bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved survival for patients with acute myelogenous leukemia.
Authors: Mitus A J , Miller K B , Schenkein D P , Ryan H F , Parsons S K , Wheeler C , Antin J H 
Published: February 2017

PURPOSE Despite improvement in chemotherapy and supportive care over the past two decades, overall survival for patients with acute myelogenous leukemia (AML) remains poor; only 25% to 30% of individuals with this disorder will be cured. In 1987, we initiated a prospective multiinstitution study designed to improve long-term survival in adults with AML. METHODS We modified the usual 7-day treatment scheme of daunorubicin and cytarabine with high-dose cytarabine (HiDAC) on days 8 through 10 (3 + 7 + 3). Allogeneic or autologous bone marrow transplantation (BMT) was offered to all patients who entered complete remission (CR) to decrease the rate of leukemic relapse. Data were analyzed by intention to treat. RESULTS CRs were achieved in 84 of 94 patients (89%; 95% confidence interval [CI], 83 to 95). Because of the high remission rate, factors previously thought to predict outcome, such as cytogenetics, WBC count, French-American-British (FAB) classification, sex, and age, were not useful prognostic variables. The overall survival rate for the entire cohort of patients from data of diagnosis is 55% at 5 years. Sixty percent of all patients who achieved a CR underwent marrow grafting. There was no significant difference in event-free survival (EFS) at 5 years comparing patients assigned to receive allogeneic BMT with patients assigned to receive autologous BMT (56% v 45%, P = .54). CONCLUSION The long-term disease-free survival observed in this study is excellent compared with historical data. This improvement in survival is probably due to the high rate of remission induction, as well as to the effective nature of the consolidation therapy.
2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia.
Authors: Saven A , Lemon R H , Kosty M , Beutler E , Piro L D 
Published: February 2017

PURPOSE 2-chlorodeoxyadenosine (2-CdA; cladribine) is a purine analog with activity in patients with chronic lymphocytic leukemia (CLL) who fail to respond to alkylator therapy. We conducted a phase II trial of 2-CdA in previously untreated CLL patients. PATIENTS AND METHODS 2-CdA was administered to 20 patients with previously untreated CLL as a 0.1-mg/kg/d 7-day continuous intravenous infusion every 28 to 35 days until maximum response or prohibitive toxicity. RESULTS A median of four courses (range, one to nine) was administered to each patient. Five patients (25%) achieved a complete response and 12 (60%) achieved a partial response, for an overall response rate of 85%. The median response follow-up duration was 8+ months (range, 3 to 27). Myelosuppression was the principal toxicity. Four of 20 patients (20%) experienced grade III or IV thrombocytopenia. Three patients, all of whom received corticosteroid therapy, developed opportunistic infections at a median of 19 months following discontinuation of 2-CdA therapy. CONCLUSION 2-CdA has major activity in patients with previously untreated CLL, and the lower response rates seen in previously treated patients may be due in part to poor marrow reserve from prior therapy. Determination of the relative effectiveness of 2-CdA, fludarabine, and chlorambucil in the treatment of CLL patients will require a randomized trial.
Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma.
Authors: Seymour J F , Talpaz M , Cabanillas F , Wetzler M , Kurzrock R 
Published: February 2017

PURPOSE Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic and prognostic significance in a number of disorders. The objective of this study was to examine the correlation between serum IL-6 levels and phenotypic characteristics, as well as outcome of patients with diffuse large-cell lymphoma (DLCL). PATIENTS AND METHODS Using an enzyme-linked immunosorbent assay (ELISA; lower limit of sensitivity, 0.35 pg/mL), we measured IL-6 levels in frozen sera from 33 healthy controls and 58 untreated patients with DLCL who were enrolled onto a single combination chemotherapy protocol. Serum IL-6 levels were correlated with clinical and laboratory features at diagnosis and with failure-free and overall survival. RESULTS Serum IL-6 levels in the lymphoma patients (median, 4.37 pg/mL; range, < 0.35 to 110 pg/mL) were significantly higher than in the control group (median, < 0.35 pg/mL; range, < 0.35 to 1.87 pg/mL) (P < .0001). Serum IL-6 levels were higher in patients with B symptoms (P = .012), an elevated beta 2-microglobulin level (> or = 3.0 mg/L) (P = .017), and a poor performance status (P = .02). Direct linear correlations with the erythrocyte sedimentation rate (ESR), platelet count, and total WBC count, and an inverse linear correlation with the serum albumin level, were observed (all P < .02). Patients with elevated serum IL-6 levels had inferior failure-free (P = .042) and overall survival (P = .05) compared with those with normal serum IL-6 levels. CONCLUSION In patients with DLCL, elevated serum levels of IL-6 at diagnosis are frequent, strongly associated with many adverse disease features, and predictive of a poor failure-free and overall survival.
Teniposide for brain metastases of small-cell lung cancer: a phase II study. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.
Authors: Postmus P E , Smit E F , Haaxma-Reiche H , van Zandwijk N , Ardizzoni A , Quoix E , Kirkpatrick A , Sahmoud T , Giaccone G 
Published: February 2017

PURPOSE Here we report the results of a phase II study of teniposide, one of the most active drugs against small-cell lung cancer (SCLC), in patients with brain metastases. PATIENTS AND METHODS Patients with SCLC who presented with brain metastases at diagnosis (n = 11) or during follow-up evaluation after treatment (n = 69) were treated with teniposide at a dose of 150 mg/m2 intravenously on days 1, 3, and 5 at 3-week intervals in an outpatient setting. Response in the brain was evaluated by brain computed tomography (CT) after two, six, and 12 courses. RESULTS In 26 of 80 assessable patients, an intracranial response was seen, with a response rate of 33% (95% confidence interval, 22% to 44%). The median response duration was 5.4 months for patients with a complete response (CR) and 4.2 months for patients with a partial response (PR). Patients who required corticosteroids for peritumoral edema had a significantly lower response rate than patients who did not receive corticosteroids. Neurologic function at the start of treatment had a significant influence (neurologic function 1 better than 2, respectively, better than 3 and 4; P < .001), as did the number of cycles of previous chemotherapy (0 better than 1 to 5 cycles, respectively, better than > 5 cycles; P = .043). Grade 3/4 leukocytopenia and thrombocytopenia were seen in 3% and 39%, respectively, of 80 patients. Toxicity-related death was seen in eight patients, seven of whom were previously treated with chemotherapy. CONCLUSION Teniposide is active against brain metastases of SCLC. It is a suitable drug for palliation, especially of patients without extensive pretreatment and with a good neurologic function and performance status. Patients previously treated with cranial radiotherapy are also candidates for this therapy. If systemic chemotherapy is considered for tumor progression outside the brain, radiotherapy of brain metastases might be omitted or delayed pending the effect of chemotherapy. The use of corticosteroids in patients with brain metastases treated with chemotherapy might influence the efficacy of the chemotherapy.
Plasma chromogranin A: a marker of serotonin release and of emesis associated with cisplatin chemotherapy.
Authors: Cubeddu L X , O'Connor D T , Parmer R J 
Published: February 2017

PURPOSE Emesis is a common side effect of cancer chemotherapy. Serotonin released from gastrointestinal enterochromaffin cells (ECC) may mediate chemotherapy-induced emesis. Since chromogranin A (CgA) is colocalized in ECC storage granules with serotonin, we tested the hypothesis that plasma CgA could mark emesis and serotonin release from ECC. PATIENTS AND METHODS The relationships between plasma CgA, serotonin release, and the development of vomiting following the first course of cisplatin chemotherapy were evaluated in 60 patients. RESULTS CgA levels increased in 59 of 60 patients (245% +/- 18% increase above baseline levels, P < .001). The time course of the increase in plasma CgA matched that of emesis and of urinary 5-hydroxyindoleacetic acid (5-HIAA). Significant (P < .001) positive correlations were found between the dose of cisplatin and the increases in plasma CgA, and between the changes in plasma CgA and urinary 5-HIAA after cisplatin (r = .54, n = 39, P < .001). The increase in plasma CgA after cisplatin did not correlate with changes in serum lactic dehydrogenase (LDH) activity, a marker of cell toxicity or lysis. CONCLUSION Plasma CgA marks emesis and serotonin release induced by cisplatin. Since both CgA and serotonin are costored in ECC granules, we suggest that the source of release of each may be the ECC. Increases in plasma CgA are not explained by drug cytotoxicity. Exocytosis appears as the main mechanism by which cisplatin releases serotonin. This work further supports the role of serotonin as a mediator of emesis associated with cisplatin and suggests that plasma CgA level is a valuable tool in studies of chemotherapy-induced emesis.
Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy.
Authors: Fyfe G , Fisher R I , Rosenberg S A , Sznol M , Parkinson D R , Louie A C 
Published: February 2017

PURPOSE To determine the efficacy and toxicity of a high-dose interleukin-2 (IL-2) regimen in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Proleukin (aldesleukin; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous (i.v.) infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. RESULTS The overall objective response rate was 14% (90% confidence interval [CI], 10% to 19%), with 12 (5%) complete responses (CRs) and 24 (9%) partial responses (PRs). Responses occurred in all sites of disease, including bone, intact primary tumors, and visceral metastases, and in patients with large tumor burdens or bulky individual lesions. The median response duration for patients who achieved a CR has not been reached, but was 19.0 months for those who achieved a PR. Baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was the only predictive prognostic factor for response to IL-2. While treatment was associated with severe acute toxicities, these generally reversed rapidly after therapy was completed. However, 4% of patients died of adverse events judged to be possibly or probably treatment-related. CONCLUSION High-dose IL-2 appears to benefit some patients with metastatic renal cell carcinoma by producing durable CRs or PRs. Despite severe acute treatment-associated toxicities, IL-2 should be considered for initial therapy of patients with appropriately selected metastatic renal cell carcinoma.
Pain and depression in patients with newly diagnosed pancreas cancer.
Authors: Kelsen D P , Portenoy R K , Thaler H T , Niedzwiecki D , Passik S D , Tao Y , Banks W , Brennan M F , Foley K M 
Published: February 2017

PURPOSE To evaluate the prevalence of pain and depression, their correlation, and their effect on quality of life in patients with recently diagnosed adenocarcinoma of the pancreas (PC). MATERIALS AND METHODS Cross-sectional pain and psychosocial distress were assessed using validated instruments, including the Memorial Pain Assessment Card (MPAC), Beck Depression Inventory (BDI), Hopelessness Scale (BHS), and Functional Living Index-Cancer (FLIC). Patients were evaluated before their first operation for PC or first treatment with chemotherapy at a large tertiary-care cancer center. RESULTS One hundred thirty patients with proven PC were studied: 83 before their operation and 47 before their first chemotherapy treatment. At the time of study entrance, 37% of patients had no pain and an additional 34% had pain that was mild or less severe. Only 29% of patients had moderate, strong, or severe pain. Chemotherapy patients reported significantly more intense pain than did preoperative patients (P = .02). Symptoms of depression were assessed using the BDI and BHS scales. A substantial minority of patients (38%) had BDI scores > or = 15, which suggests high levels of depressive symptoms. There was a significant correlation between increasing pain and depressive symptoms among those who experienced pain. Quality of life was assessed using the Weekly Activity Checklist (WAC) and the FLIC. Compared with patients who had no pain or mild pain, patients with moderate or greater pain had significantly impaired functional activity (P = .03) and poorer quality-of-life scores (P = .02) when compared with those with lesser degrees of pain. There were significant correlations between increasing pain and depression and between pain and depressive symptoms and impaired quality of life and function. CONCLUSION Our results indicate that moderate or severe pain and symptoms of depression are not as prevalent in recently diagnosed PC patients as is generally believed. However, one third have inadequate pain control despite the use of oral analgesics. These patients can be identified by the use of a simple self-report instrument (the MPAC card). Quality of life and function are adversely affected by moderate or greater levels of perceived pain intensity. A simple and rapid assessment is possible and can identify high-risk patients in need of intervention that may improve quality of life.
Implications of the p53 tumor-suppressor gene in clinical oncology.
Authors: Chang F , Syrjänen S , Syrjänen K 
Published: February 2017

PURPOSE The p53 gene encompasses 16 to 20 kb of DNA on the short arm of human chromosome 17. It encodes for a 393-amino acid nuclear phosphoprotein involved in cell-cycle control. Loss of normal p53 function is associated with cell transformation in vitro and development of neoplasms in vivo. During the past few years, the dramatic progress in the molecular biology of p53 has raised the exciting prospect for cancer management. The purpose of this review is to assess the potential role of p53 in clinical oncology. DESIGN Data on the alterations in the p53 gene in human cancers, with special emphasis on the clinical implications of changes in the p53 gene in the pathogenesis, diagnosis, prognosis, and therapy of human cancers, are summarized in this review. RESULTS AND CONCLUSION Current evidence suggests that abrogation of normal p53 pathway is a common feature in human cancers, and it appears to be a critical step in the pathogenesis and progression of tumors. Analysis of p53 function and mutations in human cancers may lead to identification of the precise nature of the carcinogenic damage in human tissues. These laboratory investigations and biologic findings have raised the possibility to screen patients at increased risk for cancer, aid the diagnosis made by traditional methods, assess the prognosis of individual cancer patient, design treatment protocols, and test the response to therapeutic agents.
Clinical applications of hematopoietic growth factors.
Authors: Vose J M , Armitage J O 
Published: February 2017

PURPOSE AND DESIGN To review the current clinical uses, ongoing investigations, and future applications of hematopoietic growth factors. Approved cytokines, as well as cytokines not yet released for general use, are included in this review. RESULTS Clinical applications of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin, the three recombinant hematopoietic growth factors currently commercially available for clinical use in the United States, are discussed. Macrophage colony-stimulating factor (M-CSF), interleukin-3 (IL-3), PIXY321, stem-cell factor (SCF), IL-1, IL-6, and IL-11 represent cytokines not yet approved; the majority of these newer agents have their principal action at an earlier time point in the hematopoietic cascade than the currently approved cytokines. Current clinical uses of hematopoietic growth factors include decreasing cytopenias associated with chemotherapy, those due to congenital or acquired bone marrow failure states, those that occur after high-dose chemotherapy and bone marrow transplantation, peripheral-blood progenitor mobilization, and supportive care of leukemia patients. CONCLUSION Hematopoietic growth factors have made a significant impact on the prevention of infections associated with chemotherapy-induced neutropenia, shortening of neutropenia following high-dose chemotherapy and progenitor-cell transplantation, and chemotherapy-associated anemia. Cost-effectiveness and cost-benefit analyses in future phase III and pharmacologic studies will aid in the assessment of these agents.
Four-step high-dose sequential chemotherapy with double hematopoietic progenitor-cell rescue for metastatic breast cancer.
Authors: Patrone F , Ballestrero A , Ferrando F , Brema F , Moraglio L , Valbonesi M , Basta P , Ghio R , Gobbi M , Sessarego M 
Published: February 2017

PURPOSE High-dose chemotherapy produces high complete remission (CR) rates and some survival advantage in patients with metastatic breast cancer (BC). A current issue is the possibility that these patients may have an even better prognosis with multiple high-dose treatments. In this study, we evaluated the feasibility of a four-step, high-dose sequential chemotherapy (HDSC) with double autologous hematopoietic progenitor-cell rescue. We also tested the hypothesis that peripheral-blood progenitor cells (PBPCs) harvested following a single recruitment with cyclophosphamide (CY) and granulocyte-macrophage colony-stimulating factor (GM-CSF) allow the safe administration of the whole HDSC with closely timed repeated courses of several non-cross-resistant agents. PATIENTS AND METHODS The treatment plan included CY 7 g/m2, followed by GM-CSF 5 to 7 micrograms/kg/d administered by continuous intravenous (i.v.) infusion on days 2 to 14; PBPCs with or without bone marrow (BM) harvest; mitoxantrone (NOV) 60, 75, or 90 mg/m2 plus melphalan (L-PAM) 140 to 180 mg/m2 with hematopoietic rescue; methotrexate (MTX) 8 g/m2 plus vincristine (VCR) 1.4 mg/m2; and etoposide (VP-16) 1.5 g/m2 plus carboplatin (PP) 1.5 g/m2 with hematopoietic rescue. RESULTS All 15 patients enrolled completed the entire treatment and there were no toxic deaths. Hematologic reconstitution was good at each step. The median number of days with an absolute neutrophil count (ANC) less than 100/microL and platelet count less than 20,000/microL were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after VP-16 plus PP. The main non-hematologic toxicity was mucositis, while organ toxicity was mild and reversible. CONCLUSION This regimen is feasible, with acceptable toxicity. GM-CSF and PBPCs have a pivotal role, as they hasten hematologic reconstitution, abate toxicity, and allow rapid recycling.
Phase II study of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer. Southern Osaka Lung Cancer Study Group.
Authors: Furuse K , Kubota K , Kawahara M , Kodama N , Ogawara M , Akira M , Nakajima S , Takada M , Kusunoki Y , Negoro S 
Published: February 2017

PURPOSE To evaluate the response rate, toxicity, and 2-year survival rate of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Between July 1989 and October 1990, 65 patients with histologically or cytologically proven unresectable stage III NSCLC without T3N0-1M0 disease were entered onto this study. Sixty-one patients were eligible for response, survival, and toxicity analysis. Chemotherapy consisted of vindesine (3 mg/m2 on days 1, 8, 29, and 36), cisplatin (100 mg/m2 on days 1 and 29), and mitomycin (8 mg/m2 on days 1 and 29). Radiotherapy was administered for 3 weeks (2 Gy given 13 times, five fractions per week), followed by 10-day rest periods and then the previous schedule of radiotherapy repeated for 3 weeks. RESULTS Of 61 eligible patients, 53 (86.9%) had a partial response (PR). The median response duration was 39.1 weeks (range, 8.4 to 163+). The median survival time was 16 months and the 2-year survival rate was 36.7%. Of 53 responding patients, 10 (16.4%) are alive and disease-free after 2 years. The major toxicity was leukopenia (> or = grade 3, 95%). Other toxicities of > or = grade 3 included thrombocytopenia (45%), anemia (28%), nausea/vomiting (16%), fever (11%), and esophagitis (6%). Treatment-related death occurred in two patients. One patient died of pulmonary toxicity (interstitial pneumonitis) and the other of esophagobronchial fistula with pulmonary infection. CONCLUSION Concurrent radiotherapy plus chemotherapy with mitomycin, vindesine, and cisplatin (MVP) can be safely administered to patients with stage III NSCLC, with excellent response rates and 2-year survival rates.
Attitudes and behaviors on physician-assisted death: a study of Michigan oncologists.
Authors: Doukas D J , Waterhouse D , Gorenflo D W , Seid J 
Published: February 2017

PURPOSE To ascertain the attitudes of oncologists toward physician-assisted death, ie, physician-assisted suicide and active euthanasia, as well as their experiences with these activities and their opinions toward their legalization. METHODS A survey was mailed to all practicing 250 oncologists in the state of Michigan, with subsequent development of psychometric scales and their correlation with self-reported behaviors in physician-assisted death. RESULTS Analysis revealed five distinct, meaningful factors regarding approval or disapproval of physician-assisted death. These factors reflected global attitudes toward physician-assisted death, passive euthanasia, philosophical prohibitions toward physician-assisted death, concerns of legal consequences with physician-assisted death, and attitudes that physician-assisted death could be avoided with better end-of-life care (alpha = .94, .74, .76, .87, and .84, respectively). High levels of therapy withdrawal were reported (81%), with significant reservations toward assisted suicide and active euthanasia, although reported participation in such actions was noteworthy (18% and 4%, respectively). The scales reflecting global and philosophical attitudes correlated with several attitudes and behaviors toward physician-assisted death (P < .001). Legislation that would allow physician-assisted death was favored by 20.8% of respondents. CONCLUSION Although they have reservations about physician-assisted death, significant numbers of oncologists are willing to consider such actions should they become legal. Given the substantial number of physicians who report that they have already participated in physician-assisted death, these findings may help better understand the attitudes that motivate physician behaviors toward assisted death.