxicity; two patients were not assessable for response but are included in an intent-to-treat analysis. RESULTS: Patients received a median of 18 infusions, with a median cumulative docetaxel dose of 720 mg/m2. There were no complete responses. Twelve patients had partial responses (overall response rate, 41%; 95% confidence interval, 24% to 61%), all occurring within the first two cycles. Similar response rates were observed among subgroups of patients previously treated either with any prior chemotherapy or with anthracyclines. An additional 17% of patients had stable disease for at least 6 months. The regimen was generally well tolerated. There was no grade 4 toxicity. Only 28% of patients had any grade 3 toxicity, most commonly neutropenia and fatigue. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and eye tearing/conjunctivitis became more common with repetitive dosing, although these side effects rarely exceeded grade 2. Dose reductions were made for eight of 29 patients, most often because of fatigue (n = 5). CONCLUSION: Weekly docetaxel is active in treating patients with metastatic breast cancer, with a side effect profile that differs from every-3-weeks therapy.