bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of Cisplatin and Paclitaxel in Advanced Carcinoma of the Urothelium: An Eastern Cooperative Oncology Group Study
Authors: Dreicer Robert , Manola Judith , Roth Bruce J. , Cohen Michael B. , Hatfield Alan K. , Wilding George 
Published: February 2017

PURPOSE: Cisplatin and paclitaxel are active agents in advanced urothelial cancer. A phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multi-institutional setting. PATIENTS AND METHODS: Fifty-two patients with advanced urothelial carcinoma were treated on one day with paclitaxel 175 mg/m2 over 3 hours followed by cisplatin 75 mg/m2, both intravenously, every 21 days. Cycles were repeated every 21 days until progression or a maximum of six cycles. RESULTS: Twenty-six patients obtained an objective response, for an overall response rate of 50% (95% confidence interval, 36% to 64%). Four patients achieved complete clinical responses. The median overall survival time for the group was 10.6 months. Toxicity was moderate, with granulocytopenia and neurotoxicity being the most common side effects noted. CONCLUSION: The combination of cisplatin and paclitaxel is active in advanced urothelial cancer. Responses in visceral, nodal, and soft tissues sites were observed. Granulocytopenia without fever and grade 2/3 neurotoxicity were common. The confidence interval of the overall response rate in this study overlaps most of the other reported regimens. The optimal therapy for advanced urothelial cancer remains undefined.
Evaluation of Soy Phytoestrogens for the Treatment of Hot Flashes in Breast Cancer Survivors: A North Central Cancer Treatment Group Trial
Authors: Quella Susan K. , Loprinzi Charles L. , Barton Debra L. , Knost James A. , Sloan Jeff A. , LaVasseur Beth I. , Swan Debra , Krupp Kenneth R. , Miller Kathy D. , Novotny Paul J. 
Published: February 2017

PURPOSE: Hot flashes represent a significant clinical problem for some breast cancer survivors. Safe, effective treatment is needed for this prominent clinical problem. Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem, there are continued safety concerns regarding the use of hormonal therapies in these women. Based on anecdotal information, we hypothesized that soy-derived phytoestrogens, weak estrogen-like substances in the soybean that demonstrate estrogen agonist and/or antagonist effects when they bind to estrogen receptors, could alleviate hot flashes. This current trial was designed to investigate this hypothesis. PATIENTS AND METHODS: This double-blind clinical trial involved breast cancer survivors with substantial hot flashes. After randomization, patients underwent a 1-week baseline period with no therapy. This was followed by 4 weeks of either soy tablets or placebo. The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks. Patients completed a daily questionnaire documenting hot flash frequency, intensity, and perceived side effects. RESULTS: Of the 177 women who were randomized and started the study substance, 155 (88%) provided useable data over the first 5 weeks; 149 provided usable data over the entire 9 weeks. There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo. At study completion, patients preferred the soy product 33% of the time, the placebo 37% of the time, and neither substance 31% of the time. No toxicity was observed. CONCLUSION: The soy product did not alleviate hot flashes in breast cancer survivors.
Long-Term Prognosis After Resection of Hepatocellular Carcinoma Associated With Hepatitis B–Related Cirrhosis
Authors: Poon Ronnie Tung-Ping , Fan Sheung-Tat , Lo Chung-Mau , Liu Chi-Leung , Ng Irene Oi-Lin , Wong John 
Published: February 2017

PURPOSE: The optimum management of hepatocellular carcinoma (HCC) associated with cirrhosis has not yet been clarified. Very few data are available in the literature regarding the prognosis after resection of HCC associated with hepatitis B virus (HBV)–related cirrhosis. This study evaluated the long-term results and prognostic factors after resection of HCC complicating HBV-related cirrhosis. PATIENTS AND METHODS: One hundred forty-six patients with HBV-related Child’s A or B cirrhosis who had undergone resection of HCC over a 10-year period were prospectively studied for long-term results. They were compared with 155 noncirrhotic patients with HBV-related HCC resected in the same period. RESULTS: The overall survival results of cirrhotic patients after resection of HCC were comparable to those of noncirrhotic patients (5-year survival, 44.3% v 45.6%, respectively; P = .216), but the former group had significantly smaller tumors. Stratified according to tumor size, the survival results were similar between cirrhotic and noncirrhotic patients with tumors ≤ 5 cm (5-year survival, 60.7% v 61.7%, respectively; P = .327) but were worse in cirrhotic compared with noncirrhotic patients with tumors greater than 5 cm (5-year survival, 27.8% v 39.5%, respectively; P = .034). Stage by stage, there were no significant differences in survival results between cirrhotic and noncirrhotic patients. Preoperative serum AST level greater than 100 IU/L (P = .004), perioperative transfusion (P = .015), and venous invasion (P < .001) were independent adverse prognostic factors. CONCLUSION: The prognosis after resection of HCCs less than 5 cm in patients with compensated HBV-related cirrhosis was comparable to that of noncirrhotic patients, which suggests that surgical resection may be considered a first-line treatment for these patients. Patients with underlying active hepatitis as indicated by a high preoperative transaminase level are less favorable candidates for resection. Further studies are needed to define the relative roles of resection and transplantation for HCC associated with hepatitis B cirrhosis.
Pharmacokinetics of Nelarabine and 9-Beta-d-Arabinofuranosyl Guanine in Pediatric and Adult Patients During a Phase I Study of Nelarabine for the Treatment of Refractory Hematologic Malignancies
Authors: Kisor David F. , Plunkett William , Kurtzberg Joanne , Mitchell Beverly , Hodge Jeffrey P. , Ernst Timothy , Keating Michael J. , Gandhi Varsha 
Published: February 2017

PURPOSE: To characterize the pharmacokinetics of nelarabine (506U78), the water-soluble prodrug of 9-beta-d-arabinofuranosyl guanine (ara-G), and ara-G in pediatric and adult patients with refractory hematologic malignancies. Ara-G is phosphorylated within leukemic cells to form ara-G triphosphate (ara-GTP), which acts to terminate DNA chain elongation, resulting in cell death. PATIENTS AND METHODS: The pharmacokinetics of nelarabine and/or ara-G were evaluated in 71 patients (25 pediatric and 46 adult patients) on the first day of therapy. Blood was collected at specified times for the determination of plasma nelarabine and ara-G concentrations. RESULTS: There were no statistically significant differences in the pharmacokinetics of nelarabine between any of the groups of patients. The harmonic mean half-life (t1/2) of nelarabine in pediatric and adult patients was 14.1 minutes and 16.5 minutes, respectively. The maximum concentrations (Cmax) of ara-G occurred at or near the end of the nelarabine infusion. The Cmax of ara-G ranged from 11.6 μmol/L to 308.7 μmol/L at nelarabine doses of 5 to 75 mg/kg and was linearly related to the nelarabine dose. No statistically significant differences were noted for the pharmacokinetic parameter estimates of ara-G between adult male and female patients. In children versus adults, the dose-normalized Cmax, time of the Cmax, and the steady-state volume of distribution of ara-G were similar. However, the clearance of ara-G was higher in pediatric patients (0.312 L·h−1·kg−1) as compared with adult patients (0.213 L·h−1·kg−1) (P < .001). The t1/2 of ara-G was shorter in pediatric patients as compared with adult patients (2.1 hours v 3.0 hours; P < .01). CONCLUSION: Nelarabine is an effective prodrug of ara-G, allowing systemic concentrations of ara-G that result in clinical activity.
Does Locoregional Radiation Therapy Improve Survival in Breast Cancer? A Meta-Analysis
Authors: Whelan Timothy J. , Julian Jim , Wright Jim , Jadad Alejandro R. , Levine Mark L. 
Published: February 2017

PURPOSE: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted. METHODS: Randomized trials published between 1967 and 1999 were identified through MEDLINE database, CancerLit database, and reference lists of relevant articles. Relevant data was abstracted. The results of randomized trials were pooled using meta-analyses to estimate the effect of treatment on any recurrence, locoregional recurrence, and mortality. RESULTS: Eighteen trials that involved a total of 6,367 patients were identified. Most trials included both pre- and postmenopausal women with node-positive breast cancer treated with modified radical mastectomy. The type of systemic therapy received, sites irradiated, techniques used, and doses of radiation delivered varied between trials. Data on toxicity were infrequently reported. Radiation was shown to reduce the risk of any recurrence (odds ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.83), local recurrence (odds ratio, 0.25; 95% CI, 0.19 to 0.34), and mortality (odds ratio, 0.83; 95% CI, 0.74 to 0.94). CONCLUSION: Locoregional radiation after surgery in patients treated with systemic therapy reduced mortality. Several questions remain on how these results should be translated into current-day clinical practice.
Therapeutic Relevance of CD34 Cell Dose in Blood Cell Transplantation for Cancer Therapy
Authors: Siena Salvatore , Schiavo Roberta , Pedrazzoli Paolo , Carlo-Stella Carmelo 
Published: February 2017

PURPOSE: To review recent advances in peripheral-blood progenitor-cell (PBPC) transplantation in order to define the optimal cell dose required for autologous and allogeneic transplantation. MATERIALS AND METHODS: A search of MEDLINE was conducted to identify relevant publications. Their bibliographies were also used to identify further articles and abstracts for critical review. RESULTS: The CD34+ cell content of a graft is regarded as an accurate predictor of engraftment success. Postchemotherapy autologous PBPC transplantation with ≥ 5 × 106 CD34+ cells/kg body weight leads to more rapid engraftment than does transplantation of lower cell doses. Further increases in transplant cell dose further accelerate platelet but not neutrophil engraftment. Evidence that long-term hematopoietic recovery may be more accurately predicted by the subpopulation of primitive progenitors transplanted suggests that the content of CD34+CD33− and long-term culture-initiating cells in cell collection samples may be important for predicting successful engraftment, particularly in patients with poor mobilization. Allogeneic transplantation has been limited by concerns regarding graft-versus-host disease and the use of hematopoietic growth factors in donors. The risk of graft rejection and engraftment failure after HLA-mismatched allogeneic transplantation may be overcome by intensive chemoradiotherapy and the infusion of large numbers of T cell–depleted hematopoietic stem cells. CONCLUSION: An optimal cell dose of ≥ 8 × 106 CD34+ cells/kg seems to be recommended for autologous PBPC transplantation. This dose facilitates the administration of scheduled chemotherapy on time and reduces the demand for other supportive therapies. A combination of growth factors may enable patients with poor mobilization to achieve a collection sufficient to allow transplantation. The optimum PBPC dose for allogeneic transplantation remains to be defined.
Burdens and Benefits of Adjuvant Cyclophosphamide, Methotrexate, and Fluorouracil and Tamoxifen for Elderly Patients With Breast Cancer: The International Breast Cancer Study Group Trial VII
Authors: Crivellari Diana , Bonetti Marco , Castiglione-Gertsch Monica , Gelber Richard D. , Rudenstam Carl-Magnus , Thürlimann Beat , Price Karen N. , Coates Alan S. , Hürny Christoph , Bernhard Jürg , Lindtner Jurij , Collins John , Senn Hans-Jörg , Cavalli Franco , Forbes John , Gudgeon Anne , Simoncini Edda , Cortes-Funes Hernan , Veronesi Andrea , Fey Martin , Goldhirsch Aron ,   for the International Breast Cancer Study Group
Published: February 2017

PURPOSE: Information on the tolerability and efficacy of adjuvant chemoendocrine therapy for older women is limited. We studied these issues using the data collected as part of the International Breast Cancer Study Group Trial VII. PATIENTS AND METHODS: Postmenopausal women with operable, node-positive breast cancer were randomized to receive either tamoxifen alone for 5 years (306 patients) or tamoxifen plus three consecutive cycles of classical cyclophosphamide (100 mg/m2 orally days 1 to 14), methotrexate (40 mg/m2 intravenous days 1 and 8), and fluorouracil (600 mg/m2 intravenous days 1 and 8) every 28 days (CMF; 302 patients). The median follow-up was 8.0 years. RESULTS: Among the 299 patients who received at least one dose of CMF, women 65 years of age or older (n = 76) had higher grades of toxicity compared with women less than 65 years old (n = 223) (P = .004). More women in the older age group compared with the younger women experienced grade 3 toxicity of any type (17% v 7%, respectively), grade 3 hematologic toxicity (9% v 5%, respectively), and grade 3 mucosal toxicity (4% v 1%, respectively). Older patients also received less than their expected CMF dose compared with younger postmenopausal women (P = .0008). The subjective burdens of treatment, however, were similar for younger and older patients based on quality-of-life measures (performance status, coping, physical well-being, mood, and appetite). For older patients, the 5-year disease-free survival (DFS) rates were 63% for CMF plus tamoxifen and 61% for tamoxifen alone (hazards ratio [HR], 1.00; 95% confidence interval [CI], 0.65 to 1.52; P = .99). For younger patients, the corresponding 5-year DFS rates were 61% and 53% (HR, 0.70; 95% CI, 0.53 to 0.91; P = .008), but the test for heterogeneity of CMF effect according to age group was not statistically significant. The reduced effectiveness of CMF among older women could not be attributed to dose reductions according to dose received. CONCLUSION: CMF tolerability and effectiveness were both reduced for older patients compared with younger postmenopausal node-positive breast cancer patients who received tamoxifen for 5 years. The development and evaluation of less toxic and more effective chemotherapy regimens are required for high-risk elderly patients.
Correlation of Vascular Endothelial Growth Factor Content With Recurrences, Survival, and First Relapse Site in Primary Node-Positive Breast Carcinoma After Adjuvant Treatment
Authors: Linderholm Barbro , Grankvist Kjell , Wilking Nils , Johansson Mikael , Tavelin Björn , Henriksson Roger 
Published: February 2017

PURPOSE: To determine the predictive value of vascular endothelial growth factor (VEGF) for relapse-free survival (RFS) and overall survival (OS) in primary node-positive breast cancer (NPBC) after adjuvant endocrine treatment or adjuvant chemotherapy. MATERIALS AND METHODS: VEGF was quantitatively measured in tumor cytosols from 362 consecutive patients with primary NPBC using an enzyme immunoassay for human VEGF165. Adjuvant treatment was given to all patients, either as endocrine therapy (n = 250) or chemotherapy (n = 112). The median follow-up time was 56 months. RESULTS: Univariate analysis showed VEGF to be a significant predictor of RFS (P = .0289) and OS (P = .0004) in the total patient population and in patients who received adjuvant endocrine treatment (RFS, P = .0238; OS, P = .0121). In the group of patients who received adjuvant chemotherapy, no significant difference was seen in RFS, but a difference was seen in OS (P = .0235). Patients with bone recurrences tended to have lower VEGF expression (median, 2.17 pg/μg DNA) than patients with visceral metastasis (4.41 pg/μg), brain metastasis (8.29 pg/μg), or soft tissue recurrences (3.16 pg/μg). Multivariate analysis showed nodal status (P = .0004), estrogen receptor (ER) status (P < .0001), and tumor size (P = .0085) to be independent predictors of RFS. VEGF was found to be an independent predictor of OS (P = .0170; relative risk [RR] = 1.82), as were ER (P < .0001; RR = 5.19) and nodal status (P = .0002; RR = 2.58). For patients receiving adjuvant endocrine treatment, multivariate analysis showed VEGF content to be an independent predictor of OS (P = .0420; RR = 1.90) but not of RFS. CONCLUSION: The results suggest that VEGF165 content in tumor cytosols is a predictor of RFS and OS in primary NPBC. VEGF content might also predict outcome after adjuvant endocrine treatment, but further studies in a prospective setting with homologous treatments are required.
Response of Circulating Tumor Cells to Systemic Therapy in Patients With Metastatic Breast Cancer: Comparison of Quantitative Polymerase Chain Reaction and Immunocytochemical Techniques
Authors: Smith Brendan M. , Slade Martin J. , English Jacqueline , Graham Helen , Lüchtenborg Margreet , Sinnett H. Dudley , Cross Nicholas C. P. , Coombes R. Charles 
Published: February 2017

PURPOSE: We previously developed a quantitative system for the detection of cytokeratin 19 (CK-19) transcripts using reverse transcriptase polymerase chain reaction (PCR) to detect breast carcinoma cells in blood and bone marrow. The aim of this study was to determine the value of this system in monitoring patients with metastatic disease and to compare it with an established immunocytochemical method. PATIENTS AND METHODS: Patients with progressive, locally advanced, and metastatic breast cancer (all stage IV) who were due to start systemic treatment were recruited. Blood samples were analyzed for CK-19 transcripts using quantitative PCR (QPCR) and immunocytochemistry (ICC) throughout their course of treatment. RESULTS: One hundred forty-five blood samples were obtained from 22 patients over 13 months. Seventy-two (49.6%) of these samples were positive by QPCR, and 56 (42%) of 133 were positive by ICC. Of the 133 specimens analyzed by both techniques, 95 (71.4%) had the same results for each, and of the 71 samples that were positive, 40 (56%) were positive by both methods. The relationship between the number of cells detected and the QPCR values was statistically significant (P < .0001). Of the 25 courses of assessable treatment, 17 (68%) of 25 treatment outcomes (either response or disease progression) were reflected by QPCR measurements, and 12 (57%) of 21 were reflected by ICC. During the course of the study, five patients showed a response, and of these, ICC was in agreement in four cases (80%) and QPCR in three cases (60%). Eighteen courses of treatment resulted in progression of the disease; however, only 15 of these were assessable by ICC. ICC was in agreement in eight (53%) of 15 of these cases, and QPCR in 15 (83%) of 18 cases. CONCLUSION: Circulating carcinoma cells are frequently found in patients with metastatic breast cancer. In the majority of patients, cancer cell numbers as evaluated by QPCR or ICC reflected the outcome of systemic treatment.
p53 Alterations Predict Tumor Response to Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Prospective Series
Authors: Cabelguenne Arnauld , Blons Hélène , de Waziers Isabelle , Carnot Françoise , Houllier Anne-Marie , Soussi Thierry , Brasnu Daniel , Beaune Phillipe , Laccourreye Ollivier , Laurent-Puig Pierre 
Published: February 2017

PURPOSE: The tumor suppressor gene p53 plays a crucial role in cell cycle control and apoptosis in response to DNA damages. p53 gene mutations and allelic losses at 17p are one of the most common genetic alterations in primary head and neck squamous cell carcinoma (HNSCC). Alterations of the p53 gene have been shown to contribute to carcinogenesis and drug resistance. PATIENTS AND METHODS: In this prospective series, patients with HNSCC were treated with cisplatin-fluorouracil neoadjuvant chemotherapy. p53 status was characterized in 106 patients with HNSCC (p53 mutations, allelic losses at p53 locus, and plasma anti-p53 antibodies) to determine the existence of a relationship between p53 gene status and response to neoadjuvant chemotherapy. RESULTS: Exons 4 to 9 of the p53 gene were analyzed, and mutations were found in 72 of 106 patients with HNSCC. p53 mutations were associated with loss of heterozygosity at chromosome 17p (P < .001). The prevalence of p53-mutated tumors was higher in the group of patients with nonresponse to neoadjuvant chemotherapy than in the group of responders (81% v 61%, respectively; P < .04). When compiling p53 mutations and anti-p53 antibodies in plasma, the correlation between p53 status and response to chemotherapy was significant (87% v 57%, respectively; P = .003). A multivariate analysis showed that p53 status is an independent predictive factor of response to chemotherapy. CONCLUSION: This prospective study suggests that p53 status may be a useful indicator of response to neoadjuvant chemotherapy in HNSCC.
Post Hoc Economic Analysis of Temozolomide Versus Dacarbazine in the Treatment of Advanced Metastatic Melanoma
Authors: Hillner Bruce E. , Agarwala Sanjiv , Middleton Mark R. 
Published: February 2017

PURPOSE: To determine the potential economic implications resulting from oral temozolomide (TEM) compared with intravenous (IV) dacarbazine (DTIC) for metastatic melanoma. PATIENTS AND METHODS: We performed a cost-effectiveness (CE) analysis using hazard ratios (HRs) from the phase III (Schering I95–018) trial comparing TEM 200 mg/m2/d orally for 5 days every 28 days with DTIC 250 mg/m2/d IV for 5 days every 21 days. Sensitivity analyses assessed a range of TEM’s efficacy and costs, direct nonmedical costs, and the DTIC schedule. RESULTS: The trial found an overall survival trend favoring TEM; median survival times of patients treated with DTIC and TEM were 6.4 and 7.7 months, respectively (HR = 1.18; 95% confidence interval [CI], 0.92 to 1.52; intention to treat, P = .20). The mean increase in survival of TEM over DTIC was 1.1 months. The projected average costs per patient were greater with TEM than DTIC ($6,902 v $3,697, respectively). The incremental CE ratio using TEM was $36,990 per life-year or $101 per day of life gained. The CE ratio’s 95% CI ranged from −$65,180 (DTIC is more effective) to $18,670 per year of life gained. The CE ratios decreased 50% if direct nonmedical costs were included and increased 50% if DTIC’s efficacy was unchanged if given as a single daily dosage. Sixty percent of simulations found TEM with a CE threshold of less than $50,000 per life-year gained. CONCLUSION: Although the base-case efficacy of TEM compared with DTIC was not statistically significant, its associated incremental CE would be comparable with many interventions. TEM for metastatic melanoma illustrates the tension confronting providers choosing between similar agents that markedly differ in convenience and costs.