bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical evaluation of MGI 209, an anesthetic, film-forming agent for relief from painful oral ulcers associated with chemotherapy.
Authors: LeVeque F G , Parzuchowski J B , Farinacci G C , Redding S W , Rodu B , Johnson J T , Ferretti G A , Eisenberg P D , Zimmer M B 
Published: February 2017

PURPOSE This open-label, multicenter trial evaluated the efficacy of a mucoadherent, anesthetic medication (MGI 209) for relief from painful oral ulcers associated with cytotoxic chemotherapy. PATIENTS AND METHODS Twenty-eight eligible cancer patients who had up to five discrete oral ulcers (total area < or = 5 cm2) completed this study. Mean age was 53.5 years (range, 21 to 81). Subjective assessments of oral discomfort before and after an orange juice pain challenge (OJPC), which was measured using a visual analog scale (VAS), and visual estimates of the amount of MGI 209 that remained on treated ulcers were collected at (1) baseline (before MGI 209 treatment); and (2) 30, 60, 120, and 180 minutes posttreatment. RESULTS Most subjects had low VAS scores (4 or less), which was indicative of oral discomfort, at baseline before and after the OJPC. At 30, 60, 120, and 180 minutes after MGI 209 treatment, most subjects had high VAS scores before and after an OJPC compared with baseline scores, which was indicative of a substantial increase in oral comfort; these differences were statistically significant (P < .0001). Mean percent of MGI 209 estimated to remain on ulcers at the previously mentioned times was 93.7%, 90.3%, 79.6%, and 71.3% of the total amount applied, respectively. CONCLUSION Benzocaine hydrochloride in combination with the protective, mucoadherent film-coating relieved discomfort for at least 3 hours even with exposure to an irritating beverage. MGI 209 treatment should allow patients with chemotherapy-induced oral ulcers to drink and eat with significantly diminished pain or no pain.
A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck.
Authors: Jacobs C , Lyman G , Velez-García E , Sridhar K S , Knight W , Hochster H , Goodnough L T , Mortimer J E , Einhorn L H , Schacter L 
Published: February 2017

PURPOSE To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer, we compared the efficacy and toxicity of cisplatin (CP) and fluorouracil (5-FU), alone and in combination in a phase III trial. PATIENTS AND METHODS Two hundred forty-nine patients with recurrent head and neck cancer were randomized to one of three treatments: CP (100 mg/m2) and 5-FU (1 g/m2 x 4), CP, or 5-FU every 3 weeks. RESULTS The overall response rate to the combination (32%) was superior to that of CP (17%) or 5-FU (13%) (P = .035). Response was associated with good performance status (PS) but not with primary site, site of recurrence, histology, prior irradiation, or relative dose intensity. Median time to progression was less than 2.5 months, and there was no significant difference in median survival (5.7 months) among the groups. By multivariate analysis, patients with better PS and poorly differentiated tumors had superior survival. Hematologic toxicity and alopecia were worse in the combination arm. CONCLUSION Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve.
Prolonged administration of oral etoposide in non-small-cell lung cancer: a phase II trial.
Authors: Waits T M , Johnson D H , Hainsworth J D , Hande K R , Thomas M , Greco F A 
Published: February 2017

PURPOSE The trial was undertaken to investigate the activity and toxicity of a prolonged schedule of oral etoposide in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Between March 1989 and August 1990, 25 patients with advanced NSCLC were treated with oral etoposide 50 mg/m2/d for 21 consecutive days, repeated every 28 to 35 days. The median patient age was 60 years (range, 38 to 84 years); male:female ratio was 12:13. Eight patients had stage IIIB disease; 17 had stage IV. Seventy-six percent of patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. No patient had received previous chemotherapy with standard agents; nine patients had received previous or concurrent radiation therapy. Plasma etoposide concentrations were measured to estimate etoposide bioavailability and kinetics. RESULTS Five of 22 patients (23%; 95% confidence interval [CI], 10% to 43%) had partial responses. Median response duration was 5 months (range, 2 to 6 months). Four of five responders were female. Besides alopecia, which occurred in all patients, myelosuppression was the most common toxicity, but was mild or moderate in most patients. Median leukocyte nadir during course 1 was 3,200/microL; only four of 69 courses produced a leukocyte nadir less than 1,000/microL. Severe thrombocythemia (less than 75,000/microL) did not occur. Gastrointestinal toxicity was uncommon. Median peak etoposide concentration was 3.4 micrograms/mL. A mean serum etoposide concentration greater than 1 microgram/L was maintained for more than 13 hours; the plasma concentration-time curve (AUC) was estimated to be 90% of that predicted after an identical dose of etoposide given intravenously. CONCLUSIONS Etoposide given by this dose and schedule has moderate activity as first-line systemic therapy for advanced NSCLC. In previously untreated patients, chronic oral etoposide is well tolerated, and incorporation into combination regimens should be feasible. Etoposide bioavailability may be increased at lower oral doses.
Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials.
Authors: Gregory W M , Richards M A , Malpas J S 
Published: February 2017

PURPOSE A meta-analysis was performed to compare survival after treatment with melphalan and prednisolone (M + P) with that after combination chemotherapy (CCT) in patients with multiple myeloma. METHODS Meta-analysis was performed on 18 published trials comprising 3,814 patients comparing M + P with CCT. Two-year survival percentages with observed and expected deaths at 2 years were calculated for each trial, and the overview methodology was applied to these figures. RESULTS Overall results from the 18 trials suggest that there is no difference in efficacy between the two treatments. This finding, however, masks a highly significant correlation between 2-year survival rates for M + P-treated patients in individual studies and the difference between the M + P and CCT 2-year survival rates for that study (r = .69; P = .0008). In separate overviews, those studies with a high M + P 2-year survival rate showed a survival difference in favor of M + P (P = .02), whereas those with a low rate suggested a difference in favor of CCT (P V .07). Comparison of the 2-year survival rates in the M + P treatment arms of each of the studies with available data showed an inverse correlation between survival and the proportion of patients with either poor performance status (P less than .001) or immunoglobulin A (IgA) M band (P = .02). CONCLUSIONS These results imply that M + P is superior for patients with an intrinsically good prognosis and inferior for those patients with a poor prognosis. If reliable prognostic factors can be established for this disease, they could be used to select therapy for individual patients.
Molecular and immunophenotypic characterization of AIDS-associated, Epstein-Barr virus-negative, polyclonal lymphoma.
Authors: Shiramizu B , Herndier B , Meeker T , Kaplan L , McGrath M 
Published: February 2017

PURPOSE A molecular analysis of non-Hodgkin's lymphomas (NHLs) from patients with AIDS was undertaken to determine the prevalence and immunophenotype of polyclonal B-cell lymphoma. MATERIALS AND METHODS DNA was extracted from 40 diagnostic biopsy specimens obtained from patients seen at University of California, San Francisco (UCSF) between 1986 and 1990. Clonality, infection with Epstein-Barr virus (EBV), and presence of a rearranged c-myc gene were determined by Southern blot analysis. Lymphoma immunophenotypes were determined by frozen-section immunohistochemical analysis. RESULTS The most prevalent genotype of lymphoma in this study was that of polyclonal, EBV-negative tumors with no evidence of c-myc rearrangement (14 of 40; 35%). Monoclonal, EBV-positive tumors with no evidence of c-myc rearrangement comprised the second most prevalent class (10 of 40; 25%), and polyclonal, EBV-positive tumors similar to those seen in transplant patients were observed in only a small subset (three of 40; 8%) of specimens analyzed. The immunophenotype of B cells in the polyclonal EBV-negative subset was equally divided into B-cell-predominant and mixed-phenotype lymphomas, with the latter category containing numerous infiltrating T cells. The B cells in each category were immunoglobulin M-positive (IgM+), CD20+, CD21-. All but one of the polyclonal NHLs had large-cell histology. CONCLUSIONS EBV-negative, AIDS-associated, polyclonal B-cell lymphoma appears to be a new class of human immunodeficiency virus (HIV)-associated disease more prevalent in the current study than any other molecular subclass. The absence of CD21, the EBV receptor, may explain in part the absence of EBV within this polyclonal B-cell population.
Acquired von Willebrand disease in Wilms' tumor patients.
Authors: Coppes M J , Zandvoort S W , Sparling C R , Poon A O , Weitzman S , Blanchette V S 
Published: February 2017

PURPOSE A prospective study was performed to determine the incidence of acquired von Willebrand disease (vWD) in children with newly diagnosed Wilms' tumor. PATIENTS AND METHODS Fifty consecutive children with newly diagnosed Wilms' tumor were evaluated. Detailed family and bleeding histories were obtained in all cases. Laboratory evaluation included measurement of the circulating platelet count, bleeding time (BT), factor VIII (FVIII) and von Willebrand factor (vWF) levels, and ristocetin cofactor (RCoF) activity. A vWF multimer analysis was obtained in all cases in which vWD was suspected. RESULTS Four of 50 (8%) consecutive children with a diagnosis of Wilms' tumor were found to have acquired vWD. Laboratory findings indicated type III vWD in two patients and type I vWD in the other two. CONCLUSIONS The incidence of acquired vWD in association with Wilms' tumor merits further study through a large prospective trial. Such a trial should include careful family and clinical bleeding histories plus measurement of a platelet count, BT, coagulant FVIII and vWF levels, RCoF activity, and vWF multimer analysis. The response to 1-desamino-8-D-arginine vasopressin (DDAVP) should be tested in all patients with Wilms' tumor and acquired vWD, including patients with a type III profile, before an invasive procedure is performed. Successful use of DDAVP may avoid exposure of affected patients to blood products.
FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer.
Authors: Kelsen D , Atiq O T , Saltz L , Niedzwiecki D , Ginn D , Chapman D , Heelan R , Lightdale C , Vinciguerra V , Brennan M 
Published: February 2017

PURPOSE The chemotherapy regimens of high-dose methotrexate, high-dose fluorouracil (FU), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and leucovorin (FAMTX) and etoposide, Adriamycin, and cisplatin (EAP) have both been reported in nonrandom assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer, as well as major toxicities of myelosuppression. Here we report a prospective, stratified, random-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer. PATIENTS AND METHODS Sixty patients were entered onto the trial, 30 receiving EAP and 30 FAMTX. All patients had measurable or assessable tumor masses. Patient entry was stopped at the point when significant toxicity differences were seen at interim analysis. RESULTS Response rates were similar between the two arms (FAMTX, 33% [95% confidence interval (CI), 16% to 50%]; EAP, 20% [95% Cl, 6% to 34%]). Three FAMTX and no EAP patients had complete remissions. The median survival for the two arms were similar (EAP, 6.1 months; FAMTX, 7.3 months). At 1 year, 7% of EAP and 17% of FAMTX patients were alive. EAP caused significantly more myelosuppression (leukopenia, P = .002; anemia, P = .03; thrombocytopenia, P = .0001) than did FAMTX. EAP also resulted in significantly longer hospitalizations per study month (8 v 5 days). Four EAP patients died of lethal toxicity, whereas no FAMTX patients died of treatment-related causes (P = .04). CONCLUSIONS FAMTX is at least as active as EAP and is significantly less toxic. Although both regimens remain investigational, the toxicities of FAMTX are more manageable. Further studies involving FAMTX in both the adjuvant and advanced disease setting are underway.
Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage III unresectable non-small-cell lung cancer: results of the Toronto Phase II Trial.
Authors: Burkes R L , Ginsberg R J , Shepherd F A , Blackstein M E , Goldberg M E , Waters P F , Patterson G A , Todd T , Pearson F G , Cooper J D 
Published: February 2017

PURPOSE The 5-year survival rates with surgical resection for preoperatively identified stage IIIA N2 non-small-cell lung cancer (NSCLC) are less than 10%. A pilot study of mitomycin, vindesine, and cisplatin (MVP) induction chemotherapy was undertaken in an attempt to improve the curative potential of surgery in this group of patients. PATIENTS AND METHODS Thirty-nine patients with mediastinoscopy stage IIIA N2 NSCLC received two cycles of MVP. Responding patients underwent thoracotomy for resection and two further courses of MVP. RESULTS The overall response rate was 64% (25 of 39) with three complete and 22 partial responses. Twenty-two patients were resected, which included a radical mediastinal node dissection. Eighteen resections were complete and four were incomplete. Pathologically, three patients (7.7%) had no tumor remaining. Toxicity included two postoperative deaths secondary to a bronchopleural (BP) fistula, mitomycin pulmonary toxicity in two patients, and septic deaths in four patients. Twenty-eight patients have died; 20 have recurrent or progressive disease. Eight of the 18 patients completely resected have recurred, with a median time to recurrence of 20.6 months. Sites of recurrence include two locoregional, five distant (two in brain), and one in both. Median survival of all 39 patients is 18.6 months, with a 3-year survival of 26%. The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40%. CONCLUSIONS We conclude (1) that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC; (2) the median survival seems to be prolonged; and (3) the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a phase III randomized trial to compare it with other treatment modalities.
Combined modality therapy for primary CNS lymphoma.
Authors: DeAngelis L M , Yahalom J , Thaler H T , Kher U 
Published: February 2017

PURPOSE Primary CNS lymphoma (PCNSL), formerly rare, is being seen with increased frequency among apparently immunocompetent patients. Conventional treatment has consisted of whole-brain radiotherapy (RT) and corticosteroids, with a median survival of 15 to 18 months and a 3% to 4% 5-year survival. Chemotherapy has been useful in the treatment of recurrent PCNSL. In 1985 we began a treatment protocol using chemotherapy and cranial irradiation for the initial therapy of non-AIDS PCNSL. PATIENTS AND METHODS Thirty-one patients (group A) completed the combined modality regimen. All had placement of an Ommaya reservoir and received pre-RT systemic methotrexate, 1 g/m2, plus six doses of intra-Ommaya methotrexate at 12 mg per dose. A full course of cranial RT (4,000-cGy whole-brain RT plus a 1,440-cGy boost) was followed by two cycles of high-dose cytarabine (ara-C), with each course consisting of two doses of 3 g/m2 ara-C separated by 24 hours and infused over 3 hours. During this period, 16 additional patients (group R) were treated with RT alone, either because patients refused chemotherapy or RT was initiated before our consultation; all would have been eligible to participate in the protocol. Follow-up extended through April 1, 1991. RESULTS Group A had a significantly prolonged time to recurrence (median, 41 months) compared with group R (median, 10 months; P = .003). Although median survival was doubled from 21.7 months for group R to 42.5 months for group A, this was not statistically significant because of small sample size. More importantly, group R patients received systemic chemotherapy for recurrent PCNSL, which improved survival. CONCLUSION The addition of chemotherapy to cranial RT for initial treatment of PCNSL significantly improved disease-free survival and contributed to overall survival; all non-AIDS patients with newly diagnosed PCNSL should be considered for combined modality therapy.
Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission.
Authors: Verdonck L F , Dekker A W , de Gast G C , Lokhorst H M , Nieuwenhuis H K 
Published: February 2017

PURPOSE Adult patients with poor-risk lymphoblastic lymphoma (LBL) treated with intensive multiagent chemotherapy (acute lymphoblastic leukemia [ALL]-like regimens) have a poor prognosis, with a disease-free long-term survival rate of less than 20%, caused by a very high relapse rate. Thus, adult patients with poor-risk LBL are candidates for alternative intensive consolidation therapy. PATIENTS AND METHODS Nine adult patients with poor-risk LBL in first remission after treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; six patients) or ALL-like regimens (three patients), were treated with high-dose cyclophosphamide and total body irradiation (TBI) followed by nonpurged autologous bone marrow transplantation (ABMT). RESULTS Two of nine patients relapsed at 4 and 8 months, respectively, after BMT, and one patient died of acute myeloblastic leukemia (AML) 7 months after ABMT without recurrence of his lymphoma. Six patients are in unmaintained first remission with a follow-up of 12 to 113 months (median, 53 months) after transplantation. CONCLUSIONS These results suggest that intensive consolidation therapy with high-dose cyclophosphamide and TBI followed by nonpurged ABMT may improve the long-term prognosis of this disease.
Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor.
Authors: Rowinsky E K , Grochow L B , Hendricks C B , Ettinger D S , Forastiere A A , Hurowitz L A , McGuire W P , Sartorius S E , Lubejko B G , Kaufmann S H 
Published: February 2017

PURPOSE A phase I and pharmacologic study was undertaken to determine the maximum-tolerated dose (MTD), describe the principal toxicities, and characterize the pharmacologic behavior of topotecan, which is a semisynthetic analog of camptothecin with broad preclinical antitumor activity and the first topoisomerase I-targeting agent to enter clinical development in the United States since studies of sodium camptothecin over 2 decades ago. PATIENTS AND METHODS Thirty-minute infusions of topotecan were administered daily for 5 consecutive days every 3 weeks to patients with advanced solid malignancies at doses ranging from 0.5 to 2.5 mg/m2/d. RESULTS At doses of 1.5 and 2.0 mg/m2, grade 3 and 4 neutropenia occurred in most courses; however, neutropenia was brief and rarely associated with fevers or treatment delays. Neutropenia was more severe in patients with extensive prior treatment than in minimally pretreated patients, but these differences were not substantial. At 2.5 mg/m2, topotecan induced profound and prolonged neutropenia that was frequently associated with fever and treatment delays in minimally pretreated patients. Topotecan also induced mild depressions in the hematocrit level in the majority of courses; however, precipitous drops requiring transfusional therapy occurred in 14% of courses and suggested a drug-induced hemolytic effect. Unlike sodium camptothecin, hemorrhagic cystitis was not observed. Thrombocytopenia, skin rash, diarrhea, and vomiting occurred infrequently and were modest in severity. Responses were observed in non-small-cell lung carcinoma and platinum-refractory ovarian carcinoma. Drug disposition in plasma was described by a biexponential model, with renal elimination accounting for 38.7% of drug disposition. Topotecan was rapidly hydrolyzed in vivo to a less active, open-ring form. CONCLUSIONS Neutropenia is the dose-limiting toxicity, and 1.5 mg/m2 is the recommended starting dose of topotecan for both minimally and heavily pretreated patients in future phase II trials, with escalation to 2.0 mg/m2 if treatment is well tolerated. Non-small-cell lung and platinum-refractory ovarian carcinomas should be among those evaluated in phase II trials of topotecan.
Factors predicting treatment responsiveness and prognosis in node-negative breast cancer. The International (Ludwig) Breast Cancer Study Group.
Authors: Neville A M , Bettelheim R , Gelber R D , Säve-Söderbergh J , Davis B W , Reed R , Torhorst J , Golouh R , Peterson H F , Price K N 
Published: February 2017

PURPOSE An international trial (formerly Ludwig Trial V) has been conducted in 1,275 subjects to ascertain if perioperative chemotherapy is beneficial for node-negative breast cancer patients and to identify subgroups of patients who benefit from this therapy. PATIENTS AND METHODS Node-negative breast cancer patients were randomized to receive either one cycle of perioperative chemotherapy or no adjuvant treatment. A detailed pathology review was conducted in 1,203 of the 1,275 patients enrolled. Stepwise Cox regression analysis was used to search for factors either predicting chemotherapeutic responsiveness and/or influencing disease-free survival (DFS). RESULTS As expected, primary tumor size, grade, and the presence of peritumoral vascular invasion are the most important prognostic factors. Perioperative chemotherapy provides a DFS advantage at 5 years of median follow-up and such treatment is more effective for estrogen receptor-negative than for estrogen receptor-positive tumors, for histologic grade 2 and 3 than for grade 1 tumors, and for patients in whom no axillary lymph node metastases were found even after serial sectioning and review by the Central Pathology Laboratory. CONCLUSION Hormone receptor status and tumor grade are important factors for predicting responsiveness to perioperative chemotherapy in node-negative breast cancer.