bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of interleukin-2 and lymphokine-activated killer cells for the treatment of patients with non-Hodgkin's lymphoma.
Authors: Weber J S , Yang J C , Topalian S L , Schwartzentruber D J , White D E , Rosenberg S A 
Published: February 2017

PURPOSE The study was undertaken to assess whether immunotherapy regimens with bolus high-dose interleukin-2 (IL-2) alone or with lymphokine-activated killer (LAK) cells are active in previously treated, relapsed patients with non-Hodgkin's lymphoma. PATIENTS AND METHODS Nineteen patients with low- or intermediate-grade lymphomas were treated with bolus high-dose IL-2 alone (11 patients) or IL-2 with LAK cells (eight patients). IL-2 was administered by intravenous bolus infusion at 720,000 IU/kg every 8 hours. Eight patients had low-grade histologies; 11 patients were intermediate-grade. Eighteen patients had received second- or third-generation combination chemotherapy, and eight had also received radiation. All 19 relapsed after a median of two chemotherapy regimens. RESULTS Four responses were observed, three partial and one complete, in patients with follicular histologies who received IL-2 with LAK cells. Response durations were 10, 16, 16, and 26 months, and three responders were re-treated after relapse with subsequent disease control for an additional 16, 39+, and 2+ months, respectively. CONCLUSION High-dose, bolus IL-2-based immunotherapy with LAK cells may be an effective treatment for patients with non-Hodgkin's lymphoma and merits further testing with larger numbers of patients in phase II trials.
High-risk multiple myeloma treated with high-dose melphalan.
Authors: Lokhorst H M , Meuwissen O J , Verdonck L F , Dekker A W 
Published: February 2017

PURPOSE This study was undertaken to evaluate the efficacy and toxicity of high-dose melphalan (HDM) 140 mg/m2 in poor-risk multiple myeloma (MM). PATIENTS AND METHODS Thirteen patients were previously untreated, and 13 had been pretreated with vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) for refractory or relapsed MM. RESULTS All 11 fully assessed, untreated patients responded, and six achieved a complete response. Remissions were of excellent quality, but response duration--a median of 16 months--was short. This was probably due to the high incidence of unfavorable prognostic signs, like a high beta 2-microglobulin (B2M) and/or a high plasma cell labeling index (LI). None of the nine pretreated patients with a measurable M component had more than 50% reduction of M component after HDM, indicating that intensive treatment has no effect on a residual tumor population. The relapse-free period after HDM in this group of patients (median, 9 months) was not better than in a historical control group of patients treated with VAD alone. The major complications due to the prolonged myelosuppression were severe infections. After primary HDM, median time to recovery to greater than 0.5 x 16(9) granulocytes was 30 days; in previously treated patients, the recovery period was even longer. There were three toxic deaths. Fulminant relapses with features of J-chain disease were frequently observed, indicating a dedifferentiated tumor, probably induced or selected by the HDM. CONCLUSIONS HDM is an effective treatment resulting in good remissions for untreated MM. However, other therapy strategies should be explored first, focusing on the reduction of toxicity and prolongation of the relapse-free period, before HDM can be recommended as first-line treatment for the younger MM patient.
High-dose busulfan in patients with myeloma.
Authors: Mansi J , da Costa F , Viner C , Judson I , Gore M , Cunningham D 
Published: February 2017

PURPOSE To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance < 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.
High-Dose Chemotherapy With Autologous Bone Marrow Transplantation for the Treatment of Metastatic Breast Cancer
Authors: Eddy David M. 
Published: February 2017

Tables 1 to 4 contained errors in the report "High-Dose Chemotherapy With Autologous Bone Marrow Transplantation for the Treatment of Metastatic Breast Cancer" by Eddy (J Clin Oncol 10:657–670, 1992). They are reprinted here correctly in their entirety: Please see the PDF for Table.
Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party.
Authors: Read G , Stenning S P , Cullen M H , Parkinson M C , Horwich A , Kaye S B , Cook P A 
Published: February 2017

PURPOSE A prospective study of surveillance after orchidectomy alone in patients with stage I nonseminomatous germ cell testicular tumor (NSGCT) was performed to determine the relapse-free rate and to identify the histologic criteria that predict for relapse. PATIENTS AND METHODS Three hundred ninety-six patients from 16 United Kingdom and one Norwegian centers were entered onto the study between January 1, 1984 and October 1, 1987 of whom 373 were eligible for analysis. In a previous retrospective study, we defined a prognostic index based on histologic criteria that identified a group of patients with a high risk of relapse. This index was based on the presence of venous and lymphatic invasion, undifferentiated cells, and the absence of yolk sac elements in the primary tumor. RESULTS The 2-year actuarial relapse-free rate after orchidectomy was 75% (95% confidence interval, 71% to 79%), and the rate at 5 years was 73%. Five patients died of tumor or treatment-related complications, which resulted in a 5-year survival of 98%. The relapse-free rate in patients with three or four risk factors was 54%. CONCLUSIONS This study confirms the safety of surveillance as a method of management and identifies a group of patients with a high risk of relapse. A prospective phase II study has been initiated to determine whether two courses of platinum-based adjuvant chemotherapy will prevent relapse in these high-risk patients.
Suramin: rapid loading and weekly maintenance regimens for cancer patients.
Authors: van Rijswijk R E , van Loenen A C , Wagstaff J , Meijer E , Lopez R , van Groeningen C J , Heimans J J , Pinedo H M 
Published: February 2017

PURPOSE Suramin is an anticancer agent with a narrow therapeutic window and a terminal half-life of 45 to 55 days. These characteristics make it necessary to control accurately the serum concentrations of the drug. Therefore, the aim of the present study was to develop a rapid loading regimen, followed by weekly administration of suramin to maintain serum concentrations of between 150 and 300 micrograms/mL for 8 weeks. PATIENTS AND METHODS Eligible patients were treated with five different loading regimens. Initially, weekly maintenance doses were estimated manually by the treating physician. Subsequently, computer-assisted dosing that used Bayesian pharmacokinetic modeling was used. RESULTS Thirty-eight courses of suramin that were administered to 35 patients were studied. The optimal loading regimen consisted of a continuous infusion of 600 mg/m2 during a 24-hour period, which resulted in a mean serum concentration of 319 micrograms/mL. Potentially toxic concentrations that were observed with shorter infusions were avoided. Maintenance treatment, which used the weekly administration of suramin during a 6-hour period, seemed to be able to maintain mean suramin serum trough concentrations of 150 micrograms/mL, while preventing mean peak concentrations of more than 300 micrograms/mL. The use of Bayesian pharmacokinetics was superior to manual estimation in tailoring the optimal dose to the therapeutic window. CONCLUSIONS Continuous infusion is the optimal way of delivering suramin during the loading phase. To maintain trough levels and peak levels within a narrower therapeutic window, suramin will have to be administered more frequently than once a week. Bayesian modeling based on individual serum levels and population pharmacokinetics allows accurate dosing to maintain suramin levels within the therapeutic window.
Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.
Authors: Foss F M , Ihde D C , Breneman D L , Phelps R M , Fischmann A B , Schechter G P , Linnoila I , Breneman J C , Cotelingam J D , Ghosh B C 
Published: February 2017

PURPOSE This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment. RESULTS Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia. CONCLUSION These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.
The optimal timing of autologous bone marrow transplantation in Hodgkin's disease patients after a chemotherapy relapse.
Authors: Desch C E , Lasala M R , Smith T J , Hillner B E 
Published: February 2017

PURPOSE The optimal sequence of salvage chemotherapy (SC) and autologous bone marrow transplantation (ABMT) for Hodgkin's disease (HD) patients who relapse after primary chemotherapy is unknown. We created a decision analysis model to determine the optimal treatment strategy and the most cost-effective approach. METHODS The decision tree simulated a 25-year-old HD patient who relapsed less than 12 months after mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy. Four strategies used ABMT in some sequence with SC; the final strategy considered SC alone. Clinical data were derived from 17 published reports chosen by explicit criteria. Costs of care were estimated from the published literature and institutional experience. RESULTS The optimal strategy was ABMT in second relapse, which was superior to the SC-only option by 1.9 years at an incremental cost of $26,200 per each year of life saved. When the probabilities of complete remission and disease-free survival were reduced for SC, similar to the clinical expectation of SC after a seven- or eight-drug regimen like MOPP/doxorubicin, bleomycin, and vinblastine with or without dacarbazine (MOPP/ABV[D]), ABMT in first relapse was the preferred strategy and provided 6 additional months. However, when the data from favorable (or unfavorable) SC and ABMT reports were compared head-to-head in this model, SC followed by ABMT in second relapse was always optimal. CONCLUSIONS All relapsed HD patients should plan to use ABMT in some sequence with SC, if necessary. In most situations the optimal strategy is ABMT in second relapse. This analysis will assist clinicians in planning treatment for relapsed HD patients. It could be refined if historical series were updated to report the incidence and outcomes of SC relapse from seven- or eight-drug regimens.
Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure.
Authors: Longo D L , Duffey P L , Young R C , Hubbard S M , Ihde D C , Glatstein E , Phares J C , Jaffe E S , Urba W J , DeVita V T 
Published: February 2017

PURPOSE The study was undertaken to evaluate clinical prognostic factors, probability of response to therapy, duration of response, and overall survival of patients with Hodgkin's disease relapsing from a chemotherapy-induced complete remission. PATIENTS AND METHODS Study population comprised 107 patients with Hodgkin's disease treated with combination chemotherapy at the National Cancer Institute who relapsed after achieving a complete remission. RESULTS Half of the relapses occurred within the first year of achieving complete remission; among patients in remission 5 years or longer, only 4% relapsed. The overall survival of the relapsed patients is projected to be 17% at 20 years, calculated from the date of relapse. Primary treatment regimen, presence of B symptoms, stage, sex, liver involvement, pleural involvement, marrow involvement, and histologic subtype did not affect the survival of relapsed patients. Only age at diagnosis (older or younger than 30 years) and length of initial remission (shorter or longer than 1 year) made a significant impact on survival. Patients whose initial remission was longer than 1 year had significantly higher complete response rates to salvage therapy, significantly more durable second remissions, and significantly longer survival than patients whose initial remission was shorter than 1 year. Survival beyond 11 years from relapse of patients with long initial remissions was 24%; for those with short initial remissions, 11% (P2 = .027). Despite the fact that with salvage therapy, patients with long initial remission had an 85% complete response rate to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) with a disease-free survival of 45% at 20 years, acute leukemia and other treatment-related complications combined to lower the survival rate of this more favorable subset. CONCLUSIONS These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.
A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma.
Authors: Weiss G R , Margolin K A , Aronson F R , Sznol M , Atkins M B , Dutcher J P , Gaynor E R , Boldt D H , Doroshow J H , Bar M H 
Published: February 2017

PURPOSE Since 1985, multiple centers have demonstrated that interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells produce durable anticancer responses in patients with metastatic renal cell carcinoma. High-dose recombinant IL-2 (rIL-2) has been administered by intravenous bolus injection (Rosenberg SA, et al: N Engl J Med 313:1485-1492, 1985) and by continuous intravenous infusion (West WH, et al: N Engl J Med 316:898-905, 1987) combined with lymphokine-activated killer (LAK) cells, with both methods producing responses in patients with advanced renal cell carcinoma. The Extramural IL-2/LAK Working Group has conducted a randomized phase II trial of two intravenous high-dose rIL-2 regimens (bolus three times daily or 24-hour continuous infusion) to determine if either one manifests greater anticancer activity or a more acceptable toxicity profile. PATIENTS AND METHODS Ninety-four patients with measurable advanced renal cell carcinoma were enrolled on this study: 46 to the bolus injection arm and 48 to the continuous infusion arm. On both arms, patients underwent a priming phase of rIL-2 administration, four daily lymphocytaphereses to harvest mononuclear cells that were placed in 3- to 4-day culture for generation of LAK cells, and an rIL-2/LAK coadministration phase. Patients were then observed monthly for evidence of response to this therapy and were offered up to two additional courses of treatment every 3 months if evidence of response was detected. RESULTS Twenty percent of patients on the bolus injection arm experienced objective responses (three complete responses and six partial responses); 15% of patients on the continuous infusion arm responded (two complete responses and five partial responses). Complete responses were durable, persisting for 310+ to 700+ days. The incidence of severe life-threatening toxicities typical of high-dose rIL-2 therapy was similar in both arms (eg, patients with hypotension requiring pressors: bolus 71%, continuous 63%; oliguria less than or equal to 200 mL/8 hours: bolus 65%, continuous 71%). More episodes of fever, infection, and serum alkaline phosphatase elevation were associated with the continuous infusion arm, while more thrombocytopenia occurred on the bolus injection arm. Four patients (three bolus injection, one continuous infusion) died of respiratory and circulatory failure while under treatment. No clinical or laboratory parameter accompanying treatment on either arm was, by univariate or multivariate analysis, associated with an increased likelihood of response. CONCLUSIONS Both methods of high-dose rIL-2/LAK cell administration produce nearly equivalent anticancer activity and toxicity in the treatment of renal cell carcinoma. The ability to predict responding patients based on patient or treatment characteristics is not possible.
Increased teniposide clearance with concomitant anticonvulsant therapy.
Authors: Baker D K , Relling M V , Pui C H , Christensen M L , Evans W E , Rodman J H 
Published: February 2017

PURPOSE A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients. PATIENTS AND METHODS The systemic clearance of teniposide was determined in six pediatric patients with acute lymphocytic leukemia receiving concomitant therapy with anticonvulsants. Clearance was then compared with a control group of patients treated with the same protocol therapy and matched for age at diagnosis, sex, and race but not receiving anticonvulsants or other agents known to induce hepatic metabolism or alter protein binding of drugs. Eight blood samples were obtained during and after 4-hour infusions of teniposide, and plasma concentrations were measured by a specific high-performance liquid chromatography (HPLC) assay. A two-compartment model was fitted to each subject's data. RESULTS The mean systemic clearance (range) for the six anticonvulsant-treated patients studied during 22 courses of therapy was 32 mL/min/m2 (range, 21 to 54 mL/min/m2), significantly higher (P less than .001) than the mean value of 13 mL/min/m2 (range, 7 to 17 mL/min/m2) for the control patients studied during 26 courses of therapy. Clearance estimates for control patients were similar to previously published values for pediatric patients. CONCLUSION These data indicate that the systemic clearance of teniposide is consistently increased two- to three-fold by concomitant phenobarbital or phenytoin therapy. The consequent substantial reduction in systemic exposure may reduce teniposide's efficacy.
Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study.
Authors: Biti G P , Cimino G , Cartoni C , Magrini S M , Anselmo A P , Enrici R M , Bellesi G P , Bosi A , Papa G , Giannarelli D 
Published: February 2017

PURPOSE To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT. PATIENTS AND METHODS From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44). RESULTS All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02). CONCLUSION We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors.