bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flutamide withdrawal syndrome: its impact on clinical trials in hormone-refractory prostate cancer.
Authors: Scher H I , Kelly W K 
Published: February 2017

PURPOSE To evaluate the effect of discontinuation of the antiandrogen, flutamide, in patients with metastatic prostate cancer who are progressing on hormonal therapy. PATIENTS AND METHODS Thirty-six patients with progressive disease on hormonal treatment that included flutamide had discontinuation of the antiandrogen. Thirty-five (95%) had progressive increases in prostate-specific antigen (PSA) levels, despite castrate levels of testosterone. Twenty-five patients (69%) were treated with combined androgen blockade (orchiectomy or gonadotropin-releasing hormone [GnRH] analog plus flutamide) as initial therapy and 11 (31%) were started on monotherapy alone. Patients who had not undergone a previous orchiectomy were continued on the GnRH analog. Patients were monitored clinically and with serial PSA measurements, radionuclide scans, and radiographs as indicated to assess response. RESULTS Considering the 35 patients with increasing PSA values, 10 (29%) showed a significant decline (> or = 80% in seven, and > or = 50% in three) in PSA from baseline. All 10 had received combined androgen blockade as initial therapy. The duration of decline was short (median, 5+ months; range, 2 to 10+), but was associated with improvement in clinical symptoms, while one patient had a partial response in an epidural mass with parallel decline in PSA. None of the patients started on single hormone therapies responded. CONCLUSION Discontinuation of flutamide was associated with a significant decrease in PSA values in 10 of 25 patients (40%; 95% confidence interval, 21% to 59%) and clinical improvement in a subset of patients who had an initial response, but later progressive disease on combined androgen blockade. A trial of flutamide withdrawal should be considered in patients progressing on total androgen blockade before the initiation of more toxic therapies. It is likely that flutamide withdrawal has contributed to the observed responses in phase II trials of both second-line hormonal therapies and new cytotoxic agents. Future phase II trials in hormone-refractory prostatic cancer must control for this observation, and insure that progression off flutamide is documented before initiation of alternative treatment.
Human immunodeficiency virus-associated systemic lymphomas may be subdivided into two main groups according to Epstein-Barr viral latent gene expression.
Authors: Carbone A , Tirelli U , Gloghini A , Volpe R , Boiocchi M 
Published: February 2017

PURPOSE We report a pathologic characterization of human immunodeficiency virus (HIV)-associated systemic lymphomas, including the association of Epstein-Barr virus (EBV) in different categories. PATIENTS AND METHODS Eighty-seven HIV-associated non-Hodgkin's lymphoma (NHL) were classified according to classic NHL classification and a recent description of morphologic variants of high-grade B-cell NHL. Seventy-one cases were immunophenotypically-genotypically characterized, whereas, in 49 representative cases, the association of EBV was assessed by nonisotopic in situ hybridization (ISH) and the immunohistochemical demonstration of latent membrane protein-1 (LMP-1). In addition, 14 Hodgkin's disease (HD) cases, occurring in patients with HIV infection, were investigated for the frequency of LMP-1 expression. RESULTS Most lymphomas were of B-cell derivation and showed a blastic cell morphology, with (1) small noncleaved cells (SNCCs; 36 cases), (2) large noncleaved cells (10 cases), and (3) immunoblasts, usually polymorphic (12 cases). Moreover, 12 cases were classified as anaplastic large-cell (ALC) Ki-1-positive (Ki-1+) lymphoma. Combined ISH studies (for viral DNA and EBV RNA [EBER]) and immunohistologic demonstration of LMP-1 suggested that there were differences in viral latent gene expression between ALC Ki-1+ or immunoblastic lymphomas (usually EBV+, LMP-1+), and EBV-infected cells of SNCC lymphomas, which did not show LMP-1 expression. A high proportion (10 of 14) of LMP-1+ HD cases was found. CONCLUSION Differences in EBV association and LMP-1 expression were found between a major group of HIV-associated systemic NHL with blastic cell morphology, including SNCC lymphoma and its variants, and anaplastic cell lymphomas. A proportion of immunoblastic (polymorphic) lymphomas was different in viral latent gene expression from other blastic cell systemic lymphomas. It is concluded that only a group of these lymphomas (most ALC Ki-1+ and HD cases, along with a nonnegligible fraction of immunoblastic lymphomas) seems to be linked etiopathologically to EBV.
Pathologic complete response in advanced non-small-cell lung cancer following preoperative chemotherapy: implications for the design of future non-small-cell lung cancer combined modality trials.
Authors: Pisters K M , Kris M G , Gralla R J , Zaman M B , Heelan R T , Martini N 
Published: February 2017

PURPOSE This report determines the incidence of pathologic complete response in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with mitomycin, vinca alkaloid, and high-dose cisplatin (MVP) chemotherapy, and estimates the effect of MVP on survival. PATIENTS AND METHODS We have identified and reviewed the course of 21 patients with advanced NSCLC who achieved a pathologic complete response following a median of three preoperative MVP combination chemotherapy courses including vinblastine or vindesine, cisplatin (120 mg/m2), and mitomycin (n = 19). RESULTS All patients had a major objective response following preoperative chemotherapy and nine (43%) had a clinical complete response. Nine patients with pathologic complete responses were among 73 entered on a preoperative chemotherapy program, yielding an incidence estimate of 12% (95% confidence interval, 6% to 22%). The median survival duration for all 21 patients has not been reached. The median follow-up duration is now 68 months (range, 17 to 109). Survival estimates are 90% at 1 year, 62% at 3 years, and 54% at 5 years. Nine patients have relapsed with initial sites of recurrence as follows: brain (n = 5), other systemic sites (n = 3), and locoregional (n = 1). One patient died in the postoperative period. Eleven patients remain disease-free and all have excellent functional status. CONCLUSION We have observed pathologic complete responses in approximately 12% of advanced NSCLC patients treated with preoperative MVP chemotherapy. These pathologically determined responses were seen only in patients with major objective responses clinically. Pathologic complete response predicts excellent survival and functional level and should be considered a major end point in the evaluation of preoperative chemotherapy programs.
Comparative pharmacokinetic studies of three asparaginase preparations.
Authors: Asselin B L , Whitin J C , Coppola D J , Rupp I P , Sallan S E , Cohen H J 
Published: February 2017

PURPOSE As part of pharmacologic studies of asparaginase (ASNase), we determined the half-life of ASNase activity and protein, and the effect of dose, repeated doses, different drug preparations, and hypersensitivity reactions on the half-life (t1/2) of serum ASNase activity. PATIENTS AND METHODS We measured ASNase activity (spectrophotometric assay) in serum samples obtained from patients with acute lymphoblastic leukemia (ALL) at various times during their therapy with intramuscular ASNase. ASNase protein was measured by enzyme-linked immunoadsorbent assay (ELISA). RESULTS Studies following the initial dose of Escherichia coli-derived ASNase demonstrated no difference in apparent t1/2 following 25,000 IU/m2 versus 2,500 IU/m2 (1.24 v 1.35 days, P = .2). The apparent t1/2s following maintenance doses of E coli ASNase (middle dose t1/2, 1.28 days, or last dose t1/2, 1.14 days) showed no difference when compared with the initial dose of ASNase (P = .3 to .9). There was no significant difference between the apparent t1/2s of ASNase activity and ASNase protein (n = 8, P = .2 to .6). The serum t1/2 was 0.65 and 5.73 days for patients receiving Erwinia or polyethylene glycol (PEG)-modified E coli ASNase, respectively, as the induction dose. ASNase activity was undetectable in sera of four patients studied in the week following an anaphylactic reaction to E coli ASNase and the t1/2 was significantly shorter in five patients with a history of allergic reaction to E coli ASNase who were studied following a dose of PEG ASNase, (t1/2, 1.80 days). CONCLUSION We conclude that (1) the apparent t1/2 of ASNase is dependent on enzyme preparation used, but is not affected by dose or by repeated use; (2) the apparent t1/2 of E coli ASNase as a protein is the same as the apparent t1/2 of enzymatic activity; and (3) patients who have had a hypersensitivity reaction to E coli ASNase have a decreased apparent t1/2 with both E coli and PEG ASNase.
Phase I clinical trial of carboplatin and 41.8 degrees C whole-body hyperthermia in cancer patients.
Authors: Robins H I , Cohen J D , Schmitt C L , Tutsch K D , Feierabend C , Arzoomanian R Z , Alberti D , d'Oleire F , Longo W , Heiss C 
Published: February 2017

PURPOSE To evaluate the biologic interactions and toxicities of carboplatin combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes in a phase I clinical trial. PATIENTS AND METHODS Thirty assessable patients with cancer refractory to conventional therapy were treated. During induction therapy, patients received WBH alone in week 1, WBH plus carboplatin in week 2, and carboplatin alone in week 5. Carboplatin dose was escalated (three patients per group) as follows: 100, 150, 200, 250, 300, 350, 400, 480, and 575 mg/m2; three additional patients were entered at 480 mg/m2. Carboplatin was administered at target temperature. RESULTS Comparisons of the mean/median WBC and platelet nadirs for carboplatin alone and carboplatin plus WBH demonstrated no enhancing effect by WBH. Toxicities including nausea and/or vomiting, as well as myelosuppression, were within acceptable limits, allowing for escalation to a dose of 575 mg/m2; three of three patients at this dose level experienced grade 4 myelosuppression with no associated infection or bleeding. No renal toxicity was observed. Analysis of platinum in plasma ultrafiltrate and urine showed only slight effects of WBH on the pharmacokinetics and renal excretion of platinum. Responses included the following: lung--minor response (200 mg/m2); gastrointestinal neuroendocrine--complete response (CR) (400 mg/m2); pancreatic--partial response (PR) (480 mg/m2); small bowel--PR (575 mg/m2); ovarian--CR, two patients (575 mg/m2), with marker data suggesting WBH enhancement of carboplatin cytotoxicity. Another three patients experienced clinical improvement after WBH plus carboplatin, but progression with carboplatin alone (lung, 400 mg/m2; gastrointestinal neuroendocrine, 480 mg/m2; melanoma, 480 mg/m2). CONCLUSION We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies.
Escalating dose of mitoxantrone with high-dose cyclophosphamide, carmustine, and etoposide in patients with refractory lymphoma undergoing autologous bone marrow transplantation.
Authors: Attal M , Canal P , Schlaifer D , Chatelut E , Dezeuze A , Huguet F , Payen C , Pris J , Laurent G 
Published: February 2017

PURPOSE We conducted a dose-finding study of mitoxantrone (MITO) in combination with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) in refractory lymphoma undergoing autologous bone marrow transplantation (ABMT). The objective were to determine the following: (1) the maximum-tolerated dose of MITO, (2) the extramedullary toxicity of this regimen, (3) its antitumor activity, and (4) the pharmacokinetic characteristics of MITO at each dose level. PATIENTS AND METHODS Escalating doses of MITO (15 to 90 mg/m2, single bolus infusion on day -8) followed by CBV were administered to 20 patients (mean age, 38.5 years) with refractory lymphoma. MITO concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS No toxic death occurred. The maximum-tolerated dose appears to be 75 mg/m2. Two of five patients treated with 90 mg/m2 developed severe organ toxicity, versus zero of 15 treated with doses up to 75 mg/m2. Duration of neutropenia was longer for patients treated with 90 mg/m2 (31.7 days) than for patients treated with doses up to 75 mg/m2 (22.1 days) (P < .05). A linear relationship was observed between administered dose of MITO and (1) plasma peak value, (2) area under the curve (AUC), and (3) plasma concentration on the day of marrow infusion (day 0). Hematologic toxicity was related to the terminal half-life (T1/2) of MITO, and day-0 plasma concentration. A high complete response (CR) rate was observed (60%), and eight of 11 (73%) patients treated with MITO > or = 60 mg/m2 achieved a CR. CONCLUSION MITO (up to 75 mg/m2) and CBV can be administered with acceptable toxicity and a promising CR rate in this poor-risk population, justifying further phase II studies.
Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.
Authors: Goldberg R M , Loprinzi C L , O'Fallon J R , Veeder M H , Miser A W , Mailliard J A , Michalak J C , Dose A M , Rowland K M , Burnham N L 
Published: February 2017

PURPOSE To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer. PATIENTS AND METHODS A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study. RESULTS Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P < .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05). CONCLUSION Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.
The cancer anorexia-cachexia syndrome.
Authors: Nelson K A , Walsh D , Sheehan F A 
Published: February 2017

PURPOSE To review the research related to the anorexia-cachexia syndrome in patients with cancer, with attention to the etiology and symptomatic treatment. DESIGN A comprehensive literature review using MEDLINE. RESULTS AND CONCLUSION The anorexia-cachexia syndrome is a common problem in advanced cancer. Although many possible etiologies have been investigated, the cause has not been determined. Appropriate clinical evaluation is necessary to identify those patients who may respond to available, symptomatic treatments.
Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer.
Authors: Ihde D C , Mulshine J L , Kramer B S , Steinberg S M , Linnoila R I , Gazdar A F , Edison M , Phelps R M , Lesar M , Phares J C 
Published: February 2017

PURPOSE We performed a prospective randomized clinical trial to determine whether higher doses of etoposide and cisplatin (EP) yield more complete responses or longer survival in small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS Ninety patients with previously untreated extensive-stage SCLC fulfilled criteria for randomization to standard-dose versus high-dose EP. Another 25 patients at risk of excessive toxicity from high-dose treatment were given standard-dose therapy. During cycles 1 and 2 of EP, patients on standard-dose treatment received intravenous etoposide 80 mg/m2 on days 1 to 3 and cisplatin 80 mg/m2 on day 1 every 3 weeks; high-dose treatment consisted of etoposide 80 mg/m2 on days 1 to 5 and cisplatin 27 mg/m2 on days 1 to 5 every 3 weeks. All patients received standard-dose EP in cycles 3 and 4. In cycles 5 through 8, completely responding patients continued standard-dose EP; all other patients received either cyclophosphamide, doxorubicin, and vincristine, or (if possible) a combination drug program based on in vitro drug sensitivity testing of tumor-cell lines established from individual patients. RESULTS Despite 68% higher doses and a 46% higher dose-rate intensity actually given to patients randomized to receive high-dose relative to those randomized to receive standard-dose EP, complete response rates (23% v 22%; P = .99) and median survival durations (10.7 and 11.4 months, respectively; P = .68) were virtually identical. Complete responses occurred in 4% of patients and the median survival duration was 5.8 months in nonrandomized patients. Leukopenia (P < .0001), thrombocytopenia (P < .0001), febrile neutropenia (P = .01), and weight loss (P = .02) were significantly more common in patients randomized to receive high-dose compared with standard-dose EP. CONCLUSION No therapeutic benefits resulted from increasing planned doses by 67% for the first two cycles of EP in patients with extensive-stage SCLC. Higher doses were associated with substantially worse toxicities.
p53 nuclear overexpression: an independent predictor of survival in lymph node--positive colorectal cancer patients.
Authors: Zeng Z S , Sarkis A S , Zhang Z F , Klimstra D S , Charytonowicz E , Guillem J G , Cordon-Cardo C , Cohen A M 
Published: February 2017

PURPOSE This study was performed to determine the prognostic significance of p53 gene overexpression in a homogeneous group of node-positive colorectal cancer patients. MATERIALS AND METHODS Paraffin sections from the primary tumors in 107 colorectal cancer patients who had preoperative serum carcinoembryonic antigen (CEA) levels less than five were examined for the expression of p53 nuclear protein by immunohistochemical staining using the monoclonal antibody PAb 1801. The nuclear p53 overexpression was compared with clinicopathologic variables and follow-up data. RESULTS Positive staining was not observed in normal colorectal mucosal cells. Specific p53 nuclear staining was detected in primary tumor from 50 patients (46.7%). p53 nuclear overexpression was not significantly correlated with patients' sex, age, tumor location, differentiation, T stage, N stage, and lymphatic and/or vascular vessel invasion. With a median follow-up of 61.7 months, 60% of the p53-positive patients have had disease recurrence, versus only 35% of the p53-negative group (P = .02). Forty-two percent of the p53-positive patients died of colorectal cancer compared with 21.1% of the p53-negative patients (P = .03). By multivariate analysis, p53 overexpression was found to be an independent predictor for disease-free and disease-specific survival. CONCLUSION In node-positive colorectal cancer patients with low preoperative CEA levels, nuclear p53 overexpression as determined by immunohistochemistry on archived tissue is an independent predictor for prognosis.
Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin.
Authors: Navari R M , Kaplan H G , Gralla R J , Grunberg S M , Palmer R , Fitts D 
Published: February 2017

PURPOSE To assess the antiemetic effects and safety profile of four different doses of granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) when administered as a single intravenous (IV) dose for prophylaxis of cisplatin-induced nausea and vomiting. PATIENTS AND METHODS One hundred eighty-four chemotherapy-naive patients receiving high-dose cisplatin (81 to 120 mg/m2) were randomized to receive one of four granisetron doses (5, 10, 20, or 40 micrograms/kg) administered before chemotherapy. Patients were observed on an inpatient basis for 18 to 24 hours, and vital signs, nausea, vomiting, retching, and appetite were assessed. Safety analyses included incidence of adverse experiences and laboratory parameter changes. RESULTS After granisetron doses of 5, 10, 20, and 40 micrograms/kg, a major response (< or = two vomiting or retching episodes, and no antiemetic rescue) was recorded in 23%, 57%, 58%, and 60% of patients, respectively, and a complete response (no vomiting or retching, and no antiemetic rescue) in 18%, 41%, 40%, and 47% of patients, respectively. There was a statistically longer time to first episode of nausea (P = .0015) and vomiting (P = .0001), and fewer patients were administered additional antiemetic medication in the 10-micrograms/kg dosing groups than in the 5-micrograms/kg dosing group. As granisetron dose increased, appetite return increased (P = .040). Headache was the most frequently reported adverse event (20%). CONCLUSION A single 10-, 20-, or 40-micrograms/kg dose of granisetron was effective in controlling vomiting in 57% to 60% of patients who received cisplatin at doses greater than 81 mg/m2 and totally prevented vomiting in 40% to 47% of patients. There were no statistically significant differences in efficacy between the 10-micrograms/kg dose and the 20- and 40-micrograms/kg doses. Granisetron was well tolerated at all doses.
Combination chemotherapy, glucocorticoids, and interferon alfa in the treatment of multiple myeloma: a Southwest Oncology Group study.
Authors: Salmon S E , Crowley J J , Grogan T M , Finley P , Pugh R P , Barlogie B 
Published: February 2017

PURPOSE Standard therapy for multiple myeloma consists of cytotoxic chemotherapy plus glucocorticoids. Interferon (IFN) alfa maintenance is reported to prolong chemotherapy-induced remissions and survival. This study evaluates induction chemotherapy, glucocorticoids, and interferon maintenance in myeloma. PATIENTS AND METHODS Five hundred twenty-two previously untreated myeloma patients were randomized to three chemotherapy regimens with differing glucocorticoid intensities. Patients who achieved remission were randomized to receive IFN or observation until relapse. Patients who failed to respond to chemotherapy received IFN alfa plus dexamethasone (DEX). RESULTS Five hundred nine patients were eligible for induction chemotherapy. Chemotherapy with higher dose-intensity glucocorticoids yielded higher response rates and improved survival (P = .02 for the three-group comparison; P < .05 for each higher glucocorticoid arm v vincristine, melphalan, cyclophosphamide, and prednisone alternating with vincristine, carmustine [BCNU], doxorubicin, and prednisone [VMCP/VBAP]). One hundred ninety-three patients who achieved remission were randomized to receive IFN alfa 3 MU three times weekly or observation. IFN was not superior to observation for relapse-free (P = .95) or overall survival (P = .39) from start of maintenance. Eighty-eight induction failures received 5 MU of IFN three times weekly plus DEX. Patients who received IFN/DEX had a median survival duration of 48 months from start of IFN/DEX. CONCLUSION Higher-dose glucocorticoids increases frequency of response to chemotherapy and prolong survival in myeloma. IFN maintenance with the dose schedule used in this trial did not prolong relapse-free or overall survival. We cannot exclude a small effect of IFN, as most individual trials do not have sufficient statistical power. Meta-analysis of randomized trials evaluating IFN maintenance in myeloma might be of value. While IFN appeared ineffective, addition of higher-dose glucocorticoids improved outcome in myeloma.