bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localized Childhood Hodgkin’s Disease: Response-Adapted Chemotherapy With Etoposide, Bleomycin, Vinblastine, and Prednisone Before Low-Dose Radiation Therapy—Results of the French Society of Pediatric Oncology Study MDH90
Authors: Landman-Parker J. , Pacquement H. , Leblanc T. , Habrand J.L. , Terrier-Lacombe M.J. , Bertrand Y. , Perel Y. , Robert A. , Coze C. , Thuret I. , Donadieu J. , Schaison G. , Leverger G. , Lemerle J. , Oberlin O. 
Published: February 2017

PURPOSE: The French Society of Pediatric Oncology MDH82 study demonstrated the effectiveness of 20 Gy irradiation of involved fields after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone/ABVD chemotherapy in children with localized Hodgkin’s disease (HD). The response to primary chemotherapy was the only predictor of survival. To reduce long-term treatment complications without compromising efficacy, the MDH90 study was based on a new chemotherapy regimen devoid of both alkylating agents and anthracycline, followed by 20 Gy of radiotherapy (RT) for good responders. PATIENTS AND METHODS: From January 1990 to July 1996, 202 children were enrolled from 30 institutions. Good responders to four cycles of vinblastine, bleomycin, etoposide (VP16), and prednisone (VBVP) were given 20 Gy of RT and no further therapy. Poor responders were given vincristine, procarbazine, prednisone, and doxorubicin. After a second evaluation, good responders were given 20 Gy of RT, and poor responders were given 40 Gy of RT. RESULTS: One hundred seventy-one patients (85%) were good responders to VBVP, 27 (15%) were poor responders, and four did not respond. With a median follow-up of 74 months (range, 25 to 117 months), the 5-year overall survival rate (mean ± SD) is 97.5% ± 2.1%, and the event-free survival rate (mean ± SD) is 91.1% ± 1.8%. Significant predictors of worse event-free survival in multivariate analysis were hemoglobin < 10.5 g/L, “b” biologic class, and nodular sclerosis. CONCLUSION: These results suggest that most children with clinical stage I and II HD can be treated with chemotherapy devoid of alkylating agents and anthracycline, followed by low-dose RT.
Six Months of Maintenance Chemotherapy After Intensified Treatment for Acute Lymphoblastic Leukemia of Childhood
Authors: Toyoda Yasunori , Manabe Atsushi , Tsuchida Masahiro , Hanada Ryohji , Ikuta Koichiro , Okimoto Yuri , Ohara Akira , Ohkawa Yohji , Mori Taijiroh , Ishimoto Kohichi , Sato Takeyuki , Kaneko Takashi , Maeda Miho , Koike Ken-ichi , Shitara Toshiji , Hoshi Yasutaka , Hosoya Ryohta , Tsunematsu Yukiko , Bessho Fumio , Nakazawa Shinpei , Saito Tomohiro ,   for the Acute Lymphoblastic Leukemia Committee of the Tokyo Children’s Cancer Study Group
Published: February 2017

PURPOSE: We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy. PATIENTS AND METHODS: Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92–13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis. RESULTS: The mean (± SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% ± 3.4% and 81.5% ± 2.2%, respectively, at 5.5 years after diagnosis. EFS rates by risk category were similar (60.2% ± 6.0% for standard risk, 57.7% ± 5.6% for high risk, and 62.5% ± 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% ± 2.7%, 80.0% ± 4.1%, and 72.1% ± 4.5%, respectively, P < .0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% ± 7.9% (standard risk), 42.6% ± 8.1% (high risk), and 9.6% ± 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important. CONCLUSION: Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.
Use of Recombinant Human Granulocyte Colony-Stimulating Factor to Increase Chemotherapy Dose-Intensity: A Randomized Trial in Very High-Risk Childhood Acute Lymphoblastic Leukemia
Authors: Michel G. , Landman-Parker J. , Auclerc M.F. , Mathey C. , Leblanc T. , Legall E. , Bordigoni P. , Lamagnere J.P. , Demeocq F. , Perel Y. , Auvrignon A. , Berthou C. , Bauduer F. , Pautard B. , Schneider P. , Schaison G. , Leverger G. , Baruchel A. 
Published: February 2017

PURPOSE: To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 × 109/L and platelet count was > 100 × 109/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval). RESULTS: CDI was significantly increased in the G-CSF group compared with the non–G-CSF group (mean ± 95% confidence interval, 105 ± 5% v 91 ± 4%; P < .001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups. CONCLUSION: G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.
Adjuvant Therapy of Stage III and IV Malignant Melanoma Using Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Spitler Lynn E. , Grossbard Michael L. , Ernstoff Marc S. , Silver Gary , Jacobs Mark , Hayes F. Ann , Soong Seng Jaw 
Published: February 2017

PURPOSE: To evaluate granulocyte-macrophage colony-stimulating factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk of recurrence.PATIENTS AND METHODS: Forty-eight assessable patients with stage III or IV melanoma were treated in a phase II trial with long-term, chronic, intermittent GM-CSF after surgical resection of disease. Patients with stage III disease were required to have more than four positive nodes or a more than 3-cm mass. All patients were rendered clinically disease-free by surgery before enrollment. The GM-CSF was administered subcutaneously in 28-day cycles, such that a dose of 125 μg/m2was delivered daily for 14 days followed by 14 days of rest. Treatment cycles continued for 1 year or until disease recurrence. Patients were evaluated for toxicity and disease-free and overall survival.RESULTS: Overall and disease-free survival were significantly prolonged in patients who received GM-CSF compared with matched historical controls. The median survival duration was 37.5 months in the study patients versus 12.2 months in the matched controls (P < .001). GM-CSF was well tolerated; only one subject discontinued drug due to an adverse event (grade 2 injection site reaction).CONCLUSION: GM-CSF may provide an antitumor effect that prolongs survival and disease-free survival in patients with stage III and IV melanoma who are clinically disease-free. These results support institution of a prospective, randomized clinical trial to definitively determine the value of surgical adjuvant therapy with GM-CSF in such patients.
Phase I Trial of Recombinant Immunotoxin Anti-Tac(Fv)-PE38 (LMB-2) in Patients With Hematologic Malignancies
Authors: Kreitman Robert J. , Wilson Wyndham H. , White Jeffrey D. , Stetler-Stevenson Maryalice , Jaffe Elaine S. , Giardina Steven , Waldmann Thomas A. , Pastan Ira 
Published: February 2017

PURPOSE: To evaluate the toxicity, pharmacokinetics, immunogenicity, and antitumor activity of anti-Tac(Fv)-PE38 (LMB-2), an anti-CD25 recombinant immunotoxin that contains an antibody Fv fragment fused to truncated Pseudomonas exotoxin.PATIENTS AND METHODS: Patients with CD25+hematologic malignancies for whom standard and salvage therapies failed were treated with LMB-2 at dose levels that ranged from 2 to 63 μg/kg administered intravenously over 30 minutes on alternate days for three doses (QOD × 3).RESULTS: LMB-2 was administered to 35 patients for a total of 59 cycles. Dose-limiting toxicity at the 63 μg/kg level was reversible and included transaminase elevations in one patient and diarrhea and cardiomyopathy in another. LMB-2 was well tolerated in nine patients at the maximum-tolerated dose (40 μg/kg QOD × 3); toxicity was transient and most commonly included transaminase elevations (eight patients) and fever (seven patients). Only six of 35 patients developed significant neutralizing antibodies after the first cycle. The median half-life was 4 hours. One hairy cell leukemia (HCL) patient achieved a complete remission, which is ongoing at 20 months. Seven partial responses were observed in cutaneous T-cell lymphoma (one patient), HCL (three patients), chronic lymphocytic leukemia (one patient), Hodgkin’s disease (one patient), and adult T-cell leukemia (one patient). Responding patients had 2 to 5 log reductions of circulating malignant cells, improvement in skin lesions, and regression of lymphomatous masses and splenomegaly. All four patients with HCL responded to treatment.CONCLUSION: LMB-2 has clinical activity in CD25+hematologic malignancies and is relatively nonimmunogenic. It is the first recombinant immunotoxin to induce major responses in cancer. LMB-2 and similar agents that target other cancer antigens merit further clinical development.
Phase I and Pharmacologic Study of Sequences of Gemcitabine and the Multitargeted Antifolate Agent in Patients With Advanced Solid Tumors
Authors: Adjei Alex A. , Erlichman Charles , Sloan Jeff A. , Reid Joel M. , Pitot Henry C. , Goldberg Richard M. , Peethambaram Prema , Atherton Pamela , Hanson Lorelei J. , Alberts Steven R. , Jett James 
Published: February 2017

PURPOSE: Multitargeted antifolate (MTA) is an investigational agent that, like gemcitabine, exhibits broad activity in solid tumors. A phase I trial of MTA and gemcitabine was undertaken, based on the demonstration of preclinical cytotoxic synergy. PATIENTS AND METHODS: Thirty-five patients (group I) received 164 courses (median, four; range, one to 14 courses) of treatment of gemcitabine at doses of 1,000 and 1,250 mg/m2 on days 1 and 8 and MTA at doses of 200, 300, 400, 500, and 600 mg/m2, given 90 minutes after gemcitabine on day 1. Courses were repeated every 3 weeks. Because the day 8 dose of gemcitabine was reduced or omitted in 57% of courses due to neutropenia, 21 patients (group II) were treated on an alternate schedule, with MTA administered on day 8 rather than day 1. This group received 85 treatment courses (median, four; range, one to 10 courses). RESULTS: The most common and dose-limiting toxicity was neutropenia. Other toxicities included nausea, fatigue, rash, and elevated hepatic transaminases. The maximum-tolerated dose was gemcitabine/MTA 1,000/500 mg/m2 for group I and 1,250/500 mg/m2 for group II. Thirteen objective responses were documented (colorectal cancer, n = 3; non–small-cell lung cancer, n = 3; cholangiocarcinoma, n = 2; ovarian carcinoma, n = 2; mesothelioma, n = 1; breast cancer, n = 1; and adenocarcinoma of unknown primary site, n = 1). Gemcitabine had no effect on the disposition of MTA. CONCLUSION: The gemcitabine/MTA combination is broadly active and warrants further evaluation. The sequence of gemcitabine administered on days 1 and 8 with MTA administered on day 8 is better tolerated and is recommended for further study at doses of gemcitabine/MTA 1,250/500 mg/m2.
Growth Factor Usage Patterns and Outcomes in the Community Setting: Collection Through a Practice-Based Computerized Clinical Information System
Authors: Swanson Grant , Bergstrom Kim , Stump Eva , Miyahara Tammi , Herfindal E.T. 
Published: February 2017

PURPOSE: Although use of colony-stimulating factor (CSF) is widespread and guidelines for use have been disseminated, actual practice patterns of medical oncologists are unknown. The purpose of this study was to collect these data using an office-based computerized clinical information system. PATIENTS AND METHODS: Data were collected on patients at 10 community-based oncology practices. Information regarding CSF use was captured at the time of prescribing through a computerized clinical support tool and stored in a data warehouse, and an analysis was carried out retrospectively. RESULTS: A total of 6,813 cancer regimens administered to 5,034 patients were evaluated for growth factor use. Overall, CSFs were used in 14% of regimens, with breast, lymphoma, lung, and ovarian being the most common cancers for which CSFs were used. In 49.4% of regimens, CSF was initiated during cycle 1, with an average duration of 1 week, and was used in two or three cycles per regimen. Afebrile neutropenia is rarely followed by CSF initiation. Granulocyte colony-stimulating factor (G-CSF) is associated with fewer dose adjustments, delays, and hospitalizations when compared with granulocyte-macrophage colony stimulating factor (GM-CSF). There is wide variation among oncologists in CSF use, and several substantial differences were noted between the prescribing behavior of American Society of Clinical Oncology (ASCO) survey–reported oncologists and actual clinical practice, as captured by the computerized clinical information system. CONCLUSION: Computerized clinical information systems can collect detailed information regarding practice patterns of medical oncologists. ASCO physician practice survey data do not accurately reflect actual practice patterns and must be interpreted with caution. Substantial deviations from ASCO growth factor guidelines remain, and oncologists’ use of CSFs demonstrates wide variation. There may be important clinical differences between G-CSF and GM-CSF, but definitive phase III trials are needed for confirmation.
Mitoxantrone, Etoposide, and Cyclosporine Therapy in Pediatric Patients With Recurrent or Refractory Acute Myeloid Leukemia
Authors: Dahl Gary V. , Lacayo Norman J. , Brophy Nathalie , Dunussi-Joannopoulos Kyriaki , Weinstein Howard J. , Chang Myron , Sikic Branimir I. , Arceci Robert J. 
Published: February 2017

PURPOSE: To determine the remission rate and toxicity of mitoxantrone, etoposide, and cyclosporine (MEC) therapy, multidrug resistance-1 (MDR1) status, and steady-state cyclosporine (CSA) levels in children with relapsed and/or refractory acute myeloid leukemia. PATIENTS AND METHODS: MEC therapy consisted of mitoxantrone 6 mg/m2/d for 5 days, etoposide 60 mg/m2/d for 5 days, and CSA 10 mg/kg for 2 hours followed by 30 mg/kg/d as a continuous infusion for 98 hours. Because of pharmacokinetic interactions, drug doses were decreased to 60% of those found to be effective without coadministration of CSA. MDR1 expression was evaluated by reverse transcriptase polymerase chain reaction, flow cytometry, and the ability of CSA at 2.5 μmol/L to increase intracellular accumulation of 3H-daunomycin in blasts from bone marrow specimens. RESULTS: The remission rate was 35% (n = 23 of 66). Overall, 35% of patients (n = 23) achieved complete remission (CR), 12% of patients (n = 8) achieved partial remission, and 9% of patients (n = 6) died of infection. Exposure to CSA levels of greater than 2,400 ng/mL was achieved in 95% of patients (n = 56 of 59). Toxicities included infection, cardiotoxicity, myelosuppression, stomatitis, and reversible increases in serum creatinine and bilirubin. In most who had relapsed while receiving therapy or whose induction therapy had failed, response was not significantly different for MDR1-positive and MDR1-negative patients. CONCLUSION: Serum levels of CSA capable of reversing multidrug resistance are achievable in children with acceptable toxicity. The CR rate of 35% achieved in this study is comparable to previously reported results using standard doses of mitoxantrone and etoposide. The use of CSA may have improved the response rate for the MDR1-positive patients so that it was not different from that for the MDR1-negative patients.
Phase I Trials in Pediatric Oncology: Perceptions of Pediatricians From the United Kingdom Children’s Cancer Study Group and the Pediatric Oncology Group
Authors: Estlin E.J. , Cotterill S. , Pratt C.B. , Pearson A.D. J. , Bernstein M. 
Published: February 2017

PURPOSE: To identify areas of concern regarding the conduct of phase I trials, the perceived expectations and motivations of the parents of children entered, the expectations of toxicity and benefit, and the ethical concerns of pediatric hematologists and oncologists in the United Kingdom and North America. METHODS: A survey instrument consisting of 19 open- and closed-ended questions was sent to United Kingdom Children’s Cancer Study Group (UKCCSG)– and Pediatric Oncology Group (POG)–affiliated pediatricians. RESULTS: Fifty-three UKCCSG- and 78 POG-affiliated pediatricians responded. Thirty-two UKCCSG and 51 POG respondents had previously entered at least one child into a phase I study. Overall, respondents believed that parents entered their children for medical benefit, altruism, and hope of cure. Although many respondents believed that children could benefit from medical improvement, feelings of altruism, and maintenance of hope, the chance of cure or complete remission was thought to be small. Similarly, parents were thought to potentially benefit through altruism and maintenance of hope. Whereas 83% of UKCCSG respondents indicated that phase I trials were associated with ethical difficulties, this was a concern for 48% of POG respondents. The main ethical concerns of respondents were risk of toxicity, consent of the child, unrealistic hope, and coercion. CONCLUSION: The respondents in this survey expressed mainly ethical concerns regarding the conduct of phase I trials and had realistic expectations of the potential for toxicity and benefit for those children who participate in these studies.
Prognostic Value of p53 for Local Failure in Mastectomy-Treated Breast Cancer Patients
Authors: Zellars R.C. , Hilsenbeck S.G. , Clark G.M. , Allred D.C. , Herman T.S. , Chamness G.C. , Elledge R.M. 
Published: February 2017

PURPOSE: The loss of p53 function is a recognized adverse prognostic factor in invasive breast cancer. Several studies have shown a relationship between the nuclear accumulation of p53 protein (a surrogate marker of p53 inactivation) and poor disease-free and overall survival. In general, however, these studies did not report the prognostic value of p53 for local failure, which we have therefore assessed retrospectively here. MATERIALS AND METHODS: Accumulation of p53 protein was evaluated by immunohistochemistry in 1,530 mastectomy-treated breast cancer patients (259 radiation therapy [RT]– and 1,271 mastectomy only [No RT]–treated patients). Statistical comparisons were made between p53 protein accumulation, estrogen/progesterone receptors, nodal status, tumor size, and local failure rate (LFR). Local failure was defined as tumor recurrence involving the chest wall and/or the ipsilateral supraclavicular/axillary lymph nodes. The median follow-up period was 62 months. RESULTS: In the No RT group, the LFR was 9.1% and 16.5% in p53-negative and p53-positive patients, respectively (P < .001). Multivariate analysis revealed that p53 protein accumulation was significantly associated with an increased risk of local relapse (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2 to 2.4). Nodal status and tumor size were also significant factors. In the RT group, the LFR was 9.3% and 21.5% in p53-negative and p53-positive patients, respectively (P = .009). Multivariate analysis revealed that p53 protein accumulation was significantly associated with an increased risk of local relapse (RR, 2.5; 95% CI, 1.1 to 5.7), as was nodal status. CONCLUSION: Nuclear accumulation of p53 protein is independently associated with a significantly increased local failure rate in breast cancer patients treated with mastectomy, with or without radiation.
Profile of Men Randomized to the Prostate Cancer Prevention Trial: Baseline Health-Related Quality of Life, Urinary and Sexual Functioning, and Health Behaviors
Authors: Moinpour Carol M. , Lovato Laura C. , Thompson Ian M. , Ware John E. , Ganz Patricia A. , Patrick Donald L. , Shumaker Sally A. , Donaldson Gary W. , Ryan Anne , Coltman Charles A. 
Published: February 2017

PURPOSE: To describe men who agreed to be randomized to the Prostate Cancer Prevention Trial (PCPT), a 7-year, double-blind placebo-controlled study of the efficacy of finasteride in preventing prostate cancer. METHODS: Comprehensive health-related quality-of-life data are presented for 18,882 randomized PCPT participants. RESULTS: PCPT participants are highly educated, middle to upper income, and primarily white (92%). Participants reported healthy lifestyles. The mean American Urological Association Symptom Index score was well below the maximum entry score of less than 19; existing urinary symptoms were generally not bothersome. The scores for two sexual functioning scales could range from 0 to 100, with higher scores reflecting worse sexual functioning. The mean score for the Sexual Problem Scale was 19.2 out of 100, and the mean Sexual Activities Scale was 44.1 out of 100. Scores for seven of the eight Medical Outcomes Study 36-item Short-Form Health Survey scales (higher scores are better) were 10 to 20 points higher than those reported by a general population sample and differed minimally by race but not by age. Previously reported associations between sexual dysfunction and hypertension, diabetes, and depression were also observed. Men who never smoked reported less sexual dysfunction than did those who either had quit or still smoked. CONCLUSION: Individuals who are likely to enroll in primary prevention trials have a high socioeconomic status, healthy lifestyle behaviors, and better health than the general population. These data help oncologists design chemoprevention trials with respect to the selection of health-related quality-of-life assessments and recruitment strategies.