bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter phase II trial of interleukin-2, interferon-alpha, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma.
Authors: Stadler W M , Kuzel T , Dumas M , Vogelzang N J 
Published: February 2017

PURPOSE To determine the response rate and toxicity of oral 13-cis-retinoic acid (CRA) added to an outpatient regimen of subcutaneous interleukin-2 (IL2) and interferon-alpha (IFNA) in previously untreated patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS Eligibility included a performance status of 2 or better, no significant end-organ dysfunction, and written informed consent. Characteristics of 47 of 48 assessable patients included a median performance status of 0, prior nephrectomy in 68% of patients, one metastatic site in 30% of patients, and lung-only metastatic disease in 21% of patients. Therapy consisted of IL2 11 x 10(6) IU 4 days per week for 4 weeks, IFNA 9 x 10(6) IU 2 days per week for 4 weeks, and CRA 1 mg/kg daily on a 6-week cycle. RESULTS Eight of 47 patients (17%) responded (one complete response, seven partial responses). Three partial responders were rendered disease free by subsequent surgical resection. Four additional patients experienced a minor response in lung or soft tissue metastases. The median duration of response, which included minor responses, was 42 weeks, and median survival was 74 weeks (17 months). Grades 3 or greater toxicities during the first cycle included flu-like symptoms (21% of patients), fatigue (6% of patients), and nausea and vomiting (15% of patients). Significant cumulative toxicities were hyperlipidemia (four of 18 patients), and cardiomyopathy (one of 18 patients). There was one therapy-related death. CONCLUSION Outpatient CRA plus IL2 and IFNA is feasible and modestly effective in metastatic RCC. The prolonged median survival is encouraging, but randomized trials are required to show that the combination represents an improvement over single-agent immunotherapy.
Ninety-six-hour infusional paclitaxel as salvage therapy of ovarian cancer patients previously failing treatment with 3-hour or 24-hour paclitaxel infusion regimens.
Authors: Markman M , Rose P G , Jones E , Horowitz I R , Kennedy A , Webster K , Belinson J , Fusco N , Fluellen L , Kulp B , Peterson G , McGuire W P 
Published: February 2017

PURPOSE To test the hypothesis that prolonged infusion of paclitaxel (96 hours) might overcome resistance to shorter infusion schedules (3 or 24 hours) in ovarian cancer. PATIENTS AND METHODS A total of 30 patients with advanced ovarian cancer (24 patients), primary carcinoma of the peritoneum (four patients), or fallopian tube cancer (two patients) who previously had received paclitaxel administered on either a 3-hour or 24-hour schedule were treated with the agent delivered as a 96-hour infusion (30 to 35 mg/m2/d x 4 days) on an every 3-week program. RESULTS Although the regimen generally was well tolerated, no objective responses were observed. CONCLUSION In patients with ovarian cancer who have shown resistance to shorter paclitaxel infusion schedules, ninety-six hour infusional paclitaxel is an inactive treatment strategy. This makes it less likely that protracted infusion of paclitaxel will improve outcome when used as part of primary therapy of ovarian cancer. An ongoing randomized study will answer that question.
Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?
Authors: Leblond V , Davi F , Charlotte F , Dorent R , Bitker M O , Sutton L , Gandjbakhch I , Binet J L , Raphael M 
Published: February 2017

PURPOSE Organ recipients are at a high risk of posttransplant lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy. Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV. PATIENTS AND METHODS There were seven kidney, three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outcome were compared with those in 21 patients with EBV-associated PTLD treated in our institution (group II). EBV was detected with at least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1 (LMP1) expression by immunohistochemistry. RESULTS The time between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean, 546; median, 180), and was significantly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in group I and nine in group II. The survival time was significantly longer in group II (P < .01). CONCLUSION EBV-negative PTLD may be a late serious complication of organ transplantation. Half the tumors observed after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.
Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma.
Authors: Taylor B V , Buckner J C , Cascino T L , O'Fallon J R , Schaefer P L , Dinapoli R P , Schomberg P 
Published: February 2017

PURPOSE The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials. METHODS We studied 701 high-grade brain tumor patients entered onto two consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and physical function over time. Patients who did not demonstrate tumor progression within 60 days of the assessment time were considered nonprogressors at that evaluation. A loss of greater than 3 points on the MMSE was considered significant deterioration. RESULTS The number of patients who experienced a greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54 nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30 nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22 nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times overlapped, which indicates no statistically significant increase in the percentage of patients who experienced a significant decrease in their MMSE score. Patients who demonstrated a significant decrease in their MMSE score were significantly older than those who did not (P = .0017) at 6 months and remained so throughout follow-up; moreover, they had a significantly shorter time to progression and death. ECOG PS was strongly negatively correlated with MMSE score throughout the study, and MMSE score at all time intervals was correlated with baseline PS. CONCLUSION In this population of glioma patients who received radiotherapy, there is no clear trend to cognitive worsening. Factors such as older age, poorer PS, and subclinical tumor progression may be more significant factors in those patients who did demonstrate a significant cognitive decline.
Cellular pharmacodynamics and plasma pharmacokinetics of parenterally infused hydroxyurea during a phase I clinical trial in chronic myelogenous leukemia.
Authors: Gandhi V , Plunkett W , Kantarjian H , Talpaz M , Robertson L E , O'Brien S 
Published: February 2017

PURPOSE To determine the maximum-tolerated dose (MTD), toxicities, and antileukemic activity of hydroxyurea (HU) administered intravenously to patients with advanced-phase chronic myelogenous leukemia (CML). Further objectives were to analyze pharmacodynamic effect on deoxynucleotides (dNTPs) and to seek relationships between the decrease in dNTP pools and inhibition of DNA synthesis in CML blasts. PATIENTS AND METHODS HU (8, 12, 18, 27, and 40 g/m2) was administered intravenously by a 24-hour continuous infusion to 19 adults with CML in blastic or accelerated phase. Plasma levels of HU were analyzed in all patients. To determine the role of HU in inhibiting ribonucleotide reductase, dNTP pools in the leukemia cells were quantitated. Correlations were sought with these parameters and DNA synthesis inhibition measured ex vivo by [3H]thymidine incorporation. RESULTS The MTD of HU given as a 24-hour infusion was 27 g/m2. The dose-limiting toxicity was mucositis. There was a significant but transient myelosuppression, with nadir counts generally seen 3 to 4 days after the dose. The steady-state concentration of HU in plasma was achieved by 6 hours, and was proportional to the dose. There was a median 57% decrease in the deoxyadenosine triphosphate (dATP) pool in circulating blasts. In contrast, deoxyguanosine triphosphate (dGTP) and pyrimidine dNTPs were not significantly affected. The extent of DNA synthesis inhibition was related to the residual concentrations of intracellular dATP. CONCLUSION A 24-hour infusion of HU results in significant but transient myelosuppression in advanced-phase CML. The specific decrease of intracellular dATP correlated with the inhibition of DNA synthesis in CML blasts. This pharmacodynamic action of HU provides a rationale for combination with other chemotherapeutic agents, the effects of which could be augmented by the decline in dATP pools.
Radiation therapy for rectosigmoid and rectal cancer: results of the 1992-1994 Patterns of Care process survey.
Authors: Minsky B D , Coia L , Haller D G , Hoffman J , John M , Landry J , Pisansky T M , Willett C , Mahon I , Owen J , Berkey B , Katz A , Hanks G 
Published: February 2017

PURPOSE To determine the US national practice standards for patients with adenocarcinoma of the rectum treated in radiation oncology facilities. MATERIALS AND METHODS A national survey of 57 institutions identified 507 eligible patients who received radiation therapy as a component of their treatment for rectal cancer. A stratified two-stage cluster sampling with simple random sampling at each stage for each stratum was used and on-site surveys were performed. RESULTS Of the 507 patients, 378 (75%) received postoperative therapy, 110 (22%) received preoperative therapy, 17 (2%) received both preoperative and postoperative therapy, and less than 0.5% received intraoperative radiation alone. To more accurately assess the utilization of modern radiation techniques as well as recommendations of the National Cancer Institute (NCI)-sponsored, randomized, postoperative, adjuvant combined modality therapy rectal cancer trials into current practice, the analysis was limited to the 243 (48%) patients with tumor, node, and metastasis staging system classification T3 and/or N1-2M0 disease who underwent conventional surgery with negative margins. Although only 7% were treated on a clinical trial, 90% received chemotherapy for a median of 21 weeks. Most were treated with modern radiation treatment techniques. In contrast, techniques to identify and help exclude the small bowel from the radiation field were not routinely used. CONCLUSION Despite the fact that only 7% of patients with T3 and/or N1-2M0 disease were treated on a clinical trial, such trials appear to have resulted in a positive influence on the standard of practice within the oncology community. Although there are still some deficiencies, the majority of these patients received combined modality therapy and were treated with modern radiation therapy techniques.
Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.
Authors: Fisher B , Bryant J , Wolmark N , Mamounas E , Brown A , Fisher E R , Wickerham D L , Begovic M , DeCillis A , Robidoux A , Margolese R G , Cruz A B , Hoehn J L , Lees A W , Dimitrov N V , Bear H D 
Published: February 2017

PURPOSE To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.
Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation--results of a retrospective analysis on 120 patients autografted in a single institution.
Authors: Fouillard L , Laporte J P , Labopin M , Lesage S , Isnard F , Douay L , Lopez M , Aoudjhane M , Zunic P , Cheron N , Stachowiak J , Lemonnier M P , Andreu G , Belkacemi Y , Noël-Walter M P , Morel P , Fenaux P , Jouet J P , Bauters F , Najman A , Gorin N C 
Published: February 2017

PURPOSE To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution. PATIENTS AND METHODS A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement. RESULTS Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS. CONCLUSION This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.
Phase II trial of nitrogen mustard, vincristine, and procarbazine in patients with recurrent glioma: North Central Cancer Treatment Group results.
Authors: Galanis E , Buckner J C , Burch P A , Schaefer P L , Dinapoli R P , Novotny P J , Scheithauer B W , Rowland K M , Vukov A M , Mailliard J A , Morton R F 
Published: February 2017

PURPOSE Previous investigators have reported responses in 52% of patients treated with mechlorethamine (nitrogen mustard), vincristine, and procarbazine (MOP) for recurrent glioma. To confirm these promising results, we conducted a phase II prospective study. PATIENTS AND METHODS Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen. Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2, respectively, intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8, and procarbazine 100 mg/m2 orally on days 1 to 14. Cycles were repeated every 28 days. RESULTS Of 61 patients assessable for response, eight responded (13%), with one complete response (CR). Responses were as follows: low-grade gliomas, 19%; anaplastic astrocytomas, 11%; anaplastic oligodendrogliomas or oligoastrocytomas, 25%; and glioblastomas, 4.3%. The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23% and platelet nadirs less than 25,000/microL in 13% of patients. Two patients died of infection in the setting of neutropenia. Nonhematologic toxicity included neurosensory changes in 21% of patients (severe in 3%) and severe dermatologic reactions in 8%. In multivariate analysis, Eastern Cooperative Oncology group (ECOG) performance status (PS) was the best predictor for response to chemotherapy (P=.01) and time to progression (P=.008), while PS and grade were the most important predictors of survival (P=.002 and .05, respectively). CONCLUSION This study did not confirm the high response rate previously reported in recurrent gliomas. Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low-grade gliomas had the highest response rates (25% and 19%, respectively). In multivariate analysis, ECOG PS was the best predictor of response, while PS and tumor grade were the most important predictors of survival.
Phase I and pharmacologic study of estramustine phosphate and short infusions of paclitaxel in women with solid tumors.
Authors: Garcia A A , Keren-Rosenberg S , Parimoo D , Rogers M , Jeffers S , Koda R , Muggia F M 
Published: February 2017

PURPOSE We sought to determine the tolerance of estramustine phosphate (EMP) combined with a 3-hour paclitaxel infusion in women with solid paclitaxel-pretreated solid tumors. Paclitaxel pharmacology was to be studied at the recommended phase II dose. PATIENTS AND METHODS Paclitaxel was administered to cohorts of at least three assessable patients at doses of 150, 180, 210, and 225 mg/m2, while EMP was given at 900 and 1,200 mg/m2/d in divided doses orally for 2 days preceding and on the day of paclitaxel. The pharmacologic study was performed at 225 mg/m2 paclitaxel given in the absence and 3 weeks later in the presence of EMP 900 mg/m2/d. RESULTS Thirty-eight patients received a total of 178 courses. Grade 3 nausea, vomiting, and diarrhea were common at EMP 1,200 mg/m2 and paclitaxel 225 mg/ m2; this was considered the maximum-tolerated dose. Since these toxicities appeared related to EMP, the pharmacologic study used a dose of 900 mg/m2 of this agent with 225 mg/m2 paclitaxel. Antitumor activity was documented against breast and ovarian cancers at all levels. Paclitaxel pharmacokinetics without and with EMP did not differ. CONCLUSION EMP 900 mg/m2 for 3 days and 225 mg/m2 paclitaxel by 3-hour infusion are well tolerated; antitumor activity was seen in women with paclitaxel-pretreated solid tumors. This apparent enhancement of antitumor effects is unlikely to be mediated by P-glycoprotein.
Patterns of Outcome Following Recurrence After Myeloablative Therapy With Autologous Bone Marrow Transplantation for Follicular Lymphoma
Authors: Apostolidis J. , Foran J. M. , Johnson P.W.M. , Norton A. , Amess J. , Matthews J. , Bradburn M. , Lister T.A. , Rohatiner A. Z.S. 
Published: February 2017

PURPOSE: To assess the patterns of recurrence, management, and survival following recurrence after myeloablative therapy with autologous bone marrow transplantation (ABMT) in patients with follicular lymphoma (FL). PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with FL received cyclophosphamide and total-body irradiation with ABMT as consolidation of second or subsequent remission. RESULTS: Median length of follow-up was 5½ years, and 33 patients developed recurrent lymphoma a median of 14 months after ABMT. In 26 patients, the recurrence was overt; in seven, it was detected on surveillance investigation. Twenty-six patients presented with recurrence at previous sites of disease. Twenty-two patients (67%) had FL at the time of recurrence; in 11 (33%), there was evidence of transformation to diffuse large B-cell lymphoma. Eight patients were managed expectantly; five were alive 21 to 53 months later. Twenty-five patients have required treatment to date; eight remained alive 6 months to 10 years later, and five were in remission. The Kaplan-Meier estimate of patients alive 5 years after recurrence is 45% (95% confidence interval, 27% to 62%). In univariate and multivariate analyses, survival after recurrence and overall survival after diagnosis were similar to those of a historical control group who received conventional treatment, before the introduction of myeloablative therapy (adjusted hazard ratio [HR], 1.56, P = .3, and HR, 1.34, P = .4, respectively). CONCLUSION: The survival pattern of patients with FL following recurrence after myeloablative therapy and ABMT suggests that this treatment does not compromise outcome in patients in whom it fails, reflecting the survival pattern of the disease when treated conventionally.