bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pivotal Phase III Trial of Two Dose Levels of Denileukin Diftitox for the Treatment of Cutaneous T-Cell Lymphoma
Authors: Olsen Elise , Duvic Madeleine , Frankel Arthur , Kim Youn , Martin Ann , Vonderheid Eric , Jegasothy Brian , Wood Gary , Gordon Michael , Heald Peter , Oseroff Allan , Pinter-Brown Lauren , Bowen Glen , Kuzel Timothy , Fivenson David , Foss Francine , Glode Michael , Molina Arturo , Knobler Elizabeth , Stewart Stanford , Cooper Kevin , Stevens Seth , Craig Fiona , Reuben James , Bacha Patricia , Nichols Jean 
Published: February 2017

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Phar-maceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on ≥ 20% of lymphocytes were assigned to one of two dose levels (9 or 18 μg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti–interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 μg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.
Prognostic Value of Positron Emission Tomography (PET) With Fluorine-18 Fluorodeoxyglucose ([18F]FDG) After First-Line Chemotherapy in Non-Hodgkin’s Lymphoma: Is [18F]FDG-PET a Valid Alternative to Conventional Diagnostic Methods?
Authors: Spaepen Karoline , Stroobants Sigrid , Dupont Patrick , Van Steenweghen Steven , Thomas José , Vandenberghe Peter , Vanuytsel Lucien , Bormans Guy , Balzarini Jan , De Wolf-Peeters Christine , Mortelmans Luc , Verhoef Gregor 
Published: February 2017

PURPOSE: A complete remission (CR) after first-line therapy is associated with longer progression-free survival (PFS). However, defining CR is not always easy because of the presence of residual masses. Metabolic imaging with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) offers the ability to differentiate between viable and fibrotic inactive tissue. In this study, we evaluated the value of PET in detecting residual disease and, hence, predicting relapse after first-line treatment in patients with non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Ninety-three patients with histologically proven NHL, who underwent a whole-body [18F]FDG-PET study after completion of first-line chemotherapy and who had follow-up of at least 1 year, were included. Persistence or absence of residual disease on PET was related to PFS using Kaplan-Meier survival analysis. RESULTS: Sixty-seven patients showed a normal PET scan after first-line chemotherapy; 56 of 67 remained in CR, with a median follow-up of 653 days. Nine of these patients with a residual mass considered as unconfirmed CR received additional radiotherapy. Only 11 of 67 patients relapsed (median PFS, 404 days). Persistent abnormal [18F]FDG uptake was seen in 26 patients, and all of them relapsed (median PFS, 73 days). Because standard restaging also suggested residual disease, 12 patients received immediate secondary treatment. In 14 of 26 patients, only PET predicted persistent disease. From these patients, relapse was proven either by biopsy (n = 8) or by progressive disease on computed tomography or magnetic resonance imaging (n = 6). CONCLUSION: Persistent abnormal [18F]FDG uptake after first-line chemotherapy in NHL is highly predictive for residual or recurrent disease. In relapsing patients, PFS was significantly shorter after a positive scan than after a negative scan.
Frequency of the Bcl-2/IgH Rearrangement in Normal Individuals: Implications for the Monitoring of Disease in Patients With Follicular Lymphoma
Authors: Summers Karin E. , Goff Lindsey K. , Wilson A. Gerry , Gupta Rajnish K. , Lister T. Andrew , Fitzgibbon Jude 
Published: February 2017

PURPOSE: To determine the incidence and frequency of the Bcl-2/IgH rearrangement in the peripheral blood of normal individuals to define the potential complication this may pose for the molecular monitoring of disease in patients with follicular lymphoma (FL). MATERIALS AND METHODS: The incidence and frequency of the major breakpoint cluster region rearrangement in DNA extracted from peripheral blood or lymphoblastoid cell lines from 481 normal individuals was determined using a TaqMan real-time polymerase chain reaction assay (PE Applied Biosystems, Foster City, CA). RESULTS: Twenty three percent of samples were positive for the Bcl-2/IgH rearrangement, with approximately 3% of these at levels of more than 1 in 104 cells. CONCLUSION: The presence of circulating Bcl-2/IgH+ cells, other than those derived from the malignant clone, could confound the detection and quantitation of minimal residual disease in patients with FL, particularly at low levels of tumor burden.
Lack of Prognostic Significance of p53 and K-ras Mutations in Primary Resected Non–Small-Cell Lung Cancer on E4592: A Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy
Authors: Schiller Joan H. , Adak Sudeshna , Feins Richard H. , Keller Steven M. , Fry Willard A. , Livingston Robert B. , Hammond M. Elizabeth M. , Wolf Barbara , Sabatini Linda , Jett James , Kohman Leslie , Johnson David H. 
Published: February 2017

PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.
Phase I Clinical and Pharmacogenetic Trial of Irinotecan and Raltitrexed Administered Every 21 Days to Patients With Cancer
Authors: Stevenson James P. , Redlinger Maryann , Kluijtmans Leo A.J. , Sun Weijing , Algazy Kenneth , Giantonio Bruce , Haller Daniel G. , Hardy Christine , Whitehead Alexander S. , O’Dwyer Peter J. 
Published: February 2017

PURPOSE: Irinotecan and raltitrexed display schedule-dependent synergy in vitro, which supports the clinical investigation of the combination. Functional polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene result in intracellular redistribution of folate derivatives, which may affect raltitrexed-associated cytotoxicity. PATIENTS AND METHODS: Patients with a range of solid cancers and good performance status received irinotecan as a 90-minute infusion on day 1 and raltitrexed as a 15-minute infusion on day 2, repeated every 21 days. Samples were collected for MTHFR C677T genotyping and fasting plasma homocysteine during the first cycle. RESULTS: Thirty-nine assessable patients received 127 cycles of therapy. Irinotecan doses ranged from 100 to 350 mg/m2, and raltitrexed, 1.0 to 4.0 mg/m2. Raltitrexed doses of more than 3.0 mg/m2 were not tolerated and were associated with dose-limiting asthenia, diarrhea, and AST/ALT elevation. Irinotecan/raltitrexed doses of 350/3.0 mg/m2 were well-tolerated; principal toxicities included neutropenia, diarrhea, and fatigue. Two partial responses were observed in patients with pretreated gastroesophageal cancers. Homozygotes with the MTHFR 677 TT polymorphism incurred significantly less raltitrexed-associated toxicity than those with either wild-type or heterozygous genotypes (P = .05). No significant differences were noted in plasma homocysteine values between the genotypic subtypes, and plasma homocysteine levels did not predict the risk of toxicity. CONCLUSION: Irinotecan and raltitrexed doses of 350 and 3.0 mg/m2 are recommended for further study on a day 1, 2 schedule every 21 days. Efficacy results suggest that trials in upper and lower gastrointestinal malignancies are warranted. MTHFR C677T genotypes may be predictive of clinical raltitrexed toxicity.
Epoetin Alfa Therapy Increases Hemoglobin Levels and Improves Quality of Life in Patients With Cancer-Related Anemia Who Are Not Receiving Chemotherapy and Patients With Anemia Who Are Receiving Chemotherapy
Authors: Quirt I. , Robeson C. , Lau C. Y. , Kovacs M. , Burdette-Radoux S. , Dolan S. , Tang S. C. , McKenzie M. , Couture F. ,   the Canadian Eprex Oncology Study Group
Published: February 2017

PURPOSE: To evaluate efficacy, safety, and quality of life (QOL) changes with epoetin alfa therapy for anemia in patients with nonmyeloid malignancies.PATIENTS AND METHODS: Anemic cancer patients were enrolled onto this prospective, open-label study from 34 centers across Canada. The trial had two cohorts: patients who were and were not receiving chemotherapy during the 16-week study. All patients initially received epoetin alfa 150 IU/kg subcutaneously three times per week. The dose was doubled after 4 weeks for patients who did not experience sufficient response.RESULTS: Of the 183 patients enrolled in the nonchemotherapy cohort, statistically significant and clinically relevant improvements in QOL were observed with epoetin alfa therapy using both the FACT-An questionnaire and linear analog scale assessment. Hemoglobin levels increased significantly (P < .001; mean increase 2.5 g/dL from baseline to end of study) and these increases were positively correlated with improved QOL and change in Eastern Cooperative Oncology Group (ECOG) scores. There was a significant reduction in the percentage of patients who required blood transfusions. The 218 patients in the chemotherapy cohort also experienced significant improvements in QOL, decreased transfusion use, and increased hemoglobin levels that correlated with QOL improvements and change in ECOG scores. Epoetin alfa was well-tolerated in both cohorts.CONCLUSION: Epoetin alfa administered to patients with cancer-related anemia for up to 16 weeks resulted in significantly improved QOL, increased hemoglobin levels, and decreased transfusion use. These benefits were observed in cancer patients who were not receiving chemotherapy as well as those who were.
Influence of Endocrine-Related Factors on Response to Perioperative Chemotherapy for Patients With Node-Negative Breast Cancer
Authors: Colleoni Marco , Gelber Shari , Coates Alan S. , Castiglione-Gertsch Monica , Gelber Richard D. , Price Karen , Rudenstam Carl-Magnus , Lindtner Jurij , Collins John , Thürlimann Beat , Holmberg Stig B. , Cortes-Funes H. , Simoncini Edda , Murray Elizabeth , Fey Martin , Goldhirsch Aron 
Published: February 2017

PURPOSE: We investigated tumor- and patient-related features that might influence the response to perioperative chemotherapy (PeCT) compared with no adjuvant therapy for patients with node-negative breast cancer. PATIENTS AND METHODS: A total of 1,275 patients were randomized to either no adjuvant treatment (427 patients) or PeCT (848 patients). The following variables thought to have prognostic significance were evaluated: grade, tumor size, estrogen (ER) and progesterone receptor (PgR) content (absent; low, 1 to 9 fmol/mg cytosol protein; or positive, ≥ 10 fmol/mg cytosol protein), c-erbB-2 overexpression, menopausal status, and age. Cox proportional hazards regression models were used to assess the relative influence of these factors to predict the effect of PeCT on disease-free survival (DFS). Median follow-up was 13.5 years. RESULTS: The 10-year DFS percentage for 692 premenopausal patients did not significantly differ between the PeCT and no-adjuvant-treatment groups: 61% and 59%, respectively (relative risk [RR], 0.95; 95% confidence interval [CI], 0.75 to 1.20; P = .70). No predictive factors were identified. For 583 postmenopausal patients, 10-year DFS percentages for the groups were 63% and 58%, respectively (RR, 0.75; 95% CI, 0.58 to 0.93; P = .03). The absence of expression of ER, PgR, or both ER and PgR was the most important factor predicting improved outcome with PeCT among postmenopausal patients. The 10-year DFS percentages were 85% and 53% for the steroid hormone receptor–absent cohort of treated and untreated patients, respectively (RR, 0.18; 95% CI, 0.06 to 0.49; P = .0009). CONCLUSION: The role of PeCT should be explored for patients whose primary tumors do not express steroid hormone receptors, because it is likely that early initiation of treatment is exclusively relevant for such patients.
Multicenter Phase II Trial of Weekly Paclitaxel in Women With Metastatic Breast Cancer
Authors: Perez Edith A. , Vogel Charles L. , Irwin David H. , Kirshner Jeffrey J. , Patel Ravi 
Published: February 2017

PURPOSE: We evaluated the safety and efficacy of weekly paclitaxel therapy in women with metastatic breast cancer in a phase II multicenter trial. Entry criteria were relatively liberal to reflect the heterogeneity of metastatic breast cancer in clinical practice. PATIENTS AND METHODS: Patients had histologically confirmed and measurable metastatic breast cancer. Up to two prior chemotherapy regimens for metastatic disease, including prior therapy with anthracyclines and taxanes and prior high-dose therapy, were allowed. Paclitaxel 80 mg/m2 was administered weekly for 4 weeks per 4-week cycle. RESULTS: We enrolled 212 patients; 211 were assessable for toxicity and 177 were assessable for response. Ninety percent of patients had received prior chemotherapy (adjuvant, metastatic, or both), 46% of patients had three or more involved metastatic sites, and 60% of patients had visceral-dominant disease. Responses were documented on two occasions and were independently reviewed. The overall response rate (complete plus partial response) was 21.5% (95% confidence interval, 15.4% to 27.5%), with 41.8% of patients having disease stabilization. Median time to progression was 4.7 months, and overall survival in all 212 patients enrolled was 12.8 months. Therapy was well tolerated, with a 15% incidence of grade 3/4 hematologic toxicity and a 9% incidence of grade 3 neurotoxicity; other serious toxicities were rare. The response rate and toxicity profile in the 34% of patients ≥ 65 years of age were similar to that of younger patients. CONCLUSION: Weekly paclitaxel therapy was well tolerated and demonstrated reasonable activity in this relatively heavily pretreated population with advanced disease. Further study of weekly paclitaxel in combination therapy is warranted.
Impact of the Media and the Internet on Oncology: Survey of Cancer Patients and Oncologists in Canada
Authors: Chen Xueyu , Siu Lillian L. 
Published: February 2017

PURPOSE: To evaluate the use of the news media and the Internet as sources of medical information by patients and oncologists in Canada and to investigate the impact on patients’ treatment decisions and the patient-doctor relationship. PATIENTS AND METHODS: During a 2-week period, 191 ambulatory patients participated in the survey. Questionnaires were also mailed to Canadian oncologists: 410 of 686 questionnaires were returned (response rate = 60%). RESULTS: Of the 191 patients, 86% wanted as much information as possible about their illness, 54% reported receiving insufficient information, 83% cited physicians as their primary information source, and 7% cited the Internet. Seventy-one percent of patients actively searched for information, and 50% used the Internet. Patients’ opinions about the balance, accuracy, and relevance of news media reports were evenly split. English as the first language, access to the Internet, and use of alternative treatments predicted a higher rate of information seeking. Most oncologists routinely pay some attention to medical news and believe that it is difficult for patients to interpret medical information in the media and on the Internet accurately. Both patients and oncologists agree that information seeking does not affect the patient-physician relationship. CONCLUSION: Information searching is common among cancer patients in Canada. It does not affect the patient-doctor relationship. The media and the Internet are powerful means of medical information dissemination. Strategic efforts are needed to improve the quality of medical news reporting by the media, and to provide guidance for patients to understand their disease and interpret such information better.
ERCC1 and Thymidylate Synthase mRNA Levels Predict Survival for Colorectal Cancer Patients Receiving Combination Oxaliplatin and Fluorouracil Chemotherapy
Authors: Shirota Yoshinori , Stoehlmacher Jan , Brabender Jan , Xiong Yi-Ping , Uetake Hiroyuki , Danenberg Kathleen D. , Groshen Susan , Tsao-Wei Denise D. , Danenberg Peter V. , Lenz Heinz-Josef 
Published: February 2017

PURPOSE: To test the hypotheses of whether the relative mRNA expression of the thymidylate synthase (TS) gene and the excision cross-complementing (ERCC1) gene are associated with response to and survival of fluorouracil (5-FU)/oxaliplatin chemotherapy in metastatic colorectal cancer. PATIENTS AND METHODS: Patients had progressive stage IV disease after unsuccessful 5-FU and irinotecan chemotherapy. All patients were evaluated for eligibility for a compassionate 5-FU/oxaliplatin protocol. cDNA was derived from paraffin-embedded tumor specimens to determine TS and ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based, real-time reverse transcriptase polymerase chain reaction. RESULTS: The median TS gene expression level from 50 metastasized tumors was 3.4 × 10−3 (minimum expression, 0.18 × 10−3;maximum expression, 11.5 × 10−3), and the median ERCC1 gene expression level was 2.53 × 10−3 (minimum, 0.0; maximum, 14.61 × 10−3). The gene expression cutoff values for chemotherapy nonresponse were 7.5 × 10−3 for TS and 4.9 × 10−3 for ERCC1. The median survival time for patients with TS ≤ 7.5 × 10−3 (43 of 50 patients) was 10.2 months, compared with 1.5 months for patients with TS greater than 7.5 × 10−3 (P < .001). Patients with ERCC1 expression ≤ 4.9 × 10−3 (40 of 50 patients) had a median survival time of 10.2 months, compared with 1.9 months for patients with ERCC1 expression greater than 4.9 × 10−3 (P < .001). A TS of 7.5 × 10−3 segregated significantly into response, stable disease, and progression (P = .02), whereas the association between ERCC1 and response did not reach statistical significance (P = .29). CONCLUSION: These data suggest that intratumoral ERCC1 mRNA and TS mRNA expression levels are independent predictive markers of survival for 5-FU and oxaliplatin combination chemotherapy in 5-FU–resistant metastatic colorectal cancer. Precise definition of the best TS cut point will require further analysis in a large, prospective study.
Long-Term Results of Blood and Marrow Transplantation for Hodgkin’s Lymphoma
Authors: Akpek Görgün , Ambinder Richard F. , Piantadosi Steven , Abrams Ross A. , Brodsky Robert A. , Vogelsang Georgia B. , Zahurak Marianna L. , Fuller Donald , Miller Carole B. , Noga Stephen J. , Fuchs Ephraim , Flinn Ian W. , O’Donnell Paul , Seifter Eric J. , Mann Risa B. , Jones Richard J. 
Published: February 2017

PURPOSE: To evaluate the long-term outcome after allogeneic (allo) and autologous (auto) blood or marrow transplantation (BMT) in patients with relapsed or refractory Hodgkin’s lymphoma (HL). PATIENTS AND METHODS: We analyzed the outcome of 157 consecutive patients with relapsed or refractory HL, who underwent BMT between March 1985 and April 1998. Patients ≤ age 55 with HLA-matched siblings were prioritized toward allo BMT. The median age was 28 years (range, 13 to 52 years) for the 53 allo patients and 30.5 years (range, 11 to 62 years) for the 104 auto patients. RESULTS: The median follow-up after BMT for surviving patients was 5.1 years (range, 1 to 13.8 years). For the entire group, the probabilities of event-free survival (EFS) and relapse at 10 years were 26% (95% confidence interval [CI], 18% to 33%) and 58% (95% CI, 48% to 69%), respectively. According to multivariate analysis, disease status before BMT (sensitive relapse if responding to conventional-dose therapy or resistant disease if not) (hazard ratio [HR] = 0.39, P < .0001) and date of BMT (HR = 0.93, P = .004) were independent predictors of EFS, whereas only disease status (HR = 0.35, P < .0001) influenced relapse. There was a trend for probability of relapse in sensitive patients to be less after allo BMT at 34% (range, 8% to 59%) versus 51% (range, 36% to 67%) for the auto patients (HR = 0.51, P = .17). There was a continuing risk of relapse or secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) for 12 years after auto BMT, whereas there were no cases of secondary AML/MDS or relapses beyond 3 years after allo BMT. CONCLUSION: There seems to be a clinical graft-versus-HL effect associated with allo BMT. Allo BMT for HL also seems to have a lower risk of secondary AML/MDS than auto BMT. Thus, allo BMT warrants continued study in HL.