bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up.
Authors: Hoffman M A , Janson D , Rose E , Rai K R 
Published: February 2017

PURPOSE To analyze initial and long-term outcomes after treatment of patients with active hairy-cell leukemia (HCL) with a single cycle of cladribine (2-CdA). PATIENTS AND METHODS Forty-nine patients with active HCL were treated with 2-CdA by continuous intravenous infusion at 0.1 mg/kg/d for a total of 7 days at the Long Island Jewish Medical Center between September 1990 and August 1992. Here we report on all patients followed-up until April 1996. RESULTS At 3 months after treatment, complete response (CR) occurred in 37 patients (76%) and partial response (PR) occurred in 12 patients (24%), for an overall response rate of 100% (95% confidence interval, 94% to 100%). At a median follow-up of 55 months, the relapse-free survival is 80% and overall survival is 95%. Ten patients (20%) have relapsed. Of the 26 patients in whom lymphocyte phenotyping was performed, four were found to have a CD25-negative phenotype. All four of these patients had PRs only and all relapsed. Eight patients have been re-treated with 2-CdA, and all achieved at least a partial remission; two of these have already relapsed with remission durations of less than 1 year. Five second malignancies have occurred in four patients. CONCLUSION With a median follow-up of more than 4 years, 39 patients (80%) continue in remission. Only two deaths have occurred. A CD25-negative phenotype may predict for a poorer response to 2-CdA. Patients who relapse may be re-treated with 2-CdA, but subsequent remissions may be of shorter duration. There has not been a markedly increased incidence of second malignancies or late opportunistic infections.
Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL.
Authors: Heckman K D , Weiner G J , Davis C S , Strauss R G , Jones M P , Burns C P 
Published: February 2017

PURPOSE We designed and conducted a randomized single-institution trial comparing two common prophylactic platelet transfusion thresholds in patients undergoing induction therapy for acute leukemia. PATIENTS AND METHODS Seventy-eight patients undergoing induction therapy for acute leukemia were randomized to receive prophylactic apheresis platelet concentrates when the platelet count was either < or = 10,000/microL or < or = 20,000/microL. RESULTS There was no significant difference in the total number of bleeding episodes per patient with a median of four in the < or = 10,000/microL arm and two in the < or = 20,000/microL arm (25th to 75th percentiles of 2, 7 and 1, 5, respectively; P = .12). Patients randomized to the < or = 10,000/microL arm received more platelet transfusions for bleeding [one (0, 2) v zero (0, 0); P = .0003]. In contrast, patients on the < or = 20,000/microL arm received more platelet transfusions for prophylactic indications [10 (5, 14) v six (3, 8); P = 0.001], as would be expected, but less for bleeding. Nevertheless, the total number of platelet transfusions given to patients on the < or = 20,000/microL arm was higher and nearly significant [11 (6, 15) v seven (5, 11); P = .07]. There were no statistically significant differences between the groups with regard to RBC transfusion requirements, febrile days, days hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission rate, or death during induction chemotherapy. No patient in either group died from hemorrhage or underwent major surgery for bleeding complications. CONCLUSION Giving prophylactic platelets at a threshold of < or = 10,000/microL compared with < or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.
Orbital development in long-term survivors of retinoblastoma.
Authors: Kaste S C , Chen G , Fontanesi J , Crom D B , Pratt C B 
Published: February 2017

PURPOSE To determine the effects of enucleation, irradiation, and age at diagnosis on bony orbital growth in long-term survivors of retinoblastoma using measurements based on computed tomographic (CT) imaging. PATIENTS AND METHODS We used CT obtained at a median age of 13 years to measure orbital volume and configuration in 54 patients who had been treated for retinoblastoma a minimum of 5 years previously. RESULTS Enucleation and high-dose orbital irradiation (> 35 Gy) both independently adversely affected orbital development (P = .014 and P = .022, respectively). Orbital volume differences for children treated when < or = 1 year old were no greater than those for children treated when older than 1 year of age. In children treated for bilateral retinoblastoma, the impact of enucleation on orbital development was not statistically different from that of irradiation (P = .13). Small implants (12 to 14 mm in diameter) were more commonly associated with smaller orbital volumes. Migration of orbital implants was associated with the smaller orbital sphere size in children < or = 1 year of age (P < .035). CONCLUSION Treatment for retinoblastoma compromises orbital development. Resulting orbital asymmetry seems to be at least partially related to the size of the implant. Detailed imaging-based measurements of orbital volume and configuration may aid the planning for cosmetic and reconstructive surgery in those who develop orbital asymmetry.
Phase III controlled evaluation of sucralfate to alleviate stomatitis in patients receiving fluorouracil-based chemotherapy.
Authors: Loprinzi C L , Ghosh C , Camoriano J , Sloan J , Steen P D , Michalak J C , Schaefer P L , Novotny P J , Gerstner J B , White D F , Hatfield A K , Quella S K 
Published: February 2017

PURPOSE Stomatitis is a major dose-limiting toxicity of bolus fluorouracil (5FU)-based chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data that suggested a sucralfate oral solution could alleviate chemotherapy-induced oral mucositis, we developed a prospective trial to test this contention. PATIENTS AND METHODS A phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered onto the study at the time of the first cycle of 5FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5FU. In addition, each patient was randomized to receive either a sucralfate solution or a placebo solution to be used if they developed mouth tenderness or mouth sores. The study solution was to be used four times daily for 7 days starting on the first day of mouth tenderness or mouth sores. Stomatitis scores were determined by health care providers and by patients themselves. RESULTS There was a total of 131 assessable patients entered onto this trial, 50 of whom developed mucositis and used the study medication (27 sucralfate and 23 placebo). There was no suggestion of any difference in stomatitis severity or duration on either protocol arm. CONCLUSION The resultant data from this clinical trial did not support the prestudy hypothesis that sucralfate would be beneficial for the treatment of 5FU-induced stomatitis.
Decision analysis in locally advanced non-small-cell lung cancer: is it useful?
Authors: Brundage M D , Groome P A , Feldman-Stewart D , Davidson J R , Mackillop W J 
Published: February 2017

PURPOSE The optimal management of locally advanced non-small-cell lung cancer (NSCLC) has not been established. While combined-modality treatments have been shown to increase the survival of patients with this illness, the appropriate balance between the benefit of increased quantity of life and the quality-of-life costs of the more toxic treatment combinations remains unresolved. Decision analysis has been promoted as useful when medical decisions must be made under conditions of uncertainty. We consider the potential of this method to guide therapy in locally advanced NSCLC. METHODS We developed two types of decision models that addressed the choice between radiation alone and combined chemotherapy-radiation therapy in locally advanced NSCLC. The models were constructed using the principles of decision analysis. RESULTS The models successfully replicated results of relevant clinical trials published in the literature. The analyses of both models showed that the treatment decision was sensitive to patients' values, despite significant increases in survival rates. The models clarified a need for further validation of the three fundamental components: structuring the decision, determining the probabilities of events, and assigning utilities to treatment outcomes. CONCLUSION In the setting of NSCLC, the models suggest that quality-of-life considerations are important in the treatment choice. Further research is required to identify the health states critical to the decision, the probabilities for occurrence of these health states, and valid measures of their utility.
Paclitaxel and concurrent radiation for locally advanced pancreatic and gastric cancer: a phase I study.
Authors: Safran H , King T P , Choy H , Hesketh P J , Wolf B , Altenhein E , Sikov W , Rosmarin A , Akerley W , Radie-Keane K , Cicchetti G , Lopez F , Bland K , Wanebo H J 
Published: February 2017

PURPOSE To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and potential antitumor activity of weekly paclitaxel with concurrent radiation (RT) for locally advanced pancreatic and gastric cancer. PATIENTS AND METHODS Thirty-four patients with locally advanced adenocarcinoma of the pancreas or stomach were studied. The initial dose of paclitaxel was 30 mg/m2 by 3-hour intravenous (I.V.) infusion repeated every week for 6 weeks with 50 Gy RT. Doses were escalated at 10-mg/m2 increments in successive cohorts of three new patients until dose-limiting toxicity was observed. RESULTS The dose-limiting toxicities at 60 mg/m2/wk were abdominal pain within the RT field, nausea, and anorexia. Of 23 patients with assessable disease, 11 (seven with gastric, four with pancreatic cancer) had objective responses for an overall response rate of 48%. CONCLUSION Concurrent paclitaxel with upper abdominal RT is well tolerated at dosages that have substantial activity. A phase II trial of neoadjuvant paclitaxel and RT at the MTD of 50 mg/m2/wk is underway.
Fluorouracil plus racemic leucovorin versus fluorouracil combined with the pure l-isomer of leucovorin for the treatment of advanced colorectal cancer: a randomized phase III study.
Authors: Scheithauer W , Kornek G , Marczell A , Salem G , Karner J , Kovats E , Burger D , Greiner R , Pidlich J , Schneeweiss B , Raderer M , Rosen H , Depisch D 
Published: February 2017

PURPOSE To compare the efficacy and toxicity of fluorouracil (FU) and racemic leucovorin (d,l-LV) versus FU combined with the l-isomer of leucovorin (l-LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 248 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either FU (400 mg/m2/d by intravenous [I.V.] infusion for 2 hours) and racemic LV (100 mg/m2/d by I.V. bolus injection) given for 5 consecutive days, or the combination of FU and the pure l-isomer of LV using the same dose schedule. In both treatment arms, courses were administered every 28 days if toxicity allowed for a total of 6 months, unless evidence of tumor progression was documented earlier. RESULTS There were no significant differences between the FU/racemic LV and the FU/l-LV arm in the overall response rate (25% v 32%), duration of response (7.2 v 8.0 months), median time to progression or death (6.25 v 8.0 months), or median overall survival time (14.5 v 15.0 months). Except for minor myeloid toxic effects associated with FU/l-LV, there was also no significant difference in terms of adverse reactions. Gastrointestinal symptoms, specifically mucasitis and diarrhea, were less frequent and less severe in both treatment arms compared with other trials with FU/racemic LV reported in the literature, which might be because of the prolonged administration of FU used in both arms. CONCLUSION The combination of FU/l-LV produced response rates, response durations, and survival times similar to those with FU/d,l-LV. Biochemical modulation of FU by either pure l-LV or racemic LV thus appears to result in equivalent clinical efficacy.
Liver resection for colorectal metastases.
Authors: Fong Y , Cohen A M , Fortner J G , Enker W E , Turnbull A D , Coit D G , Marrero A M , Prasad M , Blumgart L H , Brennan M F 
Published: February 2017

PURPOSE More than 50,000 patients in the United States will present each year with liver metastases from colorectal cancers. The current study was performed to determine if liver resection for colorectal metastases is safe and effective and to evaluate predictors of outcome. MATERIALS AND METHODS Data for 456 consecutive resections performed between July 1985 and December 1991 in a tertiary referral center were analyzed. RESULTS The perioperative mortality rate was 2.8%, with a mortality rate of 4.6% for resections that involved a lobectomy or more. The median hospital stay was 12 days and only 9% of patients were admitted to the intensive care unit. The 5-year survival rate is 38%, with a median survival duration of 46 months. By univariate analysis, nodal status of the primary lesion, short disease-free interval before detection of liver metastases, carcinoembryonic antigen (CEA) level greater than 200 ng/mL, multiple liver tumors, extrahepatic disease, large tumors, or positive resection margin was predictive of poorer outcome. Sex, age greater than 70 years, site of primary tumor, or perioperative transfusion was not predictive of outcome. By multivariate analysis, positive margin, size greater than 10 cm, disease-free interval less than 12 months, multiple tumors, and extrahepatic disease were independent predictors of poorer outcome. Short disease-free interval or multiple tumors were nevertheless associated with a 5-year survival rate greater than 24%. CONCLUSION Liver resection for colorectal metastases is safe and effective therapy and currently represents the only potentially curative therapy for metastatic colorectal cancer. The only absolute contraindication to resection is extrahepatic disease. A randomized trial to examine efficacy of surgical resection cannot ethically be performed. Liver resection should be considered standard therapy for all fit patients with colorectal metastases isolated to the liver.
High-dose chemotherapy with hematopoietic rescue in patients with stage III to IV ovarian cancer: long-term results.
Authors: Legros M , Dauplat J , Fleury J , Cure H , Suzanne F , Chassagne J , Bay J O , Sol C , Canis M , Condat P , Choufi B , Tavernier F , Glenat C , Chollet P , Plagne R 
Published: February 2017

PURPOSE A series of 53 patients with poor-prognosis epithelial ovarian cancer treated with high-dose chemotherapy (HDC) followed by hematopoietic rescue was retrospectively studied from the day of diagnosis for toxicity and long-term survival analysis. PATIENTS AND METHODS Patients were treated with surgery followed by cisplatin combination chemotherapy. After second-look operation (SLO), HDC was administered: 23 patients received melphalan (140 mg/m2 on day 1) and 30 patients received a combination of carboplatin (400 mg/m2 on days 1 to 4) and cyclophosphamide (1.6 g/m2 on days 1 to 4). After HDC, autologous stem-cell transplantation was performed for hematologic support. RESULTS One patient died of cardiac failure after HDC, but the acute toxicity was acceptable for the other patients. With a median follow-up of 81.5 months, the 5-year overall survival rate for the 53 patients was 59.9% and the disease-free survival (DFS) rate at 5 years was 23.6%. Twenty-four patients (45.3%) were alive, 12 with no evidence of disease and 12 with recurrent disease. The best results were achieved in 19 patients with pathologic complete response at SLO (74.2% 5-year overall survival; 32.8% 5-year DFS). CONCLUSION HDC followed by autologous stem-cell support is a well-tolerated therapeutic approach for patients with poor-prognosis ovarian carcinoma. In this report, the 59.9% survival of 53 patients at 5 years must be compared to the 20% to 30% 5-year survival observed after conventional therapy. These results should be confirmed by an ongoing prospective randomized trial.
Treatment of brain metastases in patients with testicular cancer.
Authors: Bokemeyer C , Nowak P , Haupt A , Metzner B , Köhne H , Hartmann J T , Kanz L , Schmoll H J 
Published: February 2017

PURPOSE Despite improved cure rates for patients with metastatic testicular cancer with cisplatin-based combination chemotherapy, patients who develop brain metastases are generally considered to possess a poor prognosis. This report summarizes the long-term results in 44 patients with brain metastases from testicular cancer treated between 1978 and 1995 at Hannover University Medical School. PATIENTS AND METHODS Histologically, 42 patients (95%) had a nonseminomatous germ cell cancer and two patients (5%) a seminoma. Thirty-nine patients (89%) had lung metastases and 37 (84%) fulfilled the criteria for advanced disease according to the Indiana University classification even without considering the brain metastases. Eighteen patients (41%) presented with brain metastases at primary diagnosis (group 1), four (9%) developed brain metastases at relapse after a previous favorable response to combination chemotherapy (group 2), and 22 (50%) developed brain metastases during or directly after cisplatin-based chemotherapy. Chemotherapy consisted of cisplatin-based combination treatment and radiotherapy was given as whole-brain irradiation of 30 to 40 Gy and in single cases combined with a boost of 10 Gy to single lesions. RESULTS Overall, 10 patients achieved long-term survival (23%; 95% confidence interval [CI], 10.1% to 35.4%). The prognosis was significantly better for patients in groups 1 and 2, with six of 18 (33%) and three of four (75%) patients alive, compared with only one of 22 (5%) in group 3 (P < .01). Patients treated with either chemotherapy or radiotherapy alone did not achieve long-term survival, while nine of 28 (32%) who received treatment with both modalities with or without surgery achieved sustained long-term survival. During univariate analysis, patients with the diagnosis of brain metastases at first presentation (P < .01), patients with a single brain lesion (P < .02), and patients who received combined chemotherapy and radiotherapy (P < .03) had a significantly improved outcome. CONCLUSIONS Long-term survival can be achieved in approximately 25% of patients with brain metastases from testicular cancer by combined treatment with brain irradiation and aggressive cisplatin-based chemotherapy. Patients who develop brain metastases during systemic treatment should receive only palliative radiation therapy, since sustained survival will not be reached.
Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients.
Authors: Gupta E , Mick R , Ramirez J , Wang X , Lestingi T M , Vokes E E , Ratain M J 
Published: February 2017

PURPOSE We conducted a pharmacokinetic and pharmacodynamic evaluation of irinotecan (CPT-11) and determined the effect of race and sex on disposition and toxicity of CPT-11. We tested the efficacy of acetaminophen (AAP) to phenotype SN-38 glucuronidation. PATIENTS AND METHODS Forty patients received a dose of 145 mg/m2 of CPT-11 as a 90-minute infusion. Total CPT-11, SN-38, and SN-38G were quantitated in plasma and urine samples. Following administration of 1 g AAP, urinary concentrations of AAP and AAP-glucuronide (AAP-G) were assessed. RESULTS CPT-11 exhibited a mean elimination half-life (t1/2) of 8.8 hours, an average clearance (CL) of 14.6 L/h/m2, and a mean volume of distribution at steady-state (Vdss) of 136 L/m2. SN-38 and SN-38G had low plasma availabilities (3% and 10% relative to CPT-11), with mean t1/2 values of 11.6 and 10.5 hours, respectively. Urinary recovery accounted for 15% of the dose. Race and sex had no effect on the plasma availability of CPT-11, SN-38, and SN-38G. The applicability of biliary index (BI) in predicting dose-limiting intestinal toxicity was validated. Patients who developed grade 3 or 4 toxicity had significantly higher index values compared with patients with grade 0 to 2 toxicity (P = .001). There was no difference in the incidence and severity of toxicity based on race and sex. AAP was a poor predictor of SN-38 glucuronidation. CONCLUSION The high degree of interpatient variability in parameter estimates suggests pharmacogenetic variation or differential induction or inhibition of the sequential metabolic pathway of CPT-11, as well as variability in transport systems. The low urinary recovery indicates substantial biliary excretion and supports the significant correlation between intestinal toxicity and BI. Black patients are not at increased risk of toxicity. An assessment of individual differences in SN-38 conjugation remains to be established.
High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: a phase I trial.
Authors: Tempero M , Leichner P , Dalrymple G , Harrison K , Augustine S , Schlam J , Anderson J , Wisecarver J , Colcher D 
Published: February 2017

PURPOSE A phase I trial that evaluated for extrahematopoietic toxicity was conducted with iodine-131 (131I) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA). PATIENTS AND METHODS After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two to three per activity level) underwent a single treatment with 131I-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. RESULTS No dose-limiting extrahematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The T1/2 for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7 +/- 10.4 and 46.1 +/- 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. CONCLUSION Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of 131I-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy beta emissions, such as yttrium 90, and on strategies to optimize access of antibody to target antigens.