bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of ketoconazole combined with weekly doxorubicin in patients with androgen-independent prostate cancer.
Authors: Sella A , Kilbourn R , Amato R , Bui C , Zukiwski A A , Ellerhorst J , Logothetis C J 
Published: February 2017

PURPOSE A phase II clinical trial was performed to assess the antitumor activity and toxicity of ketoconazole in combination with doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) in patients with androgen-independent prostate cancer (AI PCa). PATIENTS AND METHODS Thirty-nine consecutive patients whose disease progressed following castration were treated with oral ketoconazole (1,200 mg) daily and Adriamycin (20 mg/m2 in a 24-hour infusion) once weekly. Antitumor activity was assessed by the level of prostatic-specific antigen (PSA) decline. RESULTS PSA levels decreased > or = 50% from baseline in 21 (55%; 95% confidence interval, 38% to 71%) of 38 assessable patients. We observed partial responses (PRs) in seven (58%) of 12 patients with measurable soft tissue disease (in the lung, lymph nodes, and liver). Two patients with history of atherosclerotic heart disease had a sudden cardiac death. Serious toxic reactions included grade III to V stomatitis and grade III to IV acral erythema in 11 patients (29%), and grade III to IV anal and urethral mucositis in five patients (13%). Grade III to IV neutropenia occurred in 11 patients (29%). Seventeen patients (45%) required hospitalization for complications. Fifteen patients (39%) developed hypokalemia, and 24 patients (63%) developed clinical adrenal insufficiency. CONCLUSION The combination of ketoconazole and Adriamycin has a 55% PSA response rate in patients with AI PCa and is worthy of additional study. This treatment results in frequent adrenal insufficiency. Therefore, future studies should incorporate routine corticosteroid replacement. The cardiac complications caused by this combination should be studied further before it is widely used.
Detection of cells bearing the t(14;18) translocation following myeloablative treatment and autologous bone marrow transplantation for follicular lymphoma.
Authors: Johnson P W , Price C G , Smith T , Cotter F E , Meerabux J , Rohatiner A Z , Young B D , Lister T A 
Published: February 2017

PURPOSE To use the polymerase chain reaction (PCR) technique for molecular assessment of the results of myeloablative treatment of follicular lymphoma with autologous bone marrow transplantation. PATIENTS AND METHODS Seventy-six patients with follicular or transformed follicular lymphoma were treated with cyclophosphamide 60 mg/kg x 2 and total-body irradiation 12 Gy, supported by autologous bone marrow transplantation. The bone marrow mononuclear cell fraction was treated in vitro with CD20 monoclonal antibody and baby rabbit complement. The PCR technique was used to identify 50 patients with amplifiable t(14; 18) translocations in biopsy material from lymph nodes or bone marrow infiltrated by lymphoma. RESULTS Following treatment of the harvested bone marrow in vitro, 29 samples were tested by PCR to assess the efficacy of purging. In 25 cases, the same t(14; 18) sequences were amplified as from the patients' original biopsies, while in four cases, the marrow became PCR-negative. Three of the four patients treated with PCR-negative marrow subsequently developed recurrent lymphoma, compared with 11 of 25 in the PCR-positive group. Bone marrow and peripheral-blood mononuclear cell samples from 27 patients were studied during the follow-up period. All but one had the presence of the lymphoma-related t(14; 18) clone detectable by PCR and confirmed by direct sequencing from at least one sample between 3 months and 7 years after reinfusion of the bone marrow. With a median follow-up duration of 3 years, 13 patients developed recurrent disease, 13 remained in remission with the t(14; 18) still detectable, and one died of acute myeloid leukemia. CONCLUSION This form of therapy does not eliminate the lymphoma-related t(14; 18)-bearing clone of cells, although the significance of its continued presence is uncertain. Improved methods for both treatment of the bone marrow in vitro and treatment of the lymphoma in vivo are required.
Prediction of systemic fungal infection in allogeneic marrow recipients: impact of amphotericin prophylaxis in high-risk patients.
Authors: O'Donnell M R , Schmidt G M , Tegtmeier B R , Faucett C , Fahey J L , Ito J , Nademanee A , Niland J , Parker P , Smith E P 
Published: February 2017

PURPOSE To identify risk factors that might predict for systemic fungal infections in marrow transplant recipients within the first 100 days and to assess the efficacy of low-dose amphotericin B used as prophylaxis for candidemia and infection with invasive Aspergillus species in patients at risk. PATIENTS AND METHODS A retrospective analysis of transplant outcomes for 331 allogeneic marrow recipients transplanted between 1983 and 1989 was performed to identify patients who might be at increased risk of fungal infection. Factors analyzed included disease, remission status, transplant regimen, graft-versus-host disease (GVHD) prophylaxis, duration of neutropenia, and development of GVHD. A trial of low-dose amphotericin (5 to 10 mg/d) begun on day +1 and continuing for 2 to 3 months posttransplant was begun in 1987 to evaluate its utility in reducing systemic mycoses. RESULTS There were 18 episodes of candidemia and 18 systemic mycoses documented by blood or tissue culture or by biopsy. The initiation of high-dose (0.5 to 1 mg/kg/d) corticosteroids early as a component of GVHD prophylaxis in 1986 was identified as the most important risk factor for fungal infections, with a sixfold increase in infections as compared with the previous GVHD regimen (P < .0001); this was despite a significant decrease in the incidence of grade II to IV GVHD (7% v 43%; P = .0001). Low-dose amphotericin B initiated before the start of high-dose corticosteroid GVHD prophylaxis reduced the incidence of fungal infections from 30% to 9% (P = .01) without renal toxicity. Cyclosporine levels were lower in the patients who received amphotericin, leading to an increase in the rate of GVHD to 19% (P = .02). Controlling for GVHD prophylaxis, prolonged neutropenia (P = .00), and grade II to IV GVHD (P = .01) were also identified as risk factors for fungal infection. CONCLUSION Amphotericin B can be used in low doses as prophylaxis for fungal infections early in the posttransplant course. However, cyclosporine doses need to be monitored to maintain target levels.
Attitudes about genetic testing for breast-ovarian cancer susceptibility.
Authors: Lerman C , Daly M , Masny A , Balshem A 
Published: February 2017

PURPOSE In anticipation of the availability of genetic testing for a breast-ovarian cancer susceptibility gene (BRCA1), this study examined interest in and expectations about the impact of a potential genetic test. PATIENTS AND METHODS The subjects were 121 first-degree relatives (FDRs) of ovarian cancer patients. The design was cross-sectional. Subjects completed a structured telephone interview of attitudes about cancer and genetic testing, and self-report psychologic questionnaires to assess coping style and mood disturbance. RESULTS Overall, 75% of FDRs said that they would definitely want to be tested for BRCA1 and 20% said they probably would. In bivariate analyses, interest was associated positively with education, perceived likelihood of being a gene carrier, perceived risk of ovarian cancer, ovarian cancer worries, and mood disturbance. In logistic regression analysis, perceived likelihood of being a gene carrier was associated strongly with interest (odds ratio, 3.7; P = .006). Results of stepwise linear regression modeling indicated that an anticipated negative impact of genetic testing was associated with being younger (beta = -.66, P = .009), having more mood disturbance (beta = .015, P = .01), and having an information-seeking coping style (beta = .19, P = .002). CONCLUSION These results suggest that the demand for genetic testing for BRCA1 among FDRs of cancer patients may be great. Moreover, those who elect to participate may represent a more psychologically vulnerable subgroup of high-risk women.
Recombinant human erythropoietin treatment in cisplatin-associated anemia: a randomized, double-blind trial with placebo.
Authors: Cascinu S , Fedeli A , Del Ferro E , Luzi Fedeli S , Catalano G 
Published: February 2017

PURPOSE To evaluate the effect of exogenous recombinant human erythropoietin (rHuEPO) on the increase of hemoglobin levels and on the transfusion requirements in patients with cisplatin (CDDP)-induced anemia, we performed a double-blind randomized trial with placebo. PATIENTS AND METHODS One hundred patients with CDDP-associated anemia (hemoglobin level < 90 g/L) were randomized to receive either placebo (saline solution) or rHuEPO (100 U/kg body weight subcutaneously) three times per week. The end points of this study were the increase in hemoglobin levels to greater than 100 g/L after 3, 6, and 9 weeks and the effect on transfusion requirements. RESULTS Ninety-nine of 100 patients were assessable for response and toxicity. In the rHuEPO arm, mean hemoglobin levels were statistically significantly increased after the third, sixth, and ninth weeks of therapy (101.1 +/- 9.0, 102.4 +/- 6.6, and 105.1 +/- 9.4 g/L, respectively) compared with the mean baseline value (86.3 +/- 6.2 g/L). In the placebo arm, there were no increases in mean hemoglobin levels at the third, sixth, and ninth weeks (81.0 +/- 5.2, 81.3 +/- 9.2, and 81.2 +/- 11 g/L, respectively) compared with the mean baseline value (87.3 +/- 5.2 g/L). Furthermore only 20% of patients required blood transfusions in the rHuEPO arm versus 56% of patients in the placebo arm (P = .01), with a mean units of blood transfused per patient of 0.30 in the rHuEPO arm and 1.8 in the placebo arm (P = .01). Treatment was well tolerated, with no significant side effects. CONCLUSION CDDP-induced anemia is corrected by rHuEPO, which results in reduced blood transfusion requirements.
Stereotactic radiosurgery: a review and comparison of methods.
Authors: Phillips M H , Stelzer K J , Griffin T W , Mayberg M R , Winn H R 
Published: February 2017

PURPOSE Stereotactic radiosurgery (SRS) is an evolving modality for treating well-circumscribed intracranial lesions. Different physical methods have been developed to deliver highly localized dose distributions accurately. We review the different methods and the documented clinical results to present a coherent view of radiosurgery, and to aid physicians and physicists in the appropriate use of this modality. DESIGN A review of the medical physics and clinical literature was conducted. The physical aspects of the different methods and their impact on treatment were summarized. Results were compiled from those individual clinical series with adequate follow-up data to compare the various modalities with respect to treatment outcome for benign tumors, metastases, and vascular malformations. RESULTS The physical accuracy was comparable between radiosurgical methods. Differences between gamma radiation and linear accelerator methods had little effect on the dose distribution for single isocenter treatments. Charged particle methods could produce better dose localization for large lesions (> 25 cm3) than was possible with photon methods. Clinical results indicate similar lesion control rates between all radiosurgical methods. There was a progressive increase in the median size of treated lesions for gamma radiation, linear accelerator, and charged particle methods. CONCLUSION For small lesions (< 5 cm3), physical dose distributions are similar for the photon methods, but linear accelerator methods offer more flexibility for the treatment of intermediate-sized (5 to 25 cm3) lesions in applying future technical developments. More clinical results are needed before firm conclusions can be drawn on the type of lesions to be treated, and the dose-volume parameters to be used.
Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer.
Authors: Sautner T , Hofbauer F , Depisch D , Schiessel R , Jakesz R 
Published: February 2017

PURPOSE The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor, predominantly due to metastatic spread of the tumor. Depending on the type of tumor histology, the pathway of metastases is mainly peritoneal or hepatic dissemination. Interruption of this mechanism may be possible by intraperitoneal chemotherapy (IPT). PATIENTS AND METHODS In a prospective randomized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer, 33 patients underwent adjuvant postoperative IPT with cisplatin, while 34 control subjects remained untreated. RESULTS Patients in the treatment group received a median of four IPT perfusions. Apart from frequent nausea, no adverse reactions or complications were noted. The median disease-free survival durations were 12.7 months and 9.7 months in treated patients and controls, respectively (P = .8). After a median follow-up duration of 72 months, 54 patients (80%) had died of primary disease or related complications. The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls (P = .6). Autopsies were performed on 12 (18%) of 54 patients who died, and showed tumor spread to the peritoneal cavity and/or to the liver, irrespective of the application of IPT. CONCLUSION IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer. The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent, an inefficient modus of application, or a lack of sufficient drug penetration into the serosa or peritoneal metastasis.
Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer.
Authors: Loprinzi C L , Kuross S A , O'Fallon J R , Gesme D H , Gerstner J B , Rospond R M , Cobau C D , Goldberg R M 
Published: February 2017

PURPOSE Hydrazine sulfate is a controversial agent that was originally studied in cancer patients approximately 20 years ago. Based on a series of recent trials that suggested that this drug might have utility in cancer patients, we conducted this study. PATIENTS AND METHODS Patients with metastatic colorectal cancer were randomized to receive hydrazine sulfate or placebo in a double-blinded manner. Protocol patients did not concurrently receive any other systemic antineoplastic treatment. RESULTS There were 127 assessable patients entered onto this clinical trial. Data from the study showed trends both for poorer survival and for poorer quality of life (QL) in the hydrazine group. There were no significant differences in the two study arms with regard to anorexia or weight loss. CONCLUSION This trial failed to demonstrate any benefit for hydrazine sulfate.
A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma.
Authors: Rusch V , Saltz L , Venkatraman E , Ginsberg R , McCormack P , Burt M , Markman M , Kelsen D 
Published: February 2017

PURPOSE This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy. PATIENTS AND METHODS Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first. RESULTS Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients). CONCLUSION This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control.
ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.
Authors: Velasquez W S , McLaughlin P , Tucker S , Hagemeister F B , Swan F , Rodriguez M A , Romaguera J , Rubenstein E , Cabanillas F 
Published: February 2017

PURPOSE This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.
Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer.
Authors: Fossella F V , Lee J S , Murphy W K , Lippman S M , Calayag M , Pang A , Chasen M , Shin D M , Glisson B , Benner S 
Published: February 2017

PURPOSE We conducted a phase II study to determine the response and toxicity of docetaxel (Taxotere; Rhône-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in chemotherapy-naive patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS We treated 41 chemotherapy-naive patients who had stage IIIb or IV non-small-cell lung cancer with 100 mg/m2 of docetaxel intravenously over 1 hour every 3 weeks. Responses were assessed after every one to two treatment courses. Responses of 39 of 41 patients were assessable. The patient's median age was 63 years; 90% of patients had a Zubrod performance status of 0 or 1. The predominant histology was adenocarcinoma (54%), and 90% of patients had stage IV disease. RESULTS Thirteen patients (33%) achieved a partial response to treatment, and the median response duration was 14 weeks. Grade 3 or 4 neutropenia occurred in 97% of patient; this was usually of brief duration and was associated with serious infection in 17% of patients. Other acute toxic effects included easily treated hypersensitivity reactions (36% of patients) and dermatitis (74%). We also observed fluid retention (with peripheral edema or pleural effusion or both) in 54% of patients. This was a cumulative side effect that generally occurred late in treatment. CONCLUSION Docetaxel administered at 100 mg/m2 intravenously every 3 weeks has significant activity against non-small-cell lung cancer, with a 33% major response rate. Primary toxicities were neutropenia, hypersensitivity, and fluid retention.
Results of a clinical trial in humans with refractory cancer of the intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl, in combination with various single antineoplastic agents.
Authors: Brandes L J , Simons K J , Bracken S P , Warrington R C 
Published: February 2017

PURPOSE We assessed N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE) potentiation of chemotherapy in vitro and performed a pharmacokinetic study and phase I/II trial of DPPE, combined with various single agents, in patients with advanced refractory cancer. PATIENTS AND METHODS In vitro chemopotentiation by DPPE was assessed in drug-sensitive and -resistant (multidrug resistant-positive [MDR+]) human tumor cells using a colony survival assay. The effect of DPPE and verapamil on the intracellular concentration of daunorubicin in MDR+ cells was compared. For the clinical study, subjects with progressive malignancy received a weekly infusion of a maximally tolerated dose of DPPE (240 mg/m2) over 80 or 440 minutes, in conjunction with a single chemotherapy drug to which, in most cases, the patient's tumor was previously resistant. Concentrations of DPPE in blood and urine were determined by high-performance liquid chromatography (HPLC). RESULTS In vitro, micromolar concentrations of DPPE potentiated (fivefold to 10-fold) chemotherapy cytotoxicity to both drug-sensitive and -resistant cells, but did not inhibit the p-glycoprotein pump; in vivo, serum levels of DPPE were 3 to 5 mumol/L at the end of 80 minutes and 1 to 2 mumol/L after 440 minutes of infusion. Of 48 patients monitored for a minimum of four DPPE/chemotherapy treatment cycles, 16 (33%) progressed, 12 (25%) stabilized, 12 (25%) improved, and eight (17%) responded (one complete and seven partial remissions). Four of 11 subjects who did not respond to the 80-minute infusion regimen improved with the 440-minute infusion; one had a partial remission of melanoma. In more than 600 patient-treatments, bone marrow toxicity was negligible (mean absolute neutrophil count [ANC] > 2.0 x 10(9)/L). Acute CNS symptoms associated with DPPE infusions were of relatively short duration (1 to 4 hours); delayed toxicity attributable to DPPE consisted of mild nausea and/or fatigue (1 to 2 days). CONCLUSION Although preliminary, the results suggest that more structured trials should be performed to determine whether DPPE may increase the therapeutic index of certain chemotherapy drugs.