bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer.
Authors: Gause B L , Sznol M , Kopp W C , Janik J E , Smith J W , Steis R G , Urba W J , Sharfman W , Fenton R G , Creekmore S P , Holmlund J , Conlon K C , VanderMolen L A , Longo D L 
Published: February 2017

PURPOSE Although high-dose interleukin-2 (IL-2) can produce durable remissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity. The purpose of this study is to define the maximum-tolerated dosage (MTD) of IL-2 and interferon alfa-2a (IFN alpha-2a) that can be administered chronically on an outpatient basis. PATIENTS AND METHODS Fifty-three patients with advanced cancer of variable histology with good prognostic features were treated in six cohorts. Patients in cohorts one through five received IL-2 (1.5 or 3.0 x 10(6) million units (mU)/m2) Monday through Friday and IFN alpha-2a (1.5 or 3 x 10(6) mU/m2) daily for a 4-week cycle. In cohort six, IFN alpha-2a was given three times a week. Immunologic monitoring, including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (NK) activity, were measured. Patients were evaluated for toxicity, response, and survival. RESULTS Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were most severe with the first treatment of each week. Dose-limiting toxicities included grade III fatigue, hypotension, and creatinine elevations. The MTD was 1.5 mU/m2 daily x 5 given subcutaneously repeated weekly for IL-2 and 1.5 mU/m2 daily subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with RCC (24%) achieved a partial response (PR), including four of eight patients who were previously untreated. There were no objective responses in patients with other tumors, including 12 melanoma patients. CONCLUSION IL-2 and IFN alpha-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC.
Lymph node retrieval in a randomized trial on western-type versus Japanese-type surgery in gastric cancer.
Authors: Bunt A M , Hermans J , van de Velde C J , Sasako M , Hoefsloot F A , Fleuren G , Bruijn J A 
Published: February 2017

PURPOSE In the tumor-node-metastasis (TNM) staging system, no recommendations are provided on what lymph node retrieval technique is to be used to determine lymph node status, which leads to variability in nodal status assessment and TNM staging. PATIENT AND METHODS Lymph node retrieval was quantitated using data from 237 curatively resected gastric cancer patients, from a prospective, randomized trial that compared the Western resection with limited (D1) and the Japanese resection with extended lymphadenectomy (D2), and compared data from the literature. Moreover, the efficacy of different lymph node retrieval techniques was determined. RESULTS The mean yield of lymph nodes was 15 in D1 and 30 in D2, which is similar to results from German investigators, but substantially lower than results from Japanese investigators (60 in D2). Use of a fat-clearance technique significantly increased (P = .01) nodal yields compared with conventional retrieval. Significantly higher yields (P < .001) were obtained by a Japanese surgeon using conventional retrieval directly postoperatively. Experience of surgicopathologic teams with processing resection specimens did not influence nodal yields. Further analysis showed that reference values for nodal yields per anatomically defined station as reported in the literature were contradicted by our results and indicated the ambiguity of such standards. CONCLUSION Despite some anatomical variability in the distribution of lymph nodes, advice on the number of nodes to examine per N level, feasible in all patients, should be incorporated into the TNM classification to standardize nodal status assessment. Based on our findings, we advocate retrieval of nodes immediately postoperatively by the surgeon.
Determinants of postchemotherapy nausea and vomiting in patients with cancer. Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group.
Authors: Osoba D , Zee B , Pater J , Warr D , Latreille J , Kaizer L 
Published: February 2017

PURPOSE To assess whether prechemotherapy health-related quality-of-life (HQL) variables are associated with postchemotherapy nausea and vomiting (PCNV), and to determine their relationship to patient and treatment variables. PATIENTS AND METHODS Eight hundred thirty-two chemotherapy-naive patients scheduled to receive antiemetic regimens containing a 5-hydroxytryptamine (5-HT3) antagonist with or without dexamethasone for moderately or highly emetogenic chemotherapy were enrolled. HQL was measured by the self-report European Organization for Research and Treatment of Cancer (EORTC) Care Quality of Life Questionnaire (QLQ-C30) within 7 days before chemotherapy. Prechemotherapy HQL scores, as well as other patient, disease, and treatment variables were compared in the groups of patients who had PCNV and those who did not have PCNV. All variables were assessed initially in a univariate analysis and then together in a multivariate analysis using step-wise logistic regression. The final model generated by the multivariate analyses was used in a risk factor analysis to predict PCNV. RESULTS Univariate analyses identified 10 HQL variables and five patient and treatment characteristics that were associated with PCNV. In the multivariate analysis, the variables remaining in the final model included low social functioning, prechemotherapy nausea, female gender, highly emetogenic chemotherapy, and the lack of maintenance antiemetics (5-HT3 antagonists with or without dexamethasone) after chemotherapy. A history of low alcohol use was also associated with PCV, whereas increased fatigue and lower performance status were associated with PCN. In the risk factor analysis, the incidence of PCV increased from 20% in those having no risk factors to 76% in those having any four of the six risk factors. CONCLUSION Several pretreatment HQL, patient, and treatment characteristics are associated with the occurrence of PCNV. Patients about to receive moderately or highly emetogenic chemotherapy should be screened for these factors and additional measures, such as behavior modification and modification of antiemetic therapy, should be considered in attempts to improve the control of PCNV.
IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma.
Authors: Maloney D G , Grillo-López A J , Bodkin D J , White C A , Liles T M , Royston I , Varns C , Rosenberg J , Levy R 
Published: February 2017

PURPOSE To evaluate the safety, pharmacokinetics, and biologic effect of multiple doses of the chimeric anti-CD20 monoclonal antibody (mAb) IDEC-C2B8 in patients with relapsed B-cell lymphoma. PATIENTS AND METHODS Twenty patients with relapsed low-grade (n = 15) or intermediate-/high-grade (n = 5) lymphoma received weekly infusions times four of 125 mg/m2 (n = 3), 250 mg/m2 (n = 7), or 375 mg/m2 (n = 10) of IDEC-C2B8. RESULTS Infusional side effects during the initial infusion were mainly grade I/II fever, asthenia, chills, nausea, rash, and urticaria. More serious events were rare. Peripheral-blood B cells were rapidly depleted and slowly recovered over 3 to 6 months. There was no change in mean immunoglobulin (Ig) levels. Antibody serum half-life (and maximum concentration [Cmax]) generally increased between the first and fourth infusions (33.2 hours v 76.6 hours, respectively) following the 375-mg/m2 doses. Six of 18 assessable patients had a partial remission (PR), with a median time to disease progression of 6.4 months (range, 3 to 21.7). Minor responses (MRs) were observed in five patients and progressive disease (PD) in seven. Tumor responses occurred in peripheral blood, bone marrow (BM), spleen, bulky lymph nodes, and extranodal sites, and in patients who had relapsed following high-dose myeloablative chemotherapy. Six of 14 patients (40%) with a low-grade histology responded. Four of six with bulky disease had a PR. CONCLUSION IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma. The 375-mg/m2 dose has been selected for a phase II trial in patients with relapsed low-grade or follicular B-cell lymphoma.
Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies.
Authors: Ippoliti C , Champlin R , Bugazia N , Przepiorka D , Neumann J , Giralt S , Khouri I , Gajewski J 
Published: February 2017

PURPOSE Diarrhea associated with acute gastrointestinal (GI) graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) can result in severe morbidity and mortality. A pilot study was conducted to evaluate the efficacy and toxicity of octreotide in the management of diarrhea in patients with GVHD after allogeneic BMT. PATIENTS AND METHODS Twenty-one patients entered the study. Patients received either peripheral-blood stem cells (n = 13) or bone marrow (n = 8). Seven patients had grade 4, 13 grade 3, and one grade 2 GVHD. Intravenous (I.V.) octreotide 500 microg every 8 hours for 7 days was administered. Octreotide treatment was discontinued if no response was observed after 7 days or for grade 4 toxicity. RESULTS Fifteen (71%) of 21 treated patients had a complete response within 7 days of the initiation of octreotide; three (14%) had a partial response and three (14%) failed to respond to treatment. Toxicities were minimal; hyperglycemia was seen in four patients and one patient developed a partial ileus. Octreotide was discontinued and the ileus resolved within 48 hours. CONCLUSION If initiated early in the course of GI GVHD, octreotide appears to be an effective, well-tolerated agent in reducing severe voluminous diarrhea. Octreotide should be discontinued within 24 hours after the resolution of diarrhea to avoid the development of ileus. Because no additional reduction in the volume of diarrhea occurred after 7 days of therapy, continuation of the drug beyond this time is not cost effective.
Paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of small-cell lung cancer: comparison of sequential phase II trials using different dose-intensities.
Authors: Hainsworth J D , Gray J R , Stroup S L , Kalman L A , Patten J E , Hopkins L G , Thomas M , Greco F A 
Published: February 2017

PURPOSE In two sequential phase II studies, we evaluate the feasibility and efficacy of adding paclitaxel to a standard platinum/etoposide regimen in the first-line treatment of small-cell lung cancer. PATIENTS AND METHODS One hundred seventeen patients with small-cell lung cancer were treated between June 1993 and July 1996. The first 38 patients received a lower-dose regimen: paclitaxel 135 mg/m2 by 1-hour infusion, carboplatin at an area under the concentration-time curve (AUC) of 5.0, and etoposide 50 mg alternating with 100 mg orally on days 1 to 10. When only mild myelosuppression was observed, doses of paclitaxel and carboplatin were increased in the subsequent 79 patients (paclitaxel 200 mg/m2 by 1-hour infusion and carboplatin at an AUC of 6.0). All patients received four courses of treatment, administered at 21-day intervals. Patients with limited-stage small-cell lung cancer also received thoracic radiation therapy (1.8 Gy/d; total dose, 45 Gy) administered concurrently with courses 3 and 4 of chemotherapy. RESULTS Seventy-two of 79 patients (91%) who receive the higher-dose regimen had major responses. Thirty-two of 38 (84%) with extensive-stage disease responded (21% complete response rate); median survival was 10 months for this group. With limited-stage disease, the overall response rate was 98%, with 71% complete responses; the median survival time has not been reached at 16 months. Median survival in extensive-stage patients was longer in patients who received the higher-dose regimen (10 months) than in the previous group treated with lower doses (7 months; P = .008). The higher-dose regimen was well tolerated, with myelosuppression being the major toxicity. Compared with the lower-dose regimen, grade 3/4 neutropenia increased from 8% to 38% of courses, but the incidence of hospitalization for neutropenia and fever did not increase. Other nonhematologic toxicities were uncommon, and did not increase substantially with the higher-dose regimen. CONCLUSION Paclitaxel can be added at full dose (200 mg/m2) to a carboplatin/etoposide combination while maintaining a tolerable toxicity profile. Median survival times in both extensive- and limited-stage patients compare favorably with other reported regimens. This regimen merits further investigation, and a randomized trial to compare this regimen with a standard carboplatin/etoposide combination is underway.
Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients.
Authors: Warzocha K , Salles G , Bienvenu J , Bastion Y , Dumontet C , Renard N , Neidhardt-Berard E M , Coiffier B 
Published: February 2017

PURPOSE A prospective study was performed to assess plasma measurement of tumor necrosis factor (TNF), lymphotoxin alpha (LTalpha), and their soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas. PATIENTS AND METHODS One hundred forty-two patients, 124 with non-Hodgkin's lymphoma (NHL) and 18 with Hodgkin's disease (HD), were analyzed. Plasma samples were tested by enzyme-linked immunoabsorbent assay (ELISA). RESULTS Elevated plasma levels of TNF, p55,and p75 were associated with an Eastern Cooperative Oncology Group (ECOG) status > or = 2, Ann Arbor stage III/IV, elevated serum lactate dehydrogenase (LDH) and beta2-microglobulin levels, > or = two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p55 and p75 were associated with older age and higher values of C-reactive protein. TNF, p55, and p75, but not LTalpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome were identified: patients with low risk (TNF, p55, and p75 below median values), intermediate risk (one or two parameters higher than median), and high risk (all three parameters higher than median). At a median follow-up duration of 25 months, the actuarial 2-year FFP survival rates were 79%, 60%, and 37%, respectively (P < .0001), and overall survival rates were 91%, 82%, and 51% (P < .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IPI) yielded a significant improvement of the predictive value of IPI. CONCLUSION TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.
Progenitor-cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor-cell quantity and quality and factors predicting for these parameters in 101 pretreated patients with malignant lymphoma.
Authors: Watts M J , Sullivan A M , Jamieson E , Pearce R , Fielding A , Devereux S , Goldstone A H , Linch D C 
Published: February 2017

PURPOSE To define parameters that predict for rapid engraftment after peripheral-blood stem-cell (PBSC) transplantation, progenitor thresholds, the proportion of patients who achieve these thresholds with a standardized mobilization regimen, and the factors that predict for mobilization efficiency. PATIENTS AND METHODS One hundred and one patients with pretreated lymphoma were mobilized with cyclophosphamide 1.5 g/m2 and granulocyte colony-stimulating factor (G-CSF), with the first apheresis performed when the recovery WBC count was > or = 5.0 x 10(9)/L. The relationship between the number of progenitor cells collected and patient age, sex, diagnosis, prior radiotherapy, and time since last chemotherapy was determined by multivariate analysis. The relationship between these factors, progenitor numbers returned, post-PBSC G-CSF, and hematologic recovery was performed in 81 patients following chemotherapy with carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM protocol). RESULTS No BEAM recipients had delayed neutrophil recovery beyond 28 days. Delayed platelet recovery occurred in 7.4% and minimum and optimum thresholds of 1 x 10(6) and 3.5 x 10(6) CD34+ cells/kg and 1 x 10(5) and 3.5 x 10(5) granulocyte-macrophage colony-forming cells (GM-CFC)/kg were established. Hematologic recovery was adversely affected by prior treatment with mini-BEAM, and neutrophil recovery was accelerated by post-PBSC G-CSF. The minimum GM-CFC threshold was achieved with a single apheresis in 83% of patients and in 90% with two aphereses. The optimal threshold was achieved with two leukaphereses in 69% of patients. Prior radiotherapy adversely affected mobilization. CONCLUSION Hematopoietic recovery following PBSC is dependent on progenitor-cell number infused and affect of previous chemotherapy on progenitor quality. Progenitor-cell mobilization is adversely affected by prior radiotherapy. The minimum threshold of GM-CFC required is achieved in most patients with a single apheresis, but an optimal collection usually requires at least two harvests.
Comparison of psychologic outcome in adult survivors of childhood acute lymphoblastic leukemia versus sibling controls: a cooperative Children's Cancer Group and National Institutes of Health study.
Authors: Zeltzer L K , Chen E , Weiss R , Guo M D , Robison L L , Meadows A T , Mills J L , Nicholson H S , Byrne J 
Published: February 2017

PURPOSE To determine psychologic outcome, with the focus on emotional or mood state, of young adult survivors of childhood acute lymphoblastic leukemia (ALL) compared with sibling controls and to identify vulnerable subgroups at highest risk for negative mood. PATIENTS AND METHODS Adult survivors (n = 580), aged > or = 18 years, who were treated before age 20 years on Children's Cancer Group (CCG) protocols for ALL and 396 sibling controls were administered a structured telephone interview and the Profile of Moods State (POMS), a standardized measure of affective state. RESULTS Survivors had higher total mood scores (which indicates greater negative mood) than sibling controls (P<.01) and reported more tension (P< .01), depression (P<.01), anger (P<.01), and confusion (P<.01), but not more fatigue or less vigor. Female, minority, and unemployed survivors reported the highest total mood disturbance. Overall, survivors were more likely to be unemployed (P<.05) or working less than half-time (P<.01) compared with controls. CONCLUSION This large, sibling-controlled, multisite study of young adult survivors of childhood ALL treated on CCG protocols after 1970 found significant increased negative mood in survivors, not accounted for by reported energy level differences, which suggests that these emotional effects are not likely the result of current illness. Survivors are less likely to be fully employed. Female, minority, and unemployed survivors are at greatest risk for emotional sequelae, a finding that indicates the need for targeted, preventive intervention.
Unrelated donor bone marrow transplantation for children with acute leukemia.
Authors: Davies S M , Wagner J E , Shu X O , Blazar B R , Katsanis E , Orchard P J , Kersey J H , Dusenbery K E , Weisdorf D J , McGlave P B , Ramsay N K 
Published: February 2017

PURPOSE To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias. PATIENTS AND METHODS Between June 1985 and December 1994, 50 children with acute leukemia (15 acute myelogenous leukemia [AML], 35 acute lymphoblastic leukemia [ALL]; 22 greater than second complete remission [CR]) received BMT from a URD at the University of Minnesota. Ages ranged from 0.9 to 17.5 years (median, 8.8). Median follow-up is 2.1 years (range, 1 to 7.3). Thirty patients (60%) received bone marrow fully matched at HLA-A,B and DRB1; 20 (40%) received bone marrow with a major or minor mismatch at a single HLA-A or B locus. RESULTS The median time to neutrophil engraftment was day 24 (range, 14 to 42 days) in those receiving matched and day 25 (range, 15 to 32 days) in those receiving mismatched marrow (P = .35). The incidence of grades III to IV graft-versus-host disease (GVHD) was 23% (95% confidence interval [CI], 7% to 39%) in matched and 32% (95% CI, 8% to 52%) in HLA-mismatched patients (P = .57). The incidence of chronic GVHD was 50% (95% CI, 28% to 72%) in matched and 57% (95% CI, 23% to 91%) in mismatched patients (P = .80). Disease-free survival for patients with ALL is 37% (95% CI, 21% to 53%) at 1 year and 30% (95% CI, 15% to 46%) at 2 years; for patients with AML, 53% (95% CI, 28% to 78%) at 1 year and 33% (95% CI, 6% to 60%) at 2 years. CONCLUSION URD BMT is an effective treatment for children with poor-prognosis acute leukemia and should be considered for all high-risk patients. Early referral of patients is strongly recommended.
Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.
Authors: Lacava J A , Leone B A , Machiavelli M , Romero A O , Perez J E , Elem Y L , Ferreyra R , Focaccia G , Suttora G , Salvadori M A , Cuevas M A , Acuña L R , Acuña J R , Langhi M , Amato S , Castaldi J , Arroyo A , Vallejo C T 
Published: February 2017

PURPOSE To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). PATIENTS AND METHODS Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. RESULTS One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. CONCLUSION VNB is an active drug against ACC with moderate toxicity. Its activity is among the highest reported for single agents. Further evaluation in association with other agents is clearly justified.