bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group.
Authors: Stewart S , Jablonowski H , Goebel F D , Arasteh K , Spittle M , Rios A , Aboulafia D , Galleshaw J , Dezube B J 
Published: February 2017

PURPOSE Cytotoxic chemotherapy is frequently required for the more severe manifestations of human immunodeficiency virus (HIV)-related Kaposi's sarcoma. Combinations of bleomycin and vincristine (BV) or BV with the addition of doxorubicin (ABV) are the most commonly used regimens against which new treatments may be compared. We report a multicenter phase III study that compared pegylated liposomal doxorubicin (PLD) to the BV combination. PATIENTS AND METHODS We conducted a randomized study that compared PLD 20 mg/m2 with a combination of bleomycin 15 IU/m2 and vincristine 2 mg in 241 patients with HIV-related Kaposi's sarcoma. Both regimens were administered by intravenous infusion every 3 weeks for six cycles. RESULTS A total of 121 patients received PLD and 120 patients the BV combination. The response to PLD was superior to BV: 58.7% versus 23.3% (P < .001). Patients who were randomized to receive BV, however, were more likely to terminate treatment early because of an adverse event (26.7% v 10.7%), and fewer completed the full six cycles of treatment (30.8% v 55.4%). Treatment with BV was associated with a significantly higher incidence of peripheral neuropathy (P < .001), whereas PLD treatment was more commonly associated with neutropenia and delays in receiving treatment (P < or = .001). CONCLUSION Pegylated liposomal doxorubicin is an effective treatment for HIV-related Kaposi's sarcoma with a higher response rate than the BV combination. It is well tolerated but more myelosuppressive.
Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic nonseminomatous germ cell tumor: a Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study.
Authors: Kaye S B , Mead G M , Fossa S , Cullen M , deWit R , Bodrogi I , van Groeningen C , Sylvester R , Collette L , Stenning S , De Prijck L , Lallemand E , deMulder P 
Published: February 2017

PURPOSE The aim of this randomized trial was to assess the potential therapeutic advantage of an intensive induction-sequential chemotherapy schedule (bleomycin, vincristine, cisplatin [BOP])/etoposide, ifosfamide, cisplatin, and bleomycin [VIP-B]), compared with a regimen based on bleomycin, etoposide, and cisplatin (BEP) (BEP/etoposide and cisplatin [EP]) for the treatment of patients with poor-prognosis metastatic nonseminomatous germ cell tumors (NSGCTs). PATIENTS AND METHODS Patients had one or more of the following: a retroperitoneal mass > or = 10 cm in diameter; mediastinal or supraclavicular mass > or = 5 cm in diameter; at least 20 lung metastases (any size); liver, bone, or brain metastases; and serum beta human chorionic gonadotropin (betaHCG) > or = 10,000 IU/L or alfa fetoprotein (AFP) > or = 1,000 IU/L. A total of 380 patients were accrued between May 1990 and June 1994 into this joint Medical Research Council (MRC)/European Organization for Research and Treatment of Cancer (EORTC) trial; of these, nine patients were deemed ineligible. RESULTS There was no significant difference between the two arms in the proportion of patients who achieved a complete response (CR) with chemotherapy alone, ie, 79 of 185 assessable patients (57%) with BEP/EP and 72 of 186 (54%) with BOP/VIP-B (P = 0.687). With a median follow-up of 3.1 years (maximum, 5.8), a total of 107 patients (28%) had progressive disease. There was no significant difference in time to first disease progression, or failure-free or overall survival between the two arms (P = 0.21, 0.101, and 0.190, respectively). The 1-year failure-free survival rates for BEP/EP and BOP/VIP-B were 60% (95% confidence interval [CI], 53% to 67%) and 53% (95% CI, 47% to 61%). Grade 3 or 4 myelosuppression, febrile neutropenia, and weight loss were more pronounced with BOP/VIP-B than with BEP/EP, and there were more toxic deaths with BOP/VIP-B than BEP/EP (18 [9%] v nine [5%]). CONCLUSION The intensive BOP/VIP-B therapy was associated with more toxicity, but there was no evidence of an improvement in response rate or survival compared with treatment with BEP/EP.
Metastatic germ cell tumors: modeling for response to chemotherapy.
Authors: Bajorin D F , Mazumdar M , Meyers M , Motzer R J , Vlamis V , Lin P , Bosl G J 
Published: February 2017

PURPOSE This study sought to determine factors that predict response to chemotherapy for patients with advanced germ cell tumors (GCTs), to evaluate different methods by which serum tumor markers can be used to predict response independent of assay method, and to develop criteria to guide allocation to clinical trials. METHODS Pretreatment data from 796 patients treated with platinum-based chemotherapy on Memorial Hospital protocols from 1975 to 1990 were analyzed. Multivariate analyses were performed on a developmental data set (n = 597) to assess for independently significant predictors of response. Predictive models developed using these methods were confirmed on the validation set (n = 199). RESULTS Independently significant factors for response included a mediastinal primary tumor (.015), pure seminomatous histology (.002), metastases to nonpulmonary visceral sites (bone, liver, and brain; .0001), and the pretreatment values of lactate dehydrogenase (LDH; .0001) and human chorionic gonadotropin (HCG; .0001). The likelihood of complete response (CR) was increased by seminomatous histology and decreased by the other factors. Serum levels of HCG and LDH could predict outcome independent of assay methodology. A model to predict good-, intermediate-, and poor-risk categories with CR rates of 92%, 76%, and 39%, respectively, was developed. CONCLUSION The independent prognostic factors of serum tumor markers LDH and HCG, the sites of metastases, and the primary origin of GCTs can predict outcome in patients with advanced GCT. These factors should be considered in the allocation of patients with advanced disease to clinical trials and have been included in the new tumor-node-metastasis (TNM) staging systems developed for the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC).
Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, and hydroxyurea with granulocyte colony-stimulating factor support for patients with poor-prognosis cancer of the head and neck.
Authors: Brockstein B , Haraf D J , Stenson K , Fasanmade A , Stupp R , Glisson B , Lippman S M , Ratain M J , Sulzen L , Klepsch A , Weichselbaum R R , Vokes E E 
Published: February 2017

PURPOSE We have previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (RT) (FHX). In the trial reported here, we added paclitaxel to the FHX base and used hyperfractionated RT to determine the maximum-tolerated dose (MTD), toxicities, and response rate in a poor-prognosis group of patients. METHODS Fifty-five patients who had either failed to respond to prior RT (n = 25) or surgery, had a coexistent or prior second malignancy, or who had unresectable or metastatic disease and an expected 2-year survival rate less than 10%, were treated. Chemoradiotherapy consisted of 2 Gy on days 2 to 6 (once-daily RT cohorts) or 1.5 Gy twice a day (hyperfractionated cohorts). Simultaneous HU (500 or 1,000 mg twice per day for 11 doses) and infusional 5-FU (600-800 mg/m2/d for 5 days) were given along with infusional paclitaxel at escalating doses of 5 to 25 mg/m2/d for 5 days. Granulocyte colony-stimulating factor (G-CSF) was administered on days 7 through 13 at 5 microg/kg/d. Cycles were repeated every 14 days until completion of RT. Plasma paclitaxel levels were determined on day 4 of cycle 1. RESULTS Dose-limiting toxicities (DLTs) consisted of myelosuppression, mucositis, dermatitis, and diarrhea. Plasma concentrations of paclitaxel greater than 10 nmol/L were achieved in 65% of patients at the recommended phase II dose (RPTD) level of paclitaxel. Seventy percent of assessable patients achieved a complete response (CR) to therapy. Twenty patients were treated at the RPTD of HU 500 mg orally twice daily for 11 doses, 5-FU 600 mg/m2/d by continuous infusion for 5 days; and paclitaxel 20 mg/m2/d by continuous infusion for 5 days, with twice-daily RT. CONCLUSION The addition of infusional paclitaxel and hyperfractionated RT to FHX is feasible. Radiosensitizing levels of paclitaxel are achieved in most patients. The high locoregional control rate of this regimen justifies further investigation in previously untreated patients.
Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study.
Authors: Perez E A , Hesketh P , Sandbach J , Reeves J , Chawla S , Markman M , Hainsworth J , Bushnell W , Friedman C 
Published: February 2017

PURPOSE The antiemetic effectiveness and safety of single-dose oral granisetron were compared with intravenous (I.V.) ondansetron in chemotherapy-naive patients who received moderately emetogenic chemotherapy. PATIENTS AND METHODS In this double-blind, parallel-group study, patients naive to emetogenic chemotherapy (N = 1,085) who were scheduled to receive cyclophosphamide- (500 to 1,200 mg/m2) or carboplatin (> or = 300 mg/m2) based chemotherapy, were randomized to receive either oral granisetron (n = 542) or I.V. ondansetron (n = 543). Efficacy assessments included the proportion of patients in each treatment group with total control over the 24 and 48 hours following chemotherapy initiation, as well as incidence and severity of nausea and emesis and use of antiemetic rescue medication. Prophylactic corticosteroids were allowed. Safety assessment was based on patients' reports of adverse experiences. RESULTS Approximately 80% of patients received prophylactic corticosteroids. Single-dose oral granisetron (2 mg) and I.V. ondansetron (32 mg) resulted in equivalent levels of total emetic control during the first 48 hours after chemotherapy. The proportion of nausea- and emesis-free patients at 24 and 48 hours were also approximately equivalent. The most commonly reported adverse experiences were headache, asthenia, and constipation. More patients who received ondonsetron than granisetron reported dizziness (9.6% v 5.4%, respectively; P = .011) and abnormal vision (4.2% v 0.6%, respectively; P < .001). CONCLUSION A single oral dose of granisetron (2 mg) resulted in equivalent levels of antiemetic protection as I.V. ondansetron (32 mg). Both agents were well tolerated, although more dizziness and abnormal vision were reported with ondansetron. Because the two antiemetic regimens exhibited equivalent efficacies, additional factors such as convenience and cost of therapy should be considered.
Prognostic significance of cathepsins B and L in primary human breast cancer.
Authors: Foekens J A , Kos J , Peters H A , Krasovec M , Look M P , Cimerman N , Meijer-van Gelder M E , Henzen-Logmans S C , van Putten W L , Klijn J G 
Published: February 2017

PURPOSE Evaluation of the clinical significance of cytosolic tumor levels of the lysosomal cysteine proteases cathepsin B (catB) and cathepsin L (catL) in patients with primary breast cancer. PATIENTS AND METHODS CatB (n = 1,500) and catL (n = 1,391) levels were determined by enzyme-linked immunosorbent assay (ELISA) in cytosols routinely prepared from frozen-tissue samples that were submitted to our laboratory for the assessment of steroid-hormone-receptor status. The median duration of follow-up of patients still alive at the time of analysis was 93 months. RESULTS Relating catB and catL levels with classical prognostic factors, the proteases were positively correlated with the number of positive lymph nodes (P < .01), and negatively with the level of steroid-hormone receptors (P < .01). We did not find a significant relationship between catB or catL levels with age and menopausal status of the patients or with the size of the primary tumor. The levels of catB and catL were positively correlated with each other and with the rates of relapse and death (all, P < .0001). In multivariate regression analysis for relapse-free survival (RFS) and overall survival (OS), corrected for the contribution of age/menopausal status, tumor size, the number of positive lymph nodes, and steroid-hormone-receptor status, catB and catL were significant predictors of the rates of relapse and death (all, P < .01). No statistically significant interactions of catB or catL with any of the classical prognostic factors or with each other were observed in their associations with the rates of relapse and death. CONCLUSION CatB and catL levels measured in routinely prepared cytosols are strong parameters to predict the rate of relapse and the length of survival after treatment of the primary breast tumor.
Bone metastases in patients with gastrinomas: a prospective study of bone scanning, somatostatin receptor scanning, and magnetic resonance image in their detection, frequency, location, and effect of their detection on management.
Authors: Gibril F , Doppman J L , Reynolds J C , Chen C C , Sutliff V E , Yu F , Serrano J , Venzon D J , Jensen R T 
Published: February 2017

PURPOSE To determine whether bone scan, magnetic resonance imaging (MRI), or somatostatin receptor scintigraphy (SRS) is best for identifying bone metastases in patients with gastrinomas, as well as their frequency and location, whether their detection affects management, and what patient subgroups should be examined. MATERIALS AND METHODS One hundred fifteen patients with gastrinoma were prospectively studied. Patients were examined yearly and those with liver metastases were reexamined every 3 months. Based on clinical history, histology, growth pattern, and development of new bone lesions, possible bone metastases were classified as to whether they were or were not bone metastases. Imaging results were correlated at different times in the disease course and with disease extent. RESULTS Bone scan was positive in 52 patients, MRI in seven, and SRS in six. Eight patients (7%) were determined to have bone metastases and MRI was correctly positive in seven, SRS in six, and bone scan in five. SRS or MRI was positive in all patients with bone metastases. Bone scan had significantly lower specificity and sensitivity, and a higher rate (P < .02) of false-negative results than MRI or SRS. Bone metastases occurred in 31% of patients with liver metastases and 0% with only lymph node metastases. The initial bone metastases were in the spine or sacrum (75%) followed in descending order by the pelvis or sacroiliac joints (38%), scapula or shoulder, and ribs. In all cases, detection of bone metastases changed the management. CONCLUSION SRS and MRI, because of high sensitivity and specificity, are recommended over bone scanning to screen for bone metastases in patients with gastrinomas. However, because bone metastases can occur initially outside the axial skeleton, SRS is the recommended initial localization method of choice. Bone metastases occur in 7% of all patients and 31% of patients with liver metastases, only occur in patients with liver metastases, are usually in the axial skeleton initially, and their detection changes management in all cases. Patients with pancreatic endocrine tumors with liver metastases should undergo SRS every 6 months to 1 year to detect bone metastases.
Molecular abnormalities in lung cancer.
Authors: Salgia R , Skarin A T 
Published: February 2017

PURPOSE To review several recently described molecular abnormalities in lung cancer and discuss their potential diagnostic and therapeutic relevance. DESIGN Articles were identified through a Medline search (1966 to 1997) and studies, including reviews, were cited in the references. RESULTS Molecular mechanisms altered in lung cancer include induced expression of oncogenes, such as RAS, MYC, c-erbB-2, and BCL-2, and loss of tumor-suppressor genes, such as RB, p53, and p16INK4A. RAS is a 21-kd G protein and up to 30% of adenocarcinomas show mutations in K-RAS oncogene. MYC encodes a transcriptional activator and amplification may adversely affect survival in small-cell lung cancer (SCLC). The growth factor receptor c-erbB-2 is overexpressed in up to 25% of non-small-cell lung cancer (NSCLC) cases. BCL-2, a negative regulator of apoptosis, is expressed differently in some NSCLCs. Abnormalities of RB, a key regulator of cell cycle, are detected in greater than 90% of SCLCs. There is an inverse relationship in lung cancer cells between expression of RB and p16INK4A, an upstream regulator of RB. Mutations of p53, with frequencies up to 50% in NSCLC and 80% in SCLC, can lead to loss of tumor-suppressor function, cellular proliferation, and inhibition of apoptosis. The identified molecular abnormalities in lung cancer are currently used to develop diagnostics for detecting early disease, as well as to identify targets for gene therapy. CONCLUSION Genetic abnormalities involved in the pathogenesis of lung cancer are rapidly being delineated. Understanding molecular abnormalities in lung cancer could potentially lead to earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.
Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin's disease: a meta-analysis of 23 randomized trials involving 3,888 patients. International Hodgkin's Disease Collaborative Group.
Authors: Specht L , Gray R G , Clarke M J , Peto R 
Published: February 2017

PURPOSE To assess the effect of more extensive radiotherapy and of adjuvant combination chemotherapy on long-term outcome of early-stage Hodgkin's disease. METHODS In a collaborative worldwide systematic overview, individual patient data were centrally reviewed on 1,974 patients in eight randomized trials of more versus less extensive radiotherapy and on 1,688 patients in 13 trials of radiotherapy plus chemotherapy versus radiotherapy alone. Crude mortality data on 226 patients in two other trials of chemotherapy were also reviewed. RESULTS More extensive radiotherapy reduced the risk of treatment failure (resistant or recurrent disease) at 10 years by more than one third (31.3% v 43.4% failures; P < .00001), but there was no apparent improvement in overall 10-year survival (77.1 % v 77.0% alive). The addition of chemotherapy to radiotherapy halved the 10-year risk of failure (15.8% v 32.7%; P < .00001), with a small, nonsignificant improvement in survival (79.4% v 76.5% alive). This involved a reduction of borderline significance for deaths from Hodgkin's disease (12.3% v 15.4% dead at 10 years; P = .07), which was partly counterbalanced by a nonsignificant excess of deaths from other causes (12.4% v 10.0% 10-year risk). CONCLUSION More extensive radiotherapy fields or the addition of chemotherapy to radiotherapy in the initial treatment of early-stage Hodgkin's disease had a large effect on disease control, but only a small effect on overall survival. Recurrences could be prevented by more extensive radiotherapy or by additional chemotherapy. However, if chemotherapy had not been given initially, recurrences were generally salvageable by re-treatment with chemotherapy. Hence, less intensive primary treatment--particularly a reduction in radiotherapy fields--appears to achieve similar survival rates as more intensive treatment, although more randomized evidence is needed to confirm this.
Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group.
Authors: Löwenberg B , Suciu S , Archimbaud E , Haak H , Stryckmans P , de Cataldo R , Dekker A W , Berneman Z N , Thyss A , van der Lelie J , Sonneveld P , Visani G , Fillet G , Hayat M , Hagemeijer A , Solbu G , Zittoun R 
Published: February 2017

PURPOSE AND METHODS Optimization of remission-induction and postremission therapy in elderly individuals with acute myeloid leukemia (AML) was the subject of a randomized study in patients older than 60 years. Remission-induction chemotherapy was compared between daunomycin (DNR) 30 mg/m2 on days 1, 2, and 3 versus mitoxantrone (MTZ) 8 mg/m2 on days 1, 2, and 3, both plus cytarabine (Ara-C) 100 mg/m2 on days 1 to 7. Following complete remission (CR), patients received one additional cycle of DNR or MTZ chemotherapy and were then eligible for a second randomization between eight cycles of low-dose (LD)-Ara-C 10 mg/m2 subcutaneously every 12 hours for 1 2 days every 6 weeks or no further treatment. RESULTS A total of 242 patients was randomized to DNR and 247 to MTZ. Median age of both study groups was 68 years. Secondary AML was documented in 26% and 25% of patients in either arm. The probability of attaining CR was greater (P = .069) with MTZ (47%) than with DNR (38%). Median duration of neutropenia was 19 (DNR) and 22 days (MTZ). The greater response rate to MTZ therapy correlated with reduced occurrence of chemotherapy resistance (32% v 47%, P = .001). With a median follow-up of 6 years, 5-year disease-free survival (DFS) is 8% in each arm. Overall survival estimates are not different between the groups (6% v 9% at 5 yrs). Poor performance status at diagnosis, high WBC count, older age, secondary AML, and presence of cytogenetic abnormalities all had an adverse impact on survival. Secondary AML and abnormal cytogenetics predicted for shorter duration of CR. Among complete responders, 74 assessable patients were assigned to Ara-C and 73 to no further therapy. Actuarial DFS was significantly longer (P = .006) for Ara-C-treated (13% [SE = 4.0%] at 5 years) versus nontreated patients (7% [SE = 3%]), but overall survival was similar (P = .29): 18% (SE = 4.6%) versus 15% (SE = 4.3%). Meta-analysis on the value of Ara-C postremission therapy confirms these results. CONCLUSION In previously untreated elderly patients with AML, MTZ induction therapy produces a slightly better CR rate than does a DNR-containing regimen, but it has no significant effect on remission duration and survival. Ara-C in maintenance may prolong DFS, but it did not improve survival.