bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, Controlled, Dose-Range Study of Ro 25-8315 Given Before and After a High-Dose Combination Chemotherapy Regimen in Patients With Metastatic or Recurrent Breast Cancer Patients
Authors: Viens P. , Chabannon C. , Pouillard P. , Janvier M. , Brugger W. , Blay J. Y. , Oberling F. , Capdeville R. , Newman C. , Méresse V. , Xu Z. X. , Platzer E. , Van der Auwera P. , Maraninchi D. 
Published: February 2017

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 μg/kg, n = 9; 60 μg/kg, n = 9; 100 μg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 μg/kg/d; part II, 5 μg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 μg/kg. The peak of circulating CD34+ cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 × 109/L by day +15. In part II, high levels of circulating CD34+ cells (> 20 cells/μL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 × 109/L) was similar in the four groups. Ro 25-8315 100 μg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 × 109/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 μg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 μg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.
Salvage Chemotherapy for Patients With Advanced Pure Seminoma
Authors: Vuky Jacqueline , Tickoo Satish K. , Sheinfeld Joel , Bacik Jennifer , Amsterdam Alison , Mazumdar Madhu , Reuter Victor , Bajorin Dean F. , Bosl George J. , Motzer Robert J. 
Published: February 2017

PURPOSE: We describe the response to conventional or high-dose salvage chemotherapy in patients with advanced seminoma who experience disease progression after receiving first-line platinum-based treatment.PATIENTS AND METHODS: Twenty-seven patients with progressive, advanced, pure seminoma were treated with salvage chemotherapy. Fifteen patients were treated with conventional-dose cisplatin-and-ifosfamide combination chemotherapy. Twelve patients were treated with high-dose chemotherapy followed by autologous stem-cell rescue.RESULTS: Fifteen patients (56%) achieved a complete response (CR), nine achieved CR with a conventional-dose cisplatin and ifosfamide program, and six experienced CR after high-dose chemotherapy. Fourteen patients (52%) are alive and disease-free, with 13 (48%) continuously disease-free at a median follow-up of 72 months. Twelve (57%) of 21 patients whose pretreatment tumors were studied morphologically were found to have seminoma with atypia. Eight patients underwent resection after salvage chemotherapy; six with histologic findings of necrotic debris/fibrosis alone are alive and disease-free at last follow-up. Both patients with viable seminoma found at surgery died of disease.CONCLUSION: Most patients with advanced seminoma are cured with standard first-line programs of cisplatin and etoposide with or without bleomycin. A small minority of patients with pure seminoma have resistant tumors and require salvage chemotherapy. In this setting, approximately 50% of patients with recurrent pure seminoma achieve durable CR with conventional or high-dose salvage chemotherapy. Identification of biologic markers to predict clinical outcome and an enhanced understanding of the basic biologic features of seminoma may lead to improvements in the management of this disease.
Quality of Life in Long-Term Survivors of Testicular Cancer: A Population-Based Case-Control Study
Authors: Joly F. , Héron J. F. , Kalusinski L. , Bottet P. , Brune D. , Allouache N. , Macé-Lesec’h J. , Couëtte J. E. , Pény J. , Henry-Amar M. 
Published: February 2017

PURPOSE: To evaluate quality of life and social problems in long-term survivors of testicular cancer.PATIENTS AND METHODS: In 1998, 71 testicular cancer survivors (cases) identified from the Calvados General Tumor Registry were enrolled onto a case-control study. One hundred nineteen healthy control subjects (controls), matched by age and location of residence, were selected at random from electoral rolls. Three self-administered questionnaires were used: two health-related quality-of-life questionnaires (Short Form-36 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 core questionnaires) and one life situation questionnaire. Specific questions concerning sexuality were also added.RESULTS: With a mean follow-up of 11 years, health-related quality-of-life scores did not differ significantly between cases and controls, nor did general symptom scores. Psychosocial problems were reported equally by cases and controls. Cases reported more modification of sexual life (P = .04) with decreased sexual enjoyment (P < .01), decreased desire (P = .02), and infertility (P < .01). Cases did not report more divorce than controls; they reported fewer changes in relationships with friends (P = .03). Although a similar proportion of cases and controls were at work, cases expressed less ambitious professional plans (P = .002). Cases had greater difficulty in borrowing from banks (P < .001).CONCLUSION: French long-term survivors of testicular cancer do not express more impairment of health-related quality of life or familial or professional life in comparison with healthy men. They did have more sexual life problems and found difficulty in borrowing from banks. This information should be used by practitioners to help their patients cope with their disease and return to normal life.
Outcomes of Tamoxifen Chemoprevention for Breast Cancer in Very High-Risk Women: A Cost-Effectiveness Analysis
Authors: Hershman Dawn , Sundararajan Vijaya , Jacobson Judith S. , Heitjan Daniel F. , Neugut Alfred I. , Grann Victor R. 
Published: February 2017

PURPOSE: To estimate the effects on survival, quality-adjusted survival, and health care costs of using tamoxifen for primary prevention in subgroups of women at very high risk for breast cancer. PATIENTS AND METHODS: A decision analysis was performed using a hypothetical cohort of women that included subgroups with atypical hyperplasia, Gail risk greater than 5, lobular carcinoma-in-situ, or two or more first-degree relatives with breast cancer. Data sources were the Breast Cancer Prevention Trial, the Surveillance, Epidemiology, and End-Results program, time trade-off preference ratings, the Group Health Cooperative of Puget Sound, and the United States Health Care Financing Administration. RESULTS: Our model predicted that tamoxifen would prolong the average survival of cohort members initiating use at ages 35, 50, and 60 years by 70, 42, and 27 days, respectively. It would prolong survival even more for those in the higher-risk groups, especially those with atypical hyperplasia (202, 89, and 45 days). Tamoxifen use was also projected to extend quality-adjusted survival by 158, 80, and 50 days in the atypical hyperplasia group. For younger women in the highest risk groups, chemoprevention with tamoxifen was estimated to have cost savings or be cost-effective, both with and without quality adjustments. CONCLUSION: Chemoprevention with tamoxifen may be particularly beneficial to women with atypical hyperplasia, 5-year Gail model risk greater than 5%, lobular carcinoma-in-situ, or two or more first-degree relatives with breast cancer. The benefits may be greater if tamoxifen is initiated before age 50 years rather than after and if the breast cancer risk reduction conferred by tamoxifen lasts longer than 5 years. For women with a very high risk of invasive breast cancer, chemoprevention with tamoxifen seems to be cost-effective.
Granulocyte Colony-Stimulating Factor in Induction Treatment of Children With Non-Hodgkin’s Lymphoma: A Randomized Study of the French Society of Pediatric Oncology
Authors: Patte C. , Laplanche A. , Bertozzi A. I. , Baruchel A. , Frappaz D. , Schmitt C. , Mechinaud F. , Nelken B. , Boutard P. , Michon J. 
Published: February 2017

PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF; lenograstim) decreases the incidence of febrile neutropenia after induction courses in treatment of childhood non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Patients were randomized to receive (G-CSF+) or not receive (G-CSF−) prophylactic G-CSF, 5 μg/kg/d, from day 7 until an absolute neutrophil count ≥ 500/μL was sustained over 48 hours, after two consecutive induction courses of cyclophosphamide 1.5 or 3 g/m2, vincristine 2 mg/m2, prednisone 60 mg/m2/d × 5, doxorubicin 60 mg/m2, high-dose methotrexate 3 or 8 g/m2, and intrathecal injections (COPAD[M]) on protocols LMB89, LMT89, and HM91 of the French Society of Pediatric Oncology. RESULTS: One hundred forty-eight patients were assessable, 75 G-CSF+ and 73 G-CSF−. Although duration of neutropenia less than 500/μL was 3 days shorter in G-CSF+ patients (P = 10−4), incidence of febrile neutropenia (89% v 93% in the first course, 88% v 88% in the second course), durations of hospitalization and antimicrobial therapy, percentages of infections, mucositis, and transfusions were not significantly different. Although the percentage of G-CSF+ patients commencing the following course on day 21 was significantly higher (84% v 68% after the first and 57% v 38% after the second course; P < .05), the median delay between the two courses was only 1 day less in G-CSF+ patients (median delay after first COPAD(M), 19 v 20 days, P = .01; after second, 21 v 22 days, P = not significant). Remission and survival rates were similar in both arms. CONCLUSION: This study demonstrates that G-CSF did not decrease treatment-related morbidity, nor increase the dose-intensity in children undergoing COPAD(M) induction chemotherapy for NHL.
Intensive Salvage Therapy With High-Dose Chemotherapy for Patients With Advanced Hodgkin’s Disease in Relapse or Failure After Initial Chemotherapy: Results of the Groupe d’Études des Lymphomes de l’Adulte H89 Trial
Authors: Fermé Christophe , Mounier Nicolas , Diviné Marine , Brice Pauline , Stamatoullas Aspasia , Reman Oumedaly , Voillat Laurent , Jaubert Jérôme , Lederlin Pierre , Colin Philippe , Berger Françoise , Salles Gilles 
Published: February 2017

PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin’s disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P = .0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P = .0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival. CONCLUSION: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.
13-cis Retinoic Acid and Complete Androgen Blockade in Advanced Hormone-Naive Prostate Cancer Patients: Report of a Phase II Randomized Study
Authors: Ferrari Anna C. , Stone Nelson , Stock Richard , Bednar Myron , Esseesse Isaac , Singh Harvinder , Baldwin Yvonne , Mandeli John 
Published: February 2017

PURPOSE: 13 cis Retinoic acid (isotretinoin) is a retinoid with preclinical evidence of anti–prostate cancer activity. This phase II, cross-over, randomized study of advanced, predominantly androgen-dependent prostate cancer patients was designed to assess primarily the effect on prostate-specific antigen (PSA) decline and toxicity of adding isotretinoin to hormonal therapy and, secondarily, the potential antitumor activity of the combination. PATIENTS AND METHODS: Thirty-seven D0 to D2 patients were randomized soon after initiating luteinizing hormone–releasing hormone agonist with antiandrogen treatment to add (arm 1) or not (arm 2) isotretinoin from weeks 1 to 12. After cross-over on week 13, patients in arm 1 discontinued while patients in arm 2 added isotretinoin from weeks 14 to 25. Observation on hormonal therapy alone continued until week 49. RESULTS: Baseline and randomization median PSA for 30 assessable patients were, respectively, 34 and 18.2 ng/mL for arm 1 and 31 and 13.4 ng/mL for arm 2. Median PSA at week 13 was 0.5 ng/mL (range, < 0.05 to 136 ng/mL) for arm 1 and 0.7 ng/mL (range, < 0.05 to 4.4 ng/mL) for arm 2; at week 25, 0.1 ng/mL (range, < 0.05 to 121 ng/mL) and 0.4 ng/mL (range, < 0.05 to 3.1 ng/mL), respectively. At week 49, arm 1 had median PSA of 0.1 ng/mL (range, < 0.05 to 345 ng/mL) and arm 2, 0.3 ng/mL (range, < 0.05 to 8.8 ng/mL); seven of 15 and three of 15 patients, respectively, had undetectable PSA levels (P = .12). Frequent isotretinoin-related toxicity included grade 1 cheilitis (76%), skin dryness (43%), and elevated triglycerides (50%). CONCLUSION: Isotretinoin does not impair PSA decline or add significant toxicity to hormonal therapy. An adequately powered, randomized study would be required to determine whether the combination is superior to standard hormonal treatment.
Lymphatic Mapping and Sentinel Node Identification in Patients With Cervix Cancer Undergoing Radical Hysterectomy and Pelvic Lymphadenectomy
Authors: Levenback Charles , Coleman Robert L. , Burke Thomas W. , Lin W. Michael , Erdman William , Deavers Michael , Delpassand Ebrahim S. 
Published: February 2017

PURPOSE: The purpose of this study was to determine the feasibility of sentinel node identification in patients with invasive cervix cancer undergoing radical hysterectomy and pelvic lymphadenectomy using preoperative and intraoperative lymphatic mapping. PATIENTS AND METHODS: Thirty-nine patients at two institutions were enrolled onto this institutional review board–approved study. All underwent preoperative lymphoscintigraphy and intraoperative lymphatic mapping with blue dye and a handheld gamma probe. Radical hysterectomy was aborted in four patients because metastatic disease was discovered on frozen section analysis of the sentinel node. RESULTS: Preoperative lymphoscintigraphy revealed at least one sentinel node in 33 patients (85%), including 21 (55%) with bilateral sentinel nodes. All 39 patients had at least one sentinel node identified intraoperatively. Eighty percent of sentinel nodes were in three pelvic locations: iliac, obturator, and parametrial (in descending order of frequency). The remaining sentinel nodes were in the common iliac and para-aortic nodal basins. A total of 132 nodes were identified clinically as sentinel nodes; 65 (49%) were both blue and hot, 35 (27%) were blue only, and 32 (24%) were hot only. Eight patients (21%) had metastatic disease. In five of these patients, sentinel nodes were the only positive lymph nodes. One patient had false-negative sentinel nodes. She had four microscopically positive parametrial nodes that were resected in continuity with the uterus. The sensitivity of the sentinel node was 87.5% and the negative predictive value was 97%. CONCLUSION: Preoperative lymphoscintigraphy and intraoperative lymphatic mapping were highly successful at identifying sentinel nodes in patients undergoing radical hysterectomy.
Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer
Authors: Vogel Charles L. , Cobleigh Melody A. , Tripathy Debu , Gutheil John C. , Harris Lyndsay N. , Fehrenbacher Louis , Slamon Dennis J. , Murphy Maureen , Novotny William F. , Burchmore Michael , Shak Steven , Stewart Stanford J. , Press Michael 
Published: February 2017

PURPOSE: To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS: One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. RESULTS: The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. CONCLUSION: Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.
Influence of Letrozole and Anastrozole on Total Body Aromatization and Plasma Estrogen Levels in Postmenopausal Breast Cancer Patients Evaluated in a Randomized, Cross-Over Study
Authors: Geisler Jürgen , Haynes Ben , Anker Gun , Dowsett Mitch , Lønning Per Eystein 
Published: February 2017

PURPOSE: To compare the effects of the two novel, potent, nonsteroidal aromatase inhibitors anastrozole and letrozole on total-body aromatization and plasma estrogen levels. PATIENTS AND METHODS: Twelve postmenopausal women with estrogen receptor–positive, metastatic breast cancer were treated with anastrozole 1 mg orally (PO) and letrozole 2.5 mg PO once daily, each given for a time interval of 6 weeks in a randomized sequence. Total-body aromatization was determined before treatment and at the end of each treatment period using a dual-label isotopic technique involving isolation of the metabolites with high-performance liquid chromatography. Plasma levels of estrone (E1), estradiol (E2), and estrone sulfate (E1S) were determined in samples obtained before each injection using highly sensitive radioimmunoassays. RESULTS: Pretreatment aromatase levels ranged from 1.68% to 4.27%. On-treatment levels of aromatase were detectable in 11 of 12 patients during treatment with anastrozole (mean percentage inhibition in the whole group, 97.3%) but in none of the 12 patients during treatment with letrozole (> 99.1% suppression in all patients; Wilcoxon, P = .0022, comparing the two drug regimens). Treatment with anastrozole suppressed plasma levels of E1, E2, and E1S by a mean of 81.0%, 84.9%, and 93.5%, respectrively, whereas treatment with letrozole caused a corresponding decrease of 84.3%, 87.8% and 98.0%, respectively. The suppression of E1 and E1S was found to be significantly better during treatment with letrozole compared with anastrozole (P = .019 and .0037, respectively). CONCLUSION: This study revealed letrozole (2.5 mg once daily) to be a more potent suppressor of total-body aromatization and plasma estrogen levels compared with anastrozole (1 mg once daily) in postmenopausal women with metastatic breast cancer.
Acute Side Effects and Complications After Short-Term Preoperative Radiotherapy Combined With Total Mesorectal Excision in Primary Rectal Cancer: Report of a Multicenter Randomized Trial
Authors: Marijnen C. A.M. , Kapiteijn E. , van de Velde C. J.H. , Martijn H. , Steup W. H. , Wiggers T. , Kranenbarg E. Klein , Leer J. W.H. ,   the Cooperative Investigators of the Dutch Colorectal Cancer Group
Published: February 2017

PURPOSE: Total mesorectal excision (TME) surgery in the treatment of rectal cancer has been shown to result in a reduction in the number of local recurrences in retrospective studies. Reports on improved local control after preoperative, hypofractionated radiotherapy (RT) have led to the introduction of a prospective randomized multicenter trial, in which the effect of TME surgery with or without preoperative RT were evaluated. Any benefit in regard to a reduced local recurrence rate and possible improved survival must be weighed against potential adverse effects in both the short-term and the long-term. The present study was undertaken to assess the acute side effects of short-term, preoperative RT in rectal cancer patients and to study the influence of five doses of 5 Gy on surgical parameters, postoperative morbidity and mortality in patients randomized in the Dutch TME trial. PATIENTS AND METHODS: We analyzed 1,530 Dutch patients entered onto a prospective randomized trial, comparing preoperative RT with five doses of 5 Gy followed by TME surgery with TME surgery alone, of which 1,414 patients were assessable. Toxicity from RT, surgery characteristics, and postoperative complications and mortality were compared. RESULTS: Toxicity during RT hardly occurred. Irradiated patients had 100 mL more blood loss during the operation (P < .001) and showed more perineal complications (P = .008) in cases of abdominoperineal resection. The total number of complications was slightly increased in the irradiated group (P = .008). No difference was observed in postoperative mortality (4.0% v 3.3%) or in the number of reinterventions. CONCLUSION: Preoperative hypofractionated RT is a safe procedure in patients treated with TME surgery, despite a slight increase in complications when compared with TME surgery only.