bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of relapse in childhood acute lymphoblastic leukemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. Nordic Society for Pediatric Hematology and Oncology.
Authors: Schmiegelow K , Schrøder H , Gustafsson G , Kristinsson J , Glomstein A , Salmi T , Wranne L 
Published: February 2017

PURPOSE During maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), the cytotoxic metabolites of methotrexate (MTX polyglutamates) and mercaptopurine (6MP) (thioguanine nucleotides [6TGN]) accumulate intracellularly, including in erythrocytes (E-MTX and E-6TGN) with large interindividual variations. In the present Nordic Society for Pediatric Hematology and Oncology (NOPHO) study, the relation of E-MTX and E-6TGN to relapse risk was explored. PATIENTS AND METHODS Two hundred ninety-seven patients with non-B-cell ALL, aged 1 to 14 years, on oral MTX and 6MP had E-MTX and E-6TGN levels measured three to 35 (median, eight) and three to 75 (median, nine) times, respectively. For each patient, a mean of all E-MTX (mE-MTX) and E-6TGN (mE-6TGN) measurements was calculated, as well as the product of mE-MTX and mE-6TGN (mE-MTX-6TGN), since MTX and 6MP may have synergistic action. RESULTS For patients in remission, the median mE-MTX and mE-6TGN values were 4.7 nmol/mmol hemoglobin (Hgb) (range, 0.4 to 10.3) and 173 nmol/mmol Hgb (range, 58 to 846). With a median follow-up duration of 66 months for patients in remission, 64 patients relapsed. Cox regression analysis identified mE-MTX-6TGN and sex to be the most significant parameters to predict relapse (global P = .001). Factors that predicted a better prognosis were high mE-MTX 6TGN and female sex. Patients who had a mE-MTX-6TGN less than the product of the median mE-MTX and median mE-6TGN (813 [nmol/mmol Hgb]2) had a significantly poorer event-free survival (EFS) than did patients with higher values (5-year probability of EFS [pEFS5y], 0.70 v 0.86; P = .001). CONCLUSION The pharmacokinetics of MTX and 6MP may have significant influence on the risk of relapse. The value of dose adjustments by E-MTX and E-6TGN remains to be determined.
Phase II study of paclitaxel in relapsed non-Hodgkin's lymphomas.
Authors: Wilson W H , Chabner B A , Bryant G , Bates S , Fojo A , Regis J , Jaffe E S , Steinberg S M , Goldspiel B R , Cheson B D 
Published: February 2017

PURPOSE To assess the efficacy and toxicity of paclitaxel administered as a 96-hour infusion to patients with relapsed non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS Eligible patients had relapsed NHL and measurable disease and were considered incurable. Paclitaxel was infused at a dose of 140 mg/m2 every 3 weeks. Premedications to prevent paclitaxel hypersensitivity reactions were not administered and no patients received corticosteroids. Expression of the multidrug resistance (mdr-1) gene was determined in tumor from 17 patients by mRNA quantitative polymerase chain reaction (PCR). RESULTS Thirty-one patients received a total of 99 cycles of paclitaxel. Two patients were not assessable for response. The median age was 50 years, 71% had stage IV disease, and intermediate/high-grade histology was present in 65% of patients. Patients had received a median of three prior chemotherapy regimens, and 68% of patients had responded to the previous chemotherapy (chemotherapy-sensitive). Of 29 assessable patients, five (17%) achieved a partial response (PR). With a median potential follow-up time of 17 months, the median event-free and overall survival durations were 1.6 and 7.5 months, respectively. No correlation was found between response to paclitaxel and extent of prior treatment or response. The mdr-1 gene was easily detectable in 14 of 17 tumor biopsies, but was low in all but one sample. The most serious toxicity was grade 4 neutropenia, which occurred during 14% of cycles. CONCLUSION Paclitaxel was well tolerated, but had a low response rate in patients with relapsed NHLs. There was no clear association between response to paclitaxel and extent of our response to prior treatment. Most patients had chemotherapy-sensitive disease, which suggests that the low response rate to paclitaxel was probably not due to general chemotherapy resistance. Paclitaxel provided good palliation in a minority of patients and is a reasonable agent to consider for use in patients who have failed to respond to standard chemotherapy.
Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrow transplantation.
Authors: Colwill R , Crump M , Couture F , Danish R , Stewart A K , Sutton D M , Scott J G , Sutcliffe S B , Brandwein J M , Keating A 
Published: February 2017

PURPOSE To evaluate the efficacy of carmustine (BCNU), etoposide, cytarabine (Ara-C), and melphalan (mini-BEAM) as salvage therapy in patients with relapsed or refractory Hodgkin's disease who were potentially eligible to undergo intensive therapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS Forty-four patients with refractory or relapsed Hodgkin's disease after front-line combination chemotherapy referred for consideration of ABMT were treated with mini-BEAM (BCNU 60 mg/m2 on day 1, etoposide 75 mg/m2 on days 2 to 5, Ara-C 100 mg/m2 twice per day on days 2 to 5, and melphalan 30 mg/m2 on day 6) to maximum response. Eleven patients were refractory to primary chemotherapy. Twenty-three patients were treated in first relapse and 10 in second or subsequent relapse; 21 received mini-BEAM as their first salvage regimen. Patients were restaged to determine disease status immediately before intensive therapy and transplant. RESULTS The overall response rate was 84% (exact 95% confidence interval [CI], 70% to 92%), with a complete response (CR) rate of 32% (95% CI, 20% to 47%) and a partial response (PR) rate of 52%. No treatment-related deaths were observed. Myelosuppression was the major toxicity. Almost all patients required platelet transfusions. Eighty-four percent were given RBC transfusions, and 54% required intravenous antibiotics for fever while neutropenic. CONCLUSION Mini-BEAM is a safe and effective regimen for treatment of refractory or relapsed Hodgkin's disease. Further studies are required to determine if responding patients have improved disease-free survival (DFS) after intensive therapy and ABMT.
Phase I trial of escalating doses of interleukin-1 beta in combination with a fixed dose of interleukin-2.
Authors: Triozzi P L , Kim J A , Martin E W , Young D C , Benzies T , Villasmil P M 
Published: February 2017

PURPOSE Interleukin-1 (IL-1) and IL-2 have synergistic antitumor and myelostimulatory activities. We investigated the clinical and biologic effects of IL-1/IL-2 therapy. PATIENTS AND METHODS Twenty patients with metastatic cancer, divided into five cohorts, were treated with escalating doses of IL-1 beta (0.005 to 0.2 micrograms/kg/d) administered as a 30-minute intravenous (IV) infusion on days 1 to 4, combined with a fixed dose of IL-2 (0.1 mg/m2/d) administered by continuous IV infusion on days 1 to 4. The 4-day cycles were repeated weekly for up to 8 weeks in the absence of toxicity and/or progressive disease. RESULTS Patients tolerated up to 0.2 microgram/kg/d of IL-1 beta in combination with IL-2 without severe adverse effects. Peripheral-blood CD4-to-CD8 ratios and lymphokine-activated killer (LAK) activity were higher at the lower doses (0.005 to 0.05 microgram/kg/d) of IL-1 beta and higher than that of a cohort of patients treated with IL-2 alone. WBC counts, primarily neutrophils, increased significantly with higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d). Platelet counts were not significantly altered. Increases in serum IL-6, interferon gamma (IFN-gamma), and soluble IL-2 receptor levels were observed, but did not vary with IL-1 beta dose. Tumor regressions were observed in patients with colorectal cancer, melanoma, and renal cell carcinoma. CONCLUSION IL-1 beta cancer be administered in combination with IL-2 with acceptable toxicity. Our results suggest that the addition of even low-dose IL-1 beta to IL-2 may be associated with potentially beneficial biologic activity; higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d) may add potentially beneficial hematologic activity.
The practice guidelines development cycle: a conceptual tool for practice guidelines development and implementation.
Authors: Browman G P , Levine M N , Mohide E A , Hayward R S , Pritchard K I , Gafni A , Laupacis A 
Published: February 2017

PURPOSE To develop a conceptual tool for the systematic development of cancer treatment practice guidelines. MATERIALS AND METHODS The guidelines development tool, the Practice Guidelines Development Cycle, was derived from observing an evidence-based practice guidelines initiative at a comprehensive cancer center in Ontario, Canada, and from a literature review that uncovered barriers to guidelines development and implementation. Based on the literature findings and direct observations of how clinicians struggled with evidence-based guidelines development, we evolved a framework to incorporate clinical and administrative factors (eg, costs) into evidence-based guidelines. Use of the Practice Guidelines Development Cycle is illustrated with a clinical example (the use of adjuvant systemic therapy in good-risk, node-negative premenopausal breast cancer patients). RESULTS The result is the Practice Guidelines Development Cycle, which consists of eight sequential steps, from topic selection to policy formulation. Independent validation of guidelines is included. The cycle products are the evidence-based recommendation, the practice guideline, and the practice policy. The main features of the cycle are emphasis on scientific evidence, acknowledgment of the roles of clinical experience and nonclinical (administrative) factors through consensus, and explicit separation of clinical and cost considerations in guidelines development. Twenty guidelines are currently in development. CONCLUSION Attention to the barriers of guidelines development and the sociocultural nature of clinical practice, and respect for clinical experience, can lead to improved strategies for guidelines development.
Collection of peripheral-blood diploid cells from chronic myelogenous leukemia patients early in the recovery phase from myelosuppression induced by intensive-dose chemotherapy.
Authors: Kantarjian H M , Talpaz M , Hester J , Feldman E , Korbling M , Liang J , Rios M B , Smith T L , Calvert L , Deisseroth A B 
Published: February 2017

PURPOSE To evaluate whether intensive chemotherapy followed by peripheral stem-cell (PSC) collections during early hematopoietic recovery results in a higher percentage of diploid cell collections in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). PATIENTS AND METHODS Fifty-five adults with Ph-positive CML received intensive chemotherapy with daunorubicin and high-dose cytarabine (ara-C) (DAUNO-HDAC; 26 patients) or fludarabine, high-dose ara-C, and mitoxantrone (FAM; 29 patients). Collections of the peripheral mononuclear cells were initiated when the WBC count was > or = 0.8 x 10(3)/microL. Simultaneous peripheral and marrow samples were subjected to cytogenetic studies. RESULTS Thirty-eight of 55 patients (69%) were able to undergo the PSC collections. The rate of collection was higher in chronic phase (26 of 30 patients; 87%) than in accelerated (11 of 17; 65%) and blastic phases (1 of 8; 12%). Among the 30 patients in chronic phase, cytogenetic analyses of PSC showed cytogenetic responses (Ph-positive < 95%) in 60%, which were major (Ph < 35%) in 43% and complete (Ph = 0%) in 27%. Seven of 19 patients with simultaneous studies (37%; 23% of total) had a significantly lower percentage of Ph-positive cells in the peripheral collection compared with the marrow collection; one had the reverse phenomenon (5%; 3% of total). Cytogenetic responses were modest in both peripheral and marrow collections in CML accelerated and blastic phases. Myelosuppression-associated complications were frequent, resulting in febrile episodes in 76% of patients. CONCLUSION PSC collection during early hematopoietic recovery from intensive chemotherapy allowed the collection of diploid-rich stem cells, mostly in chronic-phase CML. The approach could be used for in vivo purging before autologous stem-cell transplantation (ASCT).
Treatment outcome and prognostic factors for primary nasal lymphoma.
Authors: Liang R , Todd D , Chan T K , Chiu E , Lie A , Kwong Y L , Choy D , Ho F C 
Published: February 2017

PURPOSE To report our experience managing a large series of Chinese patients with primary nasal lymphoma. PATIENTS AND METHODS From January 1975 to December 1993, 100 patients (median age, 50 years) with newly diagnosed primary nasal lymphoma were studied. There were four low-grade, 62 intermediate-grade, nine high-grade, and 25 unclassifiable lymphomas. Immunophenotyping was performed in 45 patients: eight B cell, 35 T cell, and two uncertain. All cases of angiocentric lymphoma that were typed were T cell. Fifty-two patients had stage I disease, 15 had stage II, four had stage III, and 29 had stage IV. Only 15 patients had B symptoms (weight loss, night sweats, and/or fever), and 11 had bulky disease. Thirty-nine patients with clinically localized stage I and II disease received local radiotherapy alone (before 1980), and the remaining 28 stage I and II patients received combination chemotherapy followed by local radiotherapy. The 33 patients with advanced stage III and IV disease were given combination chemotherapy, and additional radiotherapy was given to five of them who had bulky local disease. RESULTS Significantly higher complete remission rates were observed in patients with early stages of disease and those without B symptoms. Superior disease-free survival after complete remission was observed in patients with stage I/II disease. Univariate factors associated with a better overall survival included age less than 60 years, stage I disease, and absence of B symptoms. Survival was significantly better in the subgroup of patients with stage I disease. CONCLUSION Patients with nasal lymphoma, especially those with advanced disease, seemed to have a poor prognosis, and their clinical outcome was not improved significantly by the use of chemotherapy instead of radiotherapy or the use of doxorubicin-containing chemotherapeutic regimens.
Impact of doxorubicin on survival in advanced ovarian cancer.
Authors: A'Hern R P , Gore M E 
Published: February 2017

PURPOSE Our study examined the impact of the addition of doxorubicin to ovarian cancer regimens in general, while removing the confounding influence of other drugs. MATERIALS AND METHODS We performed an overview using the data from two large analyses, the Advanced Ovarian Cancer Trialists Group (AOCTG [Br Med J 303:884-893, 1991] and Williams et al [Seminars in Oncol 19:120-128, 1992 (suppl 2)]) and the Ovarian Cancer Meta-Analysis Project (OCMP [J Clin Oncol 9:1668-1674, 1991]). RESULTS Our data suggest that the addition of doxorubicin significantly improves survival (hazards ratio, 0.85; 95% confidence interval [CI], 0.76 to 0.95; P = .003) and that the size of this benefit is of a similar magnitude to that of platinum. CONCLUSION The implication of our results is that the basic drugs for the standard treatment of advanced ovarian should be a combination of platinum and doxorubicin. The addition of an alkylating agent may add toxicity and lead to a dose reduction of these two drugs. In view of recent data on combination therapy with paclitaxel and platinum, it would be appropriate to compare this regimen with a combination of doxorubicin and platinum.
Thyroid function test changes with adjuvant tamoxifen therapy in postmenopausal women with breast cancer.
Authors: Mamby C C , Love R R , Lee K E 
Published: February 2017

PURPOSE While tamoxifen has been shown to alter concentration of many hormones and their binding globulins, there have been conflicting results regarding its effects on thyroid function tests. We sought to clarify these effects by studying subjects in a controlled clinical trial. PATIENTS AND METHODS We evaluated a subset of postmenopausal women who had participated in a longitudinal, double-blind, randomized, placebo-controlled toxicity study of tamoxifen 10 mg orally, twice daily. There were 14 subjects in both the tamoxifen and placebo groups. Measurement of thyroid-binding globulin (TBG), thyroxine uptake (T-Uptake), thyroxine (T4), and thyroid-stimulating hormone (TSH), and an indirect estimate of the free T4 index (FTI), were made for each subject before and after 3 months of treatment. RESULTS For T-Uptake, T4, and TBG, there were significant increases in the mean change from baseline to 3 months in the tamoxifen group compared with the placebo group (P = .02, .0001, and .003, respectively), while there were no significant changes in the measured TSH and in the calculated FTI. CONCLUSION We conclude that tamoxifen therapy in postmenopausal women results in increased TBG, with secondary increases in measured T-Uptake and T4 following. However, TSH and FTI levels are unchanged, and treated women remain eumetabolic.
Etoposide and carboplatin in extraocular retinoblastoma: a study by the Société Française d'Oncologie Pédiatrique.
Authors: Doz F , Neuenschwander S , Plantaz D , Courbon B , Gentet J C , Bouffet E , Mosseri V , Vannier J P , Mechinaud F , Desjardins L 
Published: February 2017

PURPOSE A phase II study of etoposide (VP-16) and carboplatin was performed in patients with extraocular retinoblastoma to evaluate the response rate with this drug combination. PATIENTS AND METHODS Twenty patients with extraocular retinoblastoma, age 9 to 120 months, were included in a cooperative multicenter phase II study of the Société Francçaise d'Oncologie Pédiatrique (SFOP). The schedule consisted of consecutive 5-day treatment with VP-16 100 mg/m2/d and carboplatin 160 mg/m2/d. RESULTS The response rate for the 20 patients was 85%; there were nine complete responses and eight partial responses. Hematologic toxicity was the only serious observed toxicity and was always manageable. CONCLUSION This combination of VP-16 and carboplatin is highly effective in extraocular retinoblastoma. The high response rate is encouraging for further evaluation of this drug combination in adjuvant chemotherapy when necessary after enucleation or in neoadjuvant chemotherapy for intraocular tumors.
Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma.
Authors: Bleehen N M , Newlands E S , Lee S M , Thatcher N , Selby P , Calvert A H , Rustin G J , Brampton M , Stevens M F 
Published: February 2017

PURPOSE Sixty patients with metastatic melanoma were treated in a phase II study with the imidazotetrazine derivative temozolamide to assess further the efficacy demonstrated in previous phase I studies. PATIENTS AND METHODS Fifty-five of 56 eligible patients were assessable for toxicity and 49 for response. The patients received temozolomide 150 mg/m2/d over 5 successive days orally (total dose, 750 mg/m2) in the first course. Courses were repeated every 4 weeks and the dose was escalated to 200 mg/m2/d x 5 (total dose, 1 g/m2) after the first course if toxicity was acceptable. Patients were all chemotherapy-naive, except for two who had previously received interferon alfa and one who had received interleukin-2 (the latter patient had also received two phase I drugs some time previously). RESULTS A complete response (CR) was documented in three patients (all with lung metastases) and a partial response (PR) in nine patients (21% CR plus PR rate). Seven of 56 patients were not assessable for response because of early death or deterioration. The overall response rate excluding these patients is 12 of 49 (24%). The median response duration was 6 months (range, 2.5 to 22+). Toxicity of the regimen, which was mainly hematopoietic, was low. The median survival duration for all patients was 5.5 months (range, 0.5 to 29.5). For responders, the median survival duration was 14.5 months (range, 3 to 28+), with four patients still alive. CONCLUSION Temozolomide in the schedule used has as good activity in chemotherapy-naive metastatic melanoma as the other most active agents currently in use. Further studies of the drug on its own and in combination with other agents is recommended.
Perceptions of cancer patients and their physicians involved in phase I trials.
Authors: Daugherty C , Ratain M J , Grochowski E , Stocking C , Kodish E , Mick R , Siegler M 
Published: February 2017

PURPOSE In an attempt to understand some of the complex issues related to the participation of cancer patients in phase I trials, and the perceptions of patients toward these trials, we conducted a pilot survey study of 30 cancer patients who had given informed consent to participate in a phase I trial at our institution. Concurrently, the oncologists identified by the surveyed patients as responsible for their care were surveyed as well. PATIENTS AND METHODS Twenty-seven of 30 consecutive patients agreed to and completed the survey. Patients were surveyed before they received any investigational agents. Eighteen oncologists participated in this survey study. RESULTS Eighty-five percent of patients decided to participate in a phase I trial for reasons of possible therapeutic benefit, 11% because of advice/trust of physicians, and 4% because of family pressures. Ninety-three percent said that they understood all (33%) or most (60%) of the information provided about the trials in which they had decided to participate. Only 33% were able to state the purpose of the trial in which they were participating, with patients able to state the purpose of phase I trials being more educated (P = .01). Surveyed oncologists had wide-ranging beliefs regarding expectations of possible benefits and toxicities for their patients participating in phase I trials. CONCLUSION Cancer patients who participate in phase I trials are strongly motivated by the hope of therapeutic benefit. Altruistic feelings appear to have a limited and inconsequential role in motivating patients to participate in these trials. Cancer patients who participate in phase I trials appear to have an adequate self-perceived knowledge of the risks of investigational agents. However, only a minority of patients appear to have an adequate understanding of the purpose of phase I trials as dose-escalation/dose-determination studies.