bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of Cisplatin and Vinorelbine as First-Line Chemotherapy in Patients With Carcinoma of the Uterine Cervix
Authors: Pignata Sandro , Silvestro Giustino , Ferrari Ettore , Selvaggi Luigi , Perrone Francesco , Maffeo Antonio , Frezza Pasquale , Di Vagno Giovanni , Casella Gennaro , Ricchi Paolo , Cormio Gennaro , Gallo Ciro , Iodice Francesco , Romeo Frank , Fiorentino Roberto , Fortuna Giovanni , Tramontana Sergio 
Published: February 2017

PURPOSE: To evaluate the activity and toxicity of the combination of cisplatin (80 mg/m2 day 1) and vinorelbine (25 mg/m2 days 1 and 8) in patients with carcinoma of the uterine cervix that has not been previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients with cervical cancer were enrolled onto this study (27 stage IB-III, 23 stage IVB-recurrent). A two-stage optimal Simon design was applied. Thirteen responders of 29 treated patients were required to proceed beyond the first stage, and 28 responders were needed overall. RESULTS: Hematologic toxicity was mild, with neutropenia being the most frequent side effect. Nonhematologic toxicity was frequent but never severe; one patient had grade 3 peripheral neurotoxicity. Objective responses were recorded for 32 patients (64%): 11 patients (22%) achieved a complete response (CR) and 21 patients (42%) achieved a partial response (PR). The response rate was 81.5% in patients with IB-III stage (25.9% CR rate) and 43.5% in patients with IVB-recurrent disease (17.4% CR rate). Responses were seen both in stage IVB patients (one CR and two PRs, for an overall rate of 37.5%) and in patients with recurrent disease (three CRs + four PRs, for an overall rate of 46.7%). CONCLUSION: The combination of cisplatin and vinorelbine is an active regimen in the treatment of patients with early-stage and advanced carcinoma of the uterine cervix. The hematologic and nonhematologic toxicity of this combination is mild.
Sex Differences in Prognosis for Children With Acute Lymphoblastic Leukemia
Authors: Pui Ching-Hon , Boyett James M. , Relling Mary V. , Harrison Patricia L. , Rivera Gaston K. , Behm Frederick G. , Sandlund John T. , Ribeiro Raul C. , Rubnitz Jeffrey E. , Gajjar Amar , Evans William E. 
Published: February 2017

PURPOSE: Whether recent improvements in the treatment of childhood acute lymphoblastic leukemia (ALL) have nullified the adverse prognosis associated with male sex remains unclear. Therefore, we analyzed the survival experience and presenting clinical and laboratory features of boys and girls with newly diagnosed ALL who were treated at our institution over the past three decades. PATIENTS AND METHODS: One thousand one hundred fifty-one boys and 904 girls were treated in 13 consecutive Total Therapy studies between 1962 and 1994. An overview analysis was used to investigate the impact of sex on overall and event-free survival, both for the entire cohort and for subgroups defined by treatment era and blast-cell immunophenotype. Stratified analyses were performed to adjust for treatment protocol and known risk factors, and in the modern treatment era, for protocol, immunophenotype, and the DNA content of leukemic cells (ie, DNA index). The pharmacokinetics of methotrexate, teniposide, and cytarabine, as well as the thiopurine methyltransferase activity of erythrocytes, were compared between boys and girls treated on a single protocol. RESULTS: Compared with girls, boys were more likely to have T-cell ALL (20.9% v 10.7%, P < .001) and seemed less likely to have a favorable DNA index (17.8% v 25.1%, P = .072). There were no other statistically significant differences between the two sexes with respect to presenting features, including leukemic-cell genetic abnormalities, nor were there significant sex differences in the pharmacokinetics of methotrexate, teniposide, or cytarabine or in erythrocyte thiopurine methyltransferase activity. Girls clearly fared better than boys (P < .001) on protocols used during the early era of treatment (10-year event-free survival ± 1 SE, 43.1% ± 2.1% v 31.5% ± 1.7%). Although prognosis improved for both sexes in the modern era, the difference in outcome between girls and boys persisted (P = .025) (10-year event-free survival, 73.4% ± 3.7% v 63.5% ± 4.0%). However, stratification of modern-era patients by protocol, immunophenotype, and DNA index mitigated statistical evidence of a sex difference in overall survival (P = .263) and event-free survival (P = .124). CONCLUSION: Although boys and girls alike have benefited from improvements in ALL therapy, these gains have not completely eliminated the sex difference in prognosis that has persisted since the early 1960s. The apparent difference in outcome is partially explained by differences between boys and girls in the distributions of ALL immunophenotype and DNA index.
Combined Irinotecan and Oxaliplatin Plus Granulocyte Colony-Stimulating Factor in Patients With Advanced Fluoropyrimidine/Leucovorin-Pretreated Colorectal Cancer
Authors: Scheithauer Werner , Kornek Gabriela V. , Raderer Markus , Valencak Julia , Weinländer Georg , Hejna Michael , Haider Karin , Kwasny Werner , Depisch Dieter 
Published: February 2017

PURPOSE: To evaluate the efficacy and tolerance of combined irinotecan and oxaliplatin in patients with advanced colorectal cancer pretreated with leucovorin-modulated fluoropyrimidines. PATIENTS AND METHODS: Thirty-six patients with metastatic colorectal cancer, who progressed while receiving or within 6 months after discontinuing palliative chemotherapy with fluoropyrimidines/leucovorin, were enrolled onto this study. Treatment consisted of oxaliplatin 85 mg/m2 on days 1 + 15 and irinotecan 80 mg/m2 on days 1 + 8 + 15 every 4 weeks. Depending on the absolute neutrophil counts (ANC) on the day of scheduled chemotherapeutic drug administration, a 5-day course of granulocyte colony-stimulating factor (G-CSF) 5 μg/kg/d was given. RESULTS: The overall response rate was 42% for all 36 assessable patients (95% confidence interval, 26% to 59%), including two complete remissions (6%). Thirteen additional patients (36%) had stable disease, and only eight (22%) progressed. The median time to treatment failure was 7.5 months (range, 1 to 13.5+ months). After a median follow-up time of 14 months, 19 patients (53%) are still alive. Hematologic toxicity was commonly observed, although according to the ANC-adapted use of G-CSF (in 31 patients during 81 of 174 courses), it was generally mild: grade 3 and 4 granulocytopenia occurred in only five and two cases, respectively. The most frequent nonhematologic adverse reactions were nausea/emesis and diarrhea, which were rated severe in 17% and 19%, respectively. CONCLUSION: Our data suggest that the combination of irinotecan and oxaliplatin with or without G-CSF has substantial antitumor activity in patients with progressive fluoropyrimidine/leucovorin-pretreated colorectal cancer. Overall toxicity was modest, with gastrointestinal symptoms constituting the dose-limiting side effects. Further evaluation of this regimen seems warranted.
Automated Collection of Quality-of-Life Data: A Comparison of Paper and Computer Touch-Screen Questionnaires
Authors: Velikova G. , Wright E. P. , Smith A. B. , Cull A. , Gould A. , Forman D. , Perren T. , Stead M. , Brown J. , Selby P. J. 
Published: February 2017

PURPOSE: To evaluate alternative automated methods of collecting data on quality of life (QOL) in cancer patients. After initial evaluation of a range of technologies, we compared computer touch-screen questionnaires with paper questionnaires scanned by optical reading systems in terms of patients' acceptance, data quality, and reliability. PATIENTS AND METHODS: In a randomized cross-over trial, 149 cancer patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30, version 2.0 (EORTC QLQ-C30), and the Hospital Anxiety and Depression Scale (HADS) on paper and on a touch screen. In a further test-retest study, 81 patients completed the electronic version of the questionnaires twice, with a time interval of 3 hours between questionnaires. RESULTS: Fifty-two percent of the patients preferred the touch screen to paper; 24% had no preference. The quality of the data collected with the touch-screen system was good, with no missed responses. At the group level, the differences between scores obtained with the two modes of administration of the instruments were small, suggesting equivalence for most of the QOL scales, with the possible exception of the emotional, fatigue, and nausea/vomiting scales and the appetite item, where patients tended to give more positive responses on the touch screen. At the individual patient level, the agreement was good, with a kappa coefficient from 0.57 to 0.77 and percent global agreement from 61% to 97%. The electronic questionnaire had good test-retest reliability, with correlation coefficients between the two administrations from 0.78 to 0.95, kappa coefficients of agreement from 0.55 to 0.90, and percent global agreement from 56% to 100%. CONCLUSION: Computer touch-screen QOL questionnaires were well accepted by cancer patients, with good data quality and reliability.
Combined Modality Treatment for Osteosarcoma Occurring as a Second Malignant Disease
Authors: Bielack Stefan S. , Kempf-Bielack Beate , Heise Ulrich , Schwenzer Dorothea , Winkler Kurt 
Published: February 2017

PURPOSE: The prognosis of osteosarcoma occurring as a second malignant disease (OS-SMD) is thought to be poor. We attempted to evaluate whether this holds true when OS-SMD is treated with combined modality therapy as developed for primary osteosarcoma and if factors that influence survival might be identified. PATIENTS AND METHODS: All patients with OS-SMD registered at the Cooperative German-Austrian-Swiss Osteosarcoma Study Group (COSS) study center between 1980 and June 1996 were evaluated for patient- and treatment-related factors, local and systemic outcome, and survival. Therapy was to be given according to contemporary COSS protocols for primary extremity osteosarcoma, including surgery and multiagent chemotherapy. RESULTS: Thirty patients with OS-SMD were registered (median latency period, 9 years 2 months). The first malignancies had been retinoblastoma (10 patients), sarcoma (10 patients), lymphoma (five patients), carcinoma (four patients), and medulloblastoma (one patient). Treatment for these malignancies had included radiotherapy in 24 patients, surgery in 20, and chemotherapy in 14. Twelve osteosarcomas were located axially and 18 were located in an extremity; 17 were radiation-related. Twenty-seven patients presented with localized disease; three presented with primary metastases (two skip, one lung). All 30 patients received chemotherapy, 29 with multiple drugs. Twenty-eight patients underwent operation. At 7 years, actuarial overall survival, survival free from osteosarcoma progression, and survival free from progression of any cancer were 50%, 34%, and 30%, respectively. In 24 patients with local tumor control, the corresponding values were 63%, 46%, and 38%. All seven local failures occurred in patients with axial osteosarcomas who did not undergo operation with wide surgical margins. CONCLUSION: Provided that local tumor control is achieved, OS-SMD treated with combined modality therapy may have a prognosis that approaches that of otherwise comparable primary osteosarcoma.
Erythropoietin Addition to Granulocyte Colony-Stimulating Factor Abrogates Life-Threatening Neutropenia and Increases Peripheral-Blood Progenitor-Cell Mobilization After Epirubicin, Paclitaxel, and Cisplatin Combination Chemotherapy: Results of a Randomized Comparison
Authors: Pierelli Luca , Perillo Alessandro , Greggi Stefano , Salerno Giovanna , Panici Pierluigi Benedetti , Menichella Giacomo , Fattorossi Andrea , Leone Giuseppe , Mancuso Salvatore , Scambia Giovanni 
Published: February 2017

PURPOSE AND METHODS: The ability of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) treatment was compared in a randomized fashion with that of G-CSF treatment alone in promoting hematologic recovery and peripheral-blood progenitor-cell (PBPC) mobilization in previously untreated patients with advanced ovarian cancer who underwent their first course of epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy during a phase II study of intensive outpatient ETP chemotherapy followed by high-dose carboplatin, etoposide, and melphalan (CEM) late intensification with PBPC support. RESULTS: Comparative analysis of hematologic recovery of 50 randomized patients, after ETP chemotherapy, showed that life-threatening neutropenia occurred in 88% of the patients treated with G-CSF alone, whereas it occurred in only 4% of patients treated with G-CSF + EPO. Significantly different WBC and polymorphonuclear leukocyte (PMN) counts were observed in the two distinct arms on the day of WBC nadir (P < .0001 and P < .0001, respectively). Moreover, the addition of EPO to G-CSF increased PBPC mobilization and collection as compared with that in G-CSF–treated patients (P = .0009 and P = .0026, respectively), who required a significantly higher number of leukaphereses than G-CSF + EPO–treated patients (P = .0076) to obtain the planned minimum dose of PBPCs. Qualitative analysis by cloning assay of PBPCs collected in both arms revealed that G-CSF– and G-CSF + EPO–mobilized PBPCs have comparable in vitro functional properties. CONCLUSION: This randomized comparison revealed that EPO significantly increases most of the hematologic effect produced by G-CSF administration after chemotherapy. This biologic property of EPO translated in vivo into a global improvement of patients' hematologic status.
Combination of Oxaliplatin Plus Irinotecan in Patients With Gastrointestinal Tumors: Results of Two Independent Phase I Studies With Pharmacokinetics
Authors: Wasserman Ernesto , Cuvier Caroline , Lokiec François , Goldwasser François , Kalla Salima , Méry-Mignard Dominique , Ouldkaci Mahmoud , Besmaine Amine , Dupont-André Ghislaine , Mahjoubi Mondher , Marty Michel , Misset Jean-Louis , Cvitkovic Esteban 
Published: February 2017

PURPOSE: Two phase I studies of the oxaliplatin and irinotecan combination were performed in advanced gastrointestinal cancer patients to characterize the safety and pharmacokinetics of the regimen. PATIENTS AND METHODS: Patients with a performance status (PS) of ≤2 and normal hematologic, hepatic, and renal functions received oxaliplatin (2-hour intravenous infusion) followed 1 hour later by irinotecan administered over a 30-minute period, every 3 weeks. Dose levels that were explored ranged from 85 to 110 mg/m2 for oxaliplatin and 150 to 250 mg/m2 for irinotecan. Plasma pharmacokinetics of total and ultrafiltrable platinum, irinotecan, SN-38, and its glucuronide, SN-38G, were determined. RESULTS: Thirty-nine patients with gastrointestinal carcinomas (24 with colorectal cancer [CRC], four with pancreas cancer, four with gastric cancer, three with hepatocarcinoma, and four with other) received 216 treatment cycles. Median age was 54 years (range, 21 to 72 years); 95% had PS of 0 to 1; all but six had failed fluorouracil (5-FU) chemotherapy. The maximum-tolerated dose was oxaliplatin 110 mg/m2 plus irinotecan 200 mg/m2 in one study and oxaliplatin 110 mg/m2 plus irinotecan 250 mg/m2 in the other study. Grade 3 to 4 diarrhea and febrile neutropenia were dose-limiting toxicities; other toxicities included emesis and dose-cumulative neuropathy. Recommended dose for phase II studies is oxaliplatin 85 mg/m2 and irinotecan 200 mg/m2. At this dose (12 patients, 65 cycles), grade 3 and 4 toxicities per patient included the following: emesis in 42% of patients, neutropenia in 33% (febrile episodes in 17%), peripheral neuropathy in 25%, delayed diarrhea in 17%, and thrombocytopenia in 8%. Two patients with Gilbert's syndrome experienced severe irinotecan toxicity. No plasmatic pharmacokinetic interactions were detected. Seven partial responses were observed in 24 CRC patients. CONCLUSION: This combination is feasible, with activity in 5-FU–resistant CRC patients. Phase I studies that explore the every-2-weeks schedule, in addition to phase II studies of this schedule (as well as in combination with 5-FU) as second-line therapy of metastatic CRC, are ongoing.
Twenty Years of Phase III Trials for Patients With Extensive-Stage Small-Cell Lung Cancer: Perceptible Progress
Authors: Chute John P. , Chen Timothy , Feigal Ellen , Simon Richard , Johnson Bruce E. 
Published: February 2017

PURPOSE: All cooperative group studies performed in North America for patients with extensive-stage small-cell lung cancer (SCLC) were evaluated to determine the pattern of the clinical trials and the outcome of patients over the past 20 years. PATIENTS AND METHODS: Phase III trials for patients with extensive-stage SCLC were identified through a search of the National Cancer Institute Cancer Therapy Evaluation Program database from 1972 to 1993. Patients with extensive-stage SCLC treated during a similar time interval listed in the Surveillance, Epidemiology, and End Results (SEER) database were also examined. Trends were tested in the number of trials over time, the number and sex of patients entered onto the trials, and the survival time of patients treated over time. RESULTS: Twenty-one phase III trials for patients with extensive-stage SCLC were initiated between 1972 and1990. The median of the median survival times of patients treated on the control arms of the phase III trials initiated between 1972 and 1981 was 7.0 months; for those patients enrolled onto control arms between 1982 and 1990, the median survival time was 8.9 months (P = .001). Analysis of the SEER database of patients with extensive-stage SCLC over the same time period shows a similar 2-month prolongation in median survival time. CONCLUSION: Analysis of 21 phase III trials initiated in North America and the SEER database from 1972 to 1994 demonstrates that there has been a modest improvement in the survival time of patients with extensive-stage SCLC.
Phase I and Pharmacokinetic Study of a Daily Times 5 Short Intravenous Infusion Schedule of 9-Aminocamptothecin in a Colloidal Dispersion Formulation in Patients With Advanced Solid Tumors
Authors: Herben Virginie M.M. , van Gijn Roel , Schellens Jan H.M. , Schot Margaret , Lieverst Jan , Hillebrand Michel J.X. , Schoemaker Nadja E. , Porro Maria Grazia , Beijnen Jos H. , ten Bokkel Huinink Wim W. 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of 9-aminocamptothecin (9-AC) in a colloidal dispersion (CD) formulation administered as a 30-minute intravenous (IV) infusion over 5 consecutive days every 3 weeks. PATIENTS AND METHODS: Patients with solid tumors refractory to standard therapy were entered onto the study. The starting dose was 0.4 mg/m2/d. The MTD was assessed on the first cycle and was defined as the dose at which ≥ two of three patients or ≥ two of six patients experience DLT. Pharmacokinetic measurements were performed on days 1 and 5 of the first cycle and on day 4 of subsequent cycles using high-performance liquid chromatography. RESULTS: Thirty-one patients received 104+ treatment courses at seven dose levels. The DLT was hematologic. At a dose of 1.3 mg/m2/d, three of six patients experienced grade 3 thrombocytopenia. Grade 4 neutropenia that lasted less than 7 days was observed in four patients. At a dose of 1.1 mg/m2/d, four of nine patients had grade 4 neutropenia of brief duration, which was not dose limiting. Nonhematologic toxicities were relatively mild and included nausea/vomiting, diarrhea, obstipation, mucositis, fatigue, and alopecia. Maximal plasma concentrations and area under the concentration-time curve (AUC) increased linearly with dose, but interpatient variation was wide. Lactone concentrations exceeded 10 nmol/L, the threshold for activity in preclinical tumor models, at all dose levels. Sigmoidal Emax models could be fit to the relationship between AUC and the degree of hematologic toxicity. A partial response was observed in small-cell lung cancer. CONCLUSION: 9-AC CD administered as a 30-minute IV infusion daily times 5 every three weeks is safe and feasible. The recommended phase II dose is 1.1 mg/m2/d.
Nuclear Morphometry and Prognosis in Favorable Histology Wilms' Tumor: A Prospective Reevaluation
Authors: Breslow Norman E. , Partin Alan W. , Lee Benjamin R. , Guthrie Katherine A. , Beckwith J. Bruce , Green Daniel M. 
Published: February 2017

PURPOSE: This study was designed to evaluate the ability of a previously published nuclear morphometry discriminant function to predict disease-free survival in patients with Wilms' tumor. PATIENTS AND METHODS: We identified 218 patients with stage I-IV Wilms' tumor of favorable histology who were entered onto the National Wilms' Tumor Study (NWTS) between January 1, 1990 and April 15, 1994. The nuclear morphometry score was calculated for each patient as follows: MVf = (0.02 × AGE) + (1.17 × SNRF) + (90.6 × LEFD) − 94, with AGE denoting age at diagnosis in months, SNRF the skewness of the nuclear roundness factor, and LEFD the lowest value of nuclear ellipticity as measured by the feret diameter method. Relative risks of relapse were estimated for the total score and for each of its components. Sensitivity and specificity were determined for the criterion of “MVf is greater than −0.35” as a predictor of relapse. RESULTS: By contrast with previously published results, neither the SNRF nor the LEFD made any contribution to the prediction of disease-free survival. Sensitivity and specificity of the criterion of “MVf is greater than −0.35” were 71% and 56%, respectively. CONCLUSION: Re-evaluation of a published nuclear morphometry score showed that it did not predict disease-free survival in patients with Wilms' tumor. The earlier study very likely overestimated the predictive power of nuclear morphometry by using the same data set both to develop the score and to evaluate its properties. Because of the huge number of combinations of nuclear morphometry measurements that may enter into the multivariate discriminant function, use of appropriate statistical methods is essential to estimate accurately the sensitivity and specificity.
Phase I Trial of Multiple Cycles of High-Dose Chemotherapy Supported by Autologous Peripheral-Blood Stem Cells
Authors: Schilder Russell J. , Johnson Steven , Gallo James , Kindsfather Scott , Rogers Barbara , Bookman Michael A. , Millenson Michael M. , Boente Matthew , Rosenblum Norman , Litwin Samuel , Ozols Robert F. 
Published: February 2017

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin and paclitaxel with hematopoietic peripheral-blood stem cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with cyclophosphamide, etoposide, and granulocyte-macrophage colony-stimulating factor (GM-CSF). After one cycle of conventional-dose carboplatin and cyclophosphamide with GM-CSF, patients received multiple cycles of high-dose carboplatin (area under the concentration-time curve [AUC], 12 to 20) and paclitaxel (250 mg/m2) with PBSC and GM-CSF repeated every 28 days. RESULTS: Twenty-four of 28 patients were assessable for toxicity and clinical outcome. Dose-limiting toxicitieswere dehydration, diarrhea, and electrolyte imbalances. The maximum-tolerated dose of carboplatin was AUC 16 (equivalent to a median of 1,189 mg/m2). The relationship of target AUC to measured AUC was linear (r2 = .29; P = .0011). The overall response rate was 96%, with a complete clinical response rate of 67%. The median time to progression from the first PBSC reinfusion was 49.5 weeks (range, 8 to 156+ weeks). CONCLUSION: Multiple cycles of high-dose carboplatin (AUC 16) and paclitaxel (250 mg/m2) can be safely administered with GM-CSF and PBSC support. Although this regimen is safe, feasible, and active, the use of multiple cycles of high-dose chemotherapy as front-line treatment remains experimental and should only be used in the context of a clinical trial.