bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis and other clinical correlates of pathologic review in stage I and II testicular carcinoma: a report from the Testicular Cancer Intergroup Study.
Authors: Sesterhenn I A , Weiss R B , Mostofi F K , Stablein D M , Rowland R G , Falkson G , Rivkind S E , Vogelzang N J 
Published: February 2017

PURPOSE The Testicular Cancer Intergroup Study (TCIS) was undertaken to evaluate the pathologic findings in early-stage testicular cancer as determined by central pathology review, to compare these findings with the interpretation by the contributing pathologists, and to make correlations with various clinical parameters and outcomes. PATIENTS AND METHODS The prospective study of non-seminomatous germ cell testicular cancer staged surgically involved 459 eligible patients with stage I (node-negative) or stage II (node-positive) disease. Pathologic materials from both the orchiectomy and lymphadenectomy specimens were submitted to a central laboratory for evaluation. RESULTS Central and local pathologists differed significantly in their identification of certain cellular histologies (primarily yolk sac tumors [YST]) and recognition of invasion into vascular structures. In contrast to our prior findings with local pathologic assessment, venous/lymphatic invasion as determined by central review predicted relapse in both stages. In pathologic stage I disease, the relapse rate was 19.4% (12 of 62 cases) for those with invasion versus 6.0% (10 of 168 cases) for those without invasion. In pathologic stage II disease, the respective relapse rates were 63.5% (40 of 63 cases) and 24.0% (six of 25 cases). Vascular invasion was jointly predictive with nodal stage for risk of relapse. The percentage of embryonal carcinoma (EC) in the primary tumor was predictive of nodal stage and relapse in a univariate, but not a multivariate, analysis. In a large substudy, immunohistochemical staining identified a correlation between stain intensity in YST and serum alpha-fetoprotein (AFP) levels. In a similar fashion human chorionic gonadotropin (HCG) staining reactivity occurred exclusively in patients with syncytiotrophoblasts and correlated with serum levels of beta-HCG. CONCLUSIONS A number of tumor histology correlates with clinical parameters have been identified or confirmed. Careful pathologic scrutiny of the primary testicular tumor, especially for vascular invasion, provides important prognostic information.
Adjuvant therapy with escalating doses of doxorubicin and cyclophosphamide with or without leukocyte alpha-interferon for stage II or III breast cancer.
Authors: Buzdar A U , Hortobagyi G N , Kau S W , Smith T L , Fraschini G , Holmes F A , Gutterman J U , Hug V M , Singletary S E , Ames F C 
Published: February 2017

PURPOSE A prospective study in breast cancer patients was undertaken to determine whether escalating doses of doxorubicin and cyclophosphamide would result in a higher fraction of patients free of disease, and to evaluate the role of leukocyte alpha-interferon. PATIENTS AND METHODS Between 1982 and 1986, 319 consecutive patients with stage II or III breast cancer with one or more positive nodes were assigned randomly to receive adjuvant chemotherapy that consisted of escalating doses of doxorubicin and cyclophosphamide in combination with vincristine and prednisone or the same chemotherapy regimen followed by 1 year of leukocyte alpha-interferon. Doxorubicin was administered by 72-hour continuous infusion through a central venous catheter (maximum total cumulative dose, 430 mg/m2). All patients with positive or unknown estrogen receptor status were also given tamoxifen for 1 year. RESULTS The median follow-up was 71 months (range, 35 to 99 months). Correlation of disease-free survival (DFS) with dose-intensity of cyclophosphamide and doxorubicin showed no improvement in DFS for patients who were able to receive escalated drug doses compared with those who were not. Doxorubicin administered by continuous infusion was associated with a negligible risk of cardiotoxicity in this study despite the administration of higher accumulative doses than in our previous adjuvant therapy studies. The DFS rates of patients who did and those who did not receive leukocyte alpha-interferon were similar. CONCLUSIONS In this study, there was no real evidence that higher drug dose intensity was associated with longer DFS. Leukocyte alpha-interferon as it was used in this study had no therapeutic value. Doxorubicin administered by infusion was associated with a reduced risk of cardiotoxicity.
Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients treated with the LNH-84 regimen.
Authors: Bosly A , Coiffier B , Gisselbrecht C , Tilly H , Auzanneau G , Andrien F , Herbrecht R , Legros M , Devaux Y , Jaubert J 
Published: February 2017

PURPOSE Of the 737 patients with aggressive lymphoma who were treated with the LNH-84 regimen, 244 with progressive disease after complete remission or partial response were analyzed retrospectively to determine the influence of intensive chemotherapy with bone marrow transplantation (BMT) on survival. PATIENTS AND METHODS Forty-four patients were treated with salvage chemotherapy, followed by autologous bone marrow transplantation (ABMT) in 40 and allogeneic BMT in four. The other 200 patients were treated with chemotherapy only. RESULTS Salvage treatment produced an objective response in 57% of the patients; 23% achieved a second complete remission. Median overall survival was longer for patients who were treated with ABMT than for those who were treated with chemotherapy only (12.4 v 6.7 months), as was median freedom from progression (FFP) survival (7.7 v 4 months). In multiparametric analysis, ABMT and normal initial lactic dehydrogenase (LDH) level were the primary parameters associated with longer survival. This is also true when (1) only patients younger than 60 years of age, (2) only patients who responded to salvage regimen, or (3) only patients with both conditions were included in the analysis. Patients who were not transplanted had a 1.69 to 2.26 relative risk of dying from their disease compared with those who were treated with intensive chemotherapy plus ABMT. CONCLUSION This study produced more evidence of the favorable impact of intensive chemotherapy with bone marrow rescue on survival in lymphoma patients who had relapsed.
Feasibility of using quinine, a potential multidrug resistance-reversing agent, in combination with mitoxantrone and cytarabine for the treatment of acute leukemia.
Authors: Solary E , Caillot D , Chauffert B , Casasnovas R O , Dumas M , Maynadie M , Guy H 
Published: February 2017

PURPOSE We demonstrated previously that sera from quinine-treated patients reversed the multidrug resistance (MDR) of a human leukemic cell line. We now report a phase I and II clinical study that examined the toxicity of the combination of quinine with mitoxantrone and cytarabine (Ara-C). PATIENTS AND METHODS Fifteen adult patients with relapsed or refractory acute leukemia were treated with quinine formiate (30 mg/kg/d in continuous intravenous (IV) infusion from day 1 through day 5 or 6) associated with Ara-C (1 g/m2 in 3-hour IV infusion twice a day for 5 days) and five increasing doses of mitoxantrone (from 8 mg/m2/d for 4 days to 12 mg/m2/d for 5 days). RESULTS The main toxicity was severe myelosuppression: the mean times to leukocyte recovery (> 500/microL), granulocytes recovery (> 500/microL), and platelet count recovery (> 50,000/microL) were 23 days (range, 17 to 29 days), 30.6 days (range, 17 to 48 days), and 35.4 days (range, 14 to 75 days), respectively. The nonhematopoietic toxicity of this regimen was acceptable. Nausea and vomiting were common, but severe mucositis was observed in only two patients. Cardiotoxicity was limited to transient episodes of moderate supraventricular tachycardia and a clinically well-tolerated bradycardia. Tinnitus and vertigo were observed in 10 cases (67%), and mild hearing loss and transient increase of serum bilirubin were observed in six patients (40%). Total quinine serum levels reached a steady-state concentration between 6.4 and 18 mg/L in 24 hours. Complete remission (CR) was achieved in eight of 14 (57%) assessable patients, and partial response (PR) was achieved in two additional patients (14%). P-glycoprotein expression was detected on blast cells from five of 13 studied patients before treatment. A response was observed in all P-glycoprotein-positive cases. CONCLUSION Quinine can be used safely as a potential reversing agent of MDR for the treatment of clinically resistant acute leukemias.
Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study.
Authors: de Forni M , Malet-Martino M C , Jaillais P , Shubinski R E , Bachaud J M , Lemaire L , Canal P , Chevreau C , Carrié D , Soulié P 
Published: February 2017

PURPOSE A prospective clinical study was performed to determine the incidence of high-dose continuous intravenous infusion fluorouracil (5FU-CIV) cardiotoxicity. PATIENTS AND METHODS Three hundred sixty-seven patients who were given first-cycle high-dose 5FU-CIV were monitored for cardiac function by clinical examination, ECG, and laboratory tests. 5FU-CIV was administered during a 96- or 120-hour period at doses that ranged from 600 to 1,000 mg/m2/d. Associated drugs included cisplatin (56%), mitomycin (12.5%), folinic acid (leucovorin) (7%), and others (14%). Thirty-nine patients (10.5%) received 5FU as a single agent. RESULTS 5FU-induced cardiac events occurred in 28 patients (7.6%; 95% confidence interval, 4.9% to 10.3%). Nine of them had a history of cardiac disease. Primary tumors included head and neck (n = 13), gastrointestinal (n = 6), breast (n = 3), and others (n = 6). The mean onset time of cardiac symptoms was 3 days (range, 2 to 5). Inaugural symptoms included angina pectoris (n = 18), hypotension (n = 6), hypertension (n = 5), malaise (n = 4), dyspnea (n = 2), arrhythmia (n = 1), or sudden death (n = 1). At 5FU discontinuation, six patients' cardiac symptoms returned to baseline, but 21 patients experienced unstable angina (n = 8), hypotension/cardiovascular collapse (n = 11), pulmonary edema (n = 1), or sudden death (n = 4). The lethality rate was 2.2% (five sudden deaths plus three irreversible collapses). ECG showed repolarization changes (ST segment deviation; T-wave inversion) in 65% and/or diffuse microvoltage in 22% of the patients who presented with cardiac events. Echocardiography showed partial or global hypokinesia in nine of the 16 patients who were examined, and one case of prolonged akinesia. Cardiac enzymes rarely showed an increase (n = 2). In severe but reversible cases, clinical, ECG, and echographic parameters returned to baseline status within 48 hours after the drug discontinuation. A fluorine 19 nuclear magnetic resonance (19F NMR) analysis of urine was performed on 14 patients; six had cardiac symptoms and eight did not. Fluoroacetate (FAC), a known cardiotoxic compound, was detected in all cases. CONCLUSION In our study, the incidence of high-dose 5FU-CVI cardiotoxicity was 7.6%. The hypothesis of a toxic cardiomyopathic process requires further confirmation.
Adjuvant therapy with a doxorubicin regimen and long-term tamoxifen in premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial.
Authors: Tormey D C , Gray R , Abeloff M D , Roseman D L , Gilchrist K W , Barylak E J , Stott P , Falkson G 
Published: February 2017

PURPOSE A randomized trial was performed in premenopausal postoperative women with ipsilateral axillary node-positive (N+) breast carcinoma and known estrogen receptor (ER) status to assess the efficacy of an Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-based induction regimen and 5 or more years of tamoxifen (Tam). PATIENTS AND METHODS Patients received 12 28-day cycles of cyclophosphamide 100 mg/m2 orally days 1 to 14, methotrexate 40 mg/m2 intravenously (IV) days 1 and 8, fluorouracil 600 mg/m2 IV days 1 and 8, prednisone 40 mg/m2 orally days 1 to 14, and Tam 10 mg orally twice daily (CMFPT), or the same regimen plus halotestin 10 mg orally twice daily (CMFPTH) alternating monthly with 22-day cycles of vinblastine 4.5 mg/m2 IV day 1, Adriamycin 45 mg/m2 IV day 1, thiotepa 12 mg/m2 IV day 1, halotestin, and Tam (ALTER). Prednisone in the ALTER regimen was stopped after the second CMFPTH cycle. After 12 cycles, patients were again randomized to stop or continue Tam. After 5 years, patients on Tam were again randomized to continue or stop Tam; the results from this randomization are still coded. Among 533 analyzed induction cases, 263 received CMFPT and 270 ALTER. Among 396 analyzed maintenance cases, 201 continued Tam and 195 were observed. Pretreatment characteristics were balanced among treatments. The median follow-up times are 5.1 years for induction and 4.1 years for maintenance. RESULTS The time to relapse (TTR) was superior for the ALTER regimen (P = .04) and for the maintenance Tam (P = .05). Overall survival comparisons between the regimens are not statistically different. A longer TTR was associated with decreasing nodal involvement, ER+ status, and increasing age. The favorable effects of decreasing nodal involvement and ER+ status carried over to survival; a progesterone receptor-positive (PgR+) status and decreasing tumor size were also associated with longer survival. Development of amenorrhea was associated with improved TTR and survival. Toxicity was similar for the two induction regimens and for the two maintenance regimens. Overall relapse patterns were similar among the induction regimens, but continuing Tam led to fewer locoregional relapses. CONCLUSION The results suggest significant overall TTR therapeutic benefits of an Adriamycin-containing alternating induction regimen and of continuing maintenance Tam therapy for at least 5 years.
Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting.
Authors: Beck T M , Hesketh P J , Madajewicz S , Navari R M , Pendergrass K , Lester E P , Kish J A , Murphy W K , Hainsworth J D , Gandara D R 
Published: February 2017

PURPOSE This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis. PATIENTS AND METHODS This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy-naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.15 mg/kg times three doses, every 4 hours or a single 8-mg or 32-mg dose followed by two saline doses that began 30 minutes before cisplatin administration. Cisplatin (high-dose > or = 100 mg/m2 or medium-dose 50 to 70 mg/m2) was given as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 hours after cisplatin administration. RESULTS A total of 699 patients (359 high-dose, 340 medium-dose) were enrolled. Of these, 618 were assessable for efficacy (15 ineligible, 66 protocol deviations). The 32-mg dose was superior to the 8-mg single dose with regard to total number of emetic episodes (high-dose, P = .015; medium-dose, P < .001), complete response (no emetic episodes: high-dose, 48% v 35%; P = .048; medium-dose, 73% v 50%; P = .001) and failure rate (> 5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005). The 32-mg single dose was also superior to the 0.15 mg/kg times three dose regimen with regard to total number of emetic episodes (medium-dose, P = .033) and failure rate (high-dose, 20% v 36%; P = .009; medium-dose, 9% v 22%; P = .011). Ondansetron was well tolerated. The most common adverse event was headache. An approximate 10-fold increase in the incidence of clinically significant transaminase elevations was observed in the high-dose versus medium-dose cisplatin strata (aspartate aminotransferase [AST], 6.5% v 0.7%; serum alanine aminotransferase [ALT], 5.0% v 0.3%). CONCLUSION A 32-mg single dose of ondansetron is more effective than a single 8-mg dose and is at least as effective as the standard regimen of 0.15 mg/kg times three doses in the prevention of cisplatin-induced acute emesis.
Interferon alfa-2a and fluorouracil in the treatment of patients with advanced esophageal cancer.
Authors: Kelsen D , Lovett D , Wong J , Saltz L , Buckley M , Murray P , Heelan R , Lightdale C 
Published: February 2017

PURPOSE The trial was undertaken to determine the response rate to and toxicities from the combination of interferon alfa-2a (IFN) and fluorouracil (FU) in patients with advanced esophageal cancer. MATERIALS AND METHODS In this prospective phase II trial conducted at a large tertiary referral cancer center and university hospital, 40 patients with advanced locoregional, metastatic epidermoid, or adenocarcinoma of the esophagus were given FU 750 mg/m2 by 24-hour continuous intravenous infusion days 1 to 5, followed by weekly outpatient bolus FU 750 mg/m2 and IFN 9 x 10(6) U three times per week from day 1. Dose was attenuated for fatigue, neurotoxicity, gastrointestinal toxicity, and myelosuppression. RESULTS Complete and partial responses were seen in 10 of 37 assessable patients with esophageal cancer (27%; 95% confidence interval, 0.13 to 0.41). Although substantial, toxicity was tolerable and primarily involved fatigue and mild myelosuppression. The median duration of response was 6.4 months (range, 2.8 to 14+ months). CONCLUSION The combination of IFN and FU is an active regimen in the treatment of advanced esophageal cancer with a response rate similar to that reported for cisplatin-containing combinations in similar patient populations. Further studies based on this combination are indicated.
Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule.
Authors: Talcott J A , Siegel R D , Finberg R , Goldman L 
Published: February 2017

PURPOSE The study was undertaken to validate a clinical model for predicting the medical risk of cancer patients with fever and neutropenia. PATIENTS AND METHODS A consecutive sample of 444 cancer patients with fever and neutropenia (granulocyte count less than 500/microL) at two hospitals, a specialized cancer referral center and a university-affiliated general medical hospital, was studied to identify clinical characteristics in the first 24 hours that predict subsequent serious medical complications during the hospital stay. To control for bias, major risk factors and complications were subject to blinded review. RESULTS Serious medical complications occurred in 34% of patients with risk factors identified in a prior study, including prior inpatient status (group I), outpatients with a serious independent comorbidity (group II), or uncontrolled cancer (group III), compared with 5% of the remaining patients (group IV) (P less than .000001). Two of the complications in group IV patients were transient asymptomatic hypotension, and the remaining three complications occurred after at least 1 week of progressive medical deterioration. These risk groups were independently significant in stepwise logistic regression analysis. Multiple complications (17%) and death (10%) were common among patients in groups I through III but did not occur in group IV patients. CONCLUSIONS This risk assessment model accurately stratified the medical risk of these patients using only clinical information available on the first day of their course. Low-risk patients are an appropriate population in which to study less intensive treatment strategies.
Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients.
Authors: Clark G M , Mathieu M C , Owens M A , Dressler L G , Eudey L , Tormey D C , Osborne C K , Gilchrist K W , Mansour E G , Abeloff M D 
Published: February 2017

PURPOSE Formalin-fixed, paraffin-embedded tissues from axillary node-negative breast cancer patients were analyzed by flow cytometry to determine the prognostic significance of DNA ploidy and S-phase fraction (SPF). PATIENTS AND METHODS All patients were registered on a good-risk control arm of an intergroup clinical trial. They had small- to intermediate-sized (less than 3 cm), estrogen receptor (ER)-positive tumors and received no adjuvant therapy after modified radical mastectomy or total mastectomy with low axillary-node sampling. The median follow-up was 4.8 years. RESULTS Assessable ploidy results were obtained from 92% of the 298 specimens studied (51% diploid, 49% aneuploid), and SPFs were assessable for 83% of the tumors. SPFs for diploid tumors ranged from 0.7% to 11.9% (median, 3.6%), compared with a range of 1.2% to 26.7% (median, 7.6%) for aneuploid tumors (P less than .0001). No significant differences in disease-free or overall survival were observed between patients with diploid and aneuploid tumors. Using different SPF cutoffs by ploidy status (4.4% for diploid, 7.0% for aneuploid), patients with low SPFs had significantly longer disease-free survival rates than patients with high SPFs (P = .0008). The actuarial 5-year relapse rates were 15% and 32% for patients with low (n = 142) and high SPFs (n = 105), respectively. Similar relationships between SPF and clinical outcome were observed for patients with diploid tumors (P = .053) and for patients with aneuploid tumors (P = .0012). CONCLUSION S-phase fraction provides additional prognostic information for predicting disease-free survival for axillary node-negative breast cancer patients with small, ER-positive tumors.