bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dacarbazine, Cisplatin, and Interferon-Alfa-2b With or Without Interleukin-2 in Metastatic Melanoma: A Randomized Phase III Trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group
Authors: Keilholz Ulrich , Punt Cornelis J.A. , Gore Martin , Kruit Wim , Patel Poulam , Lienard Danielle , Thomas Jose , Proebstle Thomas M. , Schmittel Alexander , Schadendorf Dirk , Velu Thierry , Negrier Sylvie , Kleeberg Ulrich , Lehman Frederic , Suciu Stefan , Eggermont Alexander M.M. 
Published: September 2005

Background Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma. Patients and Methods Patients with advanced metastatic melanoma were randomly assigned to receive dacarbazine 250 mg/m2 and cisplatin 30 mg/m2 on days 1 to 3 combined with interferon-alfa-2b 10 × 106 U/m2 subcutaneously on days 1 through 5 without (arm A) or with (arm B) a high-dose intravenous decrescendo regimen of IL-2 on days 5 through 10 (18 × 106 U/m2/6 hours, 18 × 106 U/m2/12 hours, 18 × 106 U/m2/24 hours, and 4.5 × 106 U/m2 for 3 × 24 hours). Treatment cycles were repeated in the absence of disease progression every 28 days to a maximum of four cycles. Results Three hundred sixty-three patients with advanced metastatic melanoma were accrued. The median survival was 9 months in both arms, with a 2-year survival rate of 12.9% and 17.6% in arms A and B, respectively (P = .32; hazard ratio, 0.90; 95% CI, 0.72 to 1.11). There was also no statistically significant difference regarding progression-free survival (median, 3.0 v 3.9 months) and response rate (22.8% v 20.8%). Conclusion Despite its activity in melanoma as a single agent or in combination with interferon-alfa-2b, the chosen schedule of IL-2 added to the chemoimmunotherapy combination had no clinically relevant activity.
Psychoactive Medications and Risk of Delirium in Hospitalized Cancer Patients
Authors: Gaudreau Jean-David , Gagnon Pierre , Harel François , Roy Marc-André , Tremblay Annie 
Published: September 2005

Purpose Psychoactive medications are biologically plausible and potentially modifiable risk factors of delirium. To date, however, research findings are inconsistent regarding their association with delirium. The association between exposure to anticholinergics, benzodiazepines, corticosteroids, and opioids and the risk of delirium was studied. Patients and Methods A total of 261 hospitalized cancer patients were followed up with repeated assessments by using the Nursing Delirium Screening Scale for up to 4 weeks for incident delirium. Detailed exposure to psychoactive medications was documented daily. Strengths of association with delirium were expressed as hazard ratios (HRs) in univariate and multivariate analyses by using Cox regression models. All medication variables were coded as time-dependent covariates. Whenever possible, exposure was computed by using cumulative daily doses in equivalents; dichotomous cutoffs were determined. Results During follow-up (mean, 8.6 days), 43 patients became delirious (16.5%). Delirium was associated with a history of delirium and the presence of hepatic metastases at admission. Analysis of the effect of medications was performed adjusting for these factors. Patients exposed to daily doses of benzodiazepines above 2 mg (HR, 2.04; 95% CI, 1.05 to 3.97), above 15 mg of corticosteroids (HR, 2.67; 95% CI, 1.18 to 6.03), or above 90 mg of opioids (HR, 2.12; 95% CI, 1.09 to 4.13) had increases in the risks for delirium. We did not observe associations between anticholinergics and risk for delirium. Conclusion Exposure to opioids, corticosteroids, and benzodiazepines is independently associated with an increased risk of delirium in hospitalized cancer patients.
Quantitative Methylation-Specific Polymerase Chain Reaction Gene Patterns in Urine Sediment Distinguish Prostate Cancer Patients From Control Subjects
Authors: Hoque Mohammad Obaidul , Topaloglu Ozlem , Begum Shahnaz , Henrique Rui , Rosenbaum Eli , Van Criekinge Wim , Westra William H. , Sidransky David 
Published: September 2005

Purpose Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA. Patients and Methods We tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14ARF, MGMT, GSTP1, RARβ2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls. Results Promoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARβ2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels. Conclusion Overall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer.
Explaining Differences in Attitude Toward Adjuvant Chemotherapy Between Experienced and Inexperienced Breast Cancer Patients
Authors: Jansen S.J.T. , Otten W. , Baas-Thijssen M.C.M. , van de Velde C.J.H. , Nortier J.W.R. , Stiggelbout A.M. 
Published: September 2005

Purpose Previous studies have shown that patients who have experienced adjuvant chemotherapy (experienced patients) have a more favorable attitude towards chemotherapy than those who have not (inexperienced patients). However, not much is known about the reasons underlying this difference. According to the Theory of Planned Behavior, the attitude towards a particular behavior (eg, accepting chemotherapy) is based on beliefs about the likelihood of outcomes of the behavior and the evaluations of these outcomes. We used this theory to explore in what way the beliefs of experienced patients differed from those of inexperienced patients. Patients and Methods A cross-sectional survey was undertaken among 719 patients who had been treated for early-stage breast cancer between 1998 and 2003. Patients were asked, first, to indicate the likelihood of six positive and six negative outcomes of undergoing chemotherapy and, second, to give their evaluation of these outcomes. Results Four hundred forty-six women filled in the questionnaire (response rate, 62%). As hypothesized, experienced patients (ie, patients who had been treated with adjuvant chemotherapy as part of their primary treatment plan) had a more positive attitude towards chemotherapy. Experienced patients provided higher likelihood estimates of treatment advantages, such as life prolongation. In addition, they evaluated the positive outcomes of chemotherapy more favorably. With regard to the negative outcomes of chemotherapy, few differences were observed between treatment groups. Conclusion Experienced patients have more confidence in the positive outcomes of chemotherapy than inexperienced patients. This might be the result of a cognitive mechanism to justify the way in which patients were treated.
Low-Dose Chemotherapy for Epstein-Barr Virus–Positive Post-Transplantation Lymphoproliferative Disease in Children After Solid Organ Transplantation
Authors: Gross Thomas G. , Bucuvalas John C. , Park Julie R. , Greiner Timothy C. , Hinrich Steven H. , Kaufman Stuart S. , Langnas Alan N. , McDonald Ruth A. , Ryckman Frederick C. , Shaw Byers W. , Sudan Debra L. , Lynch James C. 
Published: September 2005

Purpose To evaluate the efficacy of a low-dose chemotherapy regimen in children with Epstein-Barr virus (EBV) –positive, post-transplantation lymphoproliferative disease (PTLD) after organ transplantation who have experienced failure with front-line therapy for PTLD. Patients and Methods Eligible patients received cyclophosphamide (600 mg/m2 intravenous for 1 day) and prednisone (2 mg/kg orally for 5 days) every 3 weeks for six cycles. Results Thirty-six patients treated on study were assessable for analyses. Front-line therapies for PTLD before study entry included immune suppression reduction or withdrawal (n = 36), antiviral therapy (n = 33), surgical resection (n = 8), rituximab (n = 2), and interferon alfa (n = 1). Reasons for failure of front-line therapy included progressive disease (PD; n = 33) and persistent disease with concurrent allograft rejection (n = 3). Thirty patients (83%) had stage III to IV disease, 92% had extranodal disease, and 75% had ≥ three sites of disease. The overall response rate was 83% (75% complete response + 8% partial response). The relapse rate was 19%, with only one of five relapsed patients alive and disease-free. Four patients presented with fulminant, disseminated PTLD; only one of these four patients achieved a response, and all four died of PD. Two patients died of treatment-related toxicity. Three patients (8%) experienced allograft loss, but two of the three patients are alive and disease-free after a second transplantation. The 2-year overall, relapse-free, and failure-free (without PTLD and with functioning original allograft) survival rates were 73%, 69%, and 67%, respectively. Conclusion This low-dose chemotherapy regimen is effective for children with EBV-positive, nonfulminant PTLD who have experienced treatment failure with front-line therapy, and this study represents the largest series of PTLD patients treated prospectively with a uniform chemotherapy regimen.
Risk-Adapted Androgen Deprivation and Escalated Three-Dimensional Conformal Radiotherapy for Prostate Cancer: Does Radiation Dose Influence Outcome of Patients Treated With Adjuvant Androgen Deprivation? A GICOR Study
Authors: Zapatero Almudena , Valcárcel Francisco , Calvo Felipe A. , Algás Rosa , Béjar Amelia , Maldonado Javier , Villá Salvador 
Published: September 2005

Purpose Multicenter study conducted to determine the impact on biochemical control and survival of risk-adapted androgen deprivation (AD) combined with high-dose three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. Results of biochemical control are reported. Patients and Methods Between October 1999 and October 2001, 416 eligible patients with prostate cancer were assigned to one of three treatment groups according to their risk factors: 181 low-risk patients were treated with 3DCRT alone; 75 intermediate-risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months before and during 3DCRT; and 160 high-risk patients received NAD and adjuvant AD (AAD) 2 years after 3DCRT. Stratification was performed for treatment/risk group and total radiation dose. Results After a median follow-up of 36 months (range, 18 to 63 months), the actuarial biochemical disease-free survival (bDFS) at 5 years for all patients was 74%. The corresponding figures for low-risk, intermediate-risk, and high-risk disease were 80%, 73%, and 79%, respectively (P = .847). Univariate analysis showed that higher radiation dose was the only significant factor associated with bDFS for all patients (P = .0004). When stratified for treatment group, this benefit was evident for low-risk patients (P = .009) and, more interestingly, for high-risk patients treated with AAD. The 5-year bDFS for high-risk patients treated with AAD was 63% for radiation doses less than 72 Gy and 84% for those ≥ 72 Gy (P = .003). Conclusion The results of combined AAD plus high-dose 3DCRT are encouraging. To our knowledge, this is the first study showing an additional benefit of high-dose 3DCRT when combined with long-term AD for unfavorable disease.
Fatigue in Long-Term Hodgkin's Disease Survivors: A Follow-Up Study
Authors: Hjermstad Marianne J. , Fosså Sophie D. , Oldervoll Line , Holte Harald , Jacobsen Anne B. , Loge Jon H. 
Published: September 2005

Purpose To describe total fatigue (TF) and chronic fatigue (CF) in 476 long-term Hodgkin's disease survivors (HDSs). The development in CF over time was explored in 280 of the patients who had also been assessed 8 years earlier. Patients and Methods In 2003, the Fatigue Questionnaire was mailed to 610 successfully treated HDSs at the Norwegian Radium Hospital from 1971 to 1997. Mean TF scores and occurrence of CF were compared with general population (GP) values. Results Four hundred seventy-six complete forms (81%) were received (median age, 46 years; 56% males, median follow-up time, 195 months). There was a positive association between age and TF (P < .05), whereas presence of B symptoms at diagnosis and treatment before 1980 were associated with CF. Mean TF scores were elevated in HDSs compared with the GP (mean TF score, 14.6; 95% CI, 14.1 to 15.7 v 12.1; 95% CI, 11.9 to 12.3, respectively; P < .001), as was the proportion of persons with CF (30% v 11%, respectively; odds ratio = 3.6; P < .001). The 70 patients with CF 8 years earlier still reported higher TF at follow-up than the 210 patients without CF at the previous assessment (mean TF score, 17.0; 95% CI, 15.6 to 18.3 v 13.1; 95% CI, 12.9 to 14.1, respectively; P < .001). Significantly more patients with persisting CF had B symptoms at diagnosis compared with patients who had recovered (P = .05). No significant association with treatment modality and intensity was found. Conclusion Fatigue remains a major complaint in HDSs several years after treatment, but the association between treatment and fatigue still remains unclear. Many HDSs may recover from CF, particularly patients without B symptoms at diagnosis.
Phase I Trial of Tipifarnib in Patients With Recurrent Malignant Glioma Taking Enzyme-Inducing Antiepileptic Drugs: A North American Brain Tumor Consortium Study
Authors: Cloughesy Timothy F. , Kuhn John , Robins H. Ian , Abrey Lauren , Wen Patrick , Fink Karen , Lieberman Frank S. , Mehta Minesh , Chang Susan , Yung Alfred , DeAngelis Lisa , Schiff David , Junck Larry , Groves Morris , Paquette Steve , Wright John , Lamborn Kathleen , Sebti Said M. , Prados Michael 
Published: September 2005

Purpose To determine the maximum-tolerated dose (MTD), toxicities, and clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs (EIAEDs). This study compares the pharmacokinetics and pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs. Patients and Methods Recurrent malignant glioma patients were treated with tipifarnib using an interpatient dose-escalation scheme. Pharmacokinetics and pharmacodynamics were assessed. Results Twenty-three assessable patients taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600 mg bid. There were significant differences in pharmacokinetic parameters at 300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively), the area under the plasma concentration–time curve (AUC)0-12 hours was approximately two-fold lower in patients on EIAEDs. Farnesyltransferase inhibition was noted at all tipifarnib dose levels, as measured in peripheral-blood mononuclear cells (PBMC). Conclusion Toxicities and pharmacokinetics differ significantly when comparing patients on or off EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC0-12 hours, and predose trough concentrations of tipifarnib. Even in the presence of EIAEDs, the levels of tipifarnib were still sufficient to potently inhibit FTase activity in patient PBMCs. The relevance of these important findings to clinical activity will be determined in ongoing studies with larger numbers of patients.
Longitudinal Assessment of Hematopoietic Abnormalities After Autologous Hematopoietic Cell Transplantation for Lymphoma
Authors: Bhatia Ravi , Van Heijzen Khristine , Palmer Ann , Komiya Asako , Slovak Marilyn L. , Chang Karen L. , Fung Henry , Krishnan Amrita , Molina Arturo , Nademanee Auayporn , O'Donnell Margaret , Popplewell Leslie , Rodriguez Roberto , Forman Stephen J. , Bhatia Smita 
Published: September 2005

Purpose Autologous hematopoietic cell transplantation (HCT) is being increasingly used as an effective treatment strategy for patients with relapsed or refractory Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL) but is associated with therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) as a major cause of nonrelapse mortality. The phenomenon of hematopoietic reconstitution after autologous HCT and the role of proliferative stress in the pathogenesis of t-MDS/AML are poorly understood. Patients and Methods Using a prospective longitudinal study design, we evaluated the nature and timing of alterations in hematopoietic progenitors and telomere length after HCT in patients undergoing autologous HCT at City of Hope Cancer Center (Duarte, CA). Results A significant reduction in primitive and committed progenitors was observed before HCT compared with healthy controls. Further profound and persistent reduction in primitive progenitors but only transient reduction in committed progenitors were seen after HCT. Primitive progenitor frequency in pre-HCT marrow and peripheral-blood stem cells predicted for primitive progenitor recovery after HCT. Shortening of telomere length was observed in marrow cells early after HCT, with subsequent restoration to pre-HCT levels. Patients within this cohort who developed t-MDS/AML had reduced recovery of committed progenitors and poorer telomere recovery, possibly indicating a functional defect in primitive hematopoietic cells. Conclusion Our studies suggest that hematopoietic regeneration after HCT is associated with increased proliferation and differentiation of primitive progenitors. Increased proliferative stress on stem cells bearing genotoxic damage could contribute to the pathogenesis of t-MDS/AML. Extended follow-up of a larger number of patients is required to confirm whether alterations in progenitor and telomere recovery predict for increased risk of t-MDS/AML.
Late Effects of Hematopoietic Cell Transplantation Among 10-Year Adult Survivors Compared With Case-Matched Controls
Authors: Syrjala Karen L. , Langer Shelby L. , Abrams Janet R. , Storer Barry E. , Martin Paul J. 
Published: September 2005

PurposeTo determine late effects of hematopoietic cell transplantation (HCT) on health problems and health-related quality of life for 10-year survivors.Patients and MethodsFour hundred five adults consented to the study before HCT. Medical records and standardized self-report measures were maintained prospectively. After 10 years, 137 survivors and nontransplant controls, case-matched on age, sex, and race, completed self-report of medical problems, symptoms, and health-related quality of life.ResultsSurvivors and controls had similar rates of hospitalization and most diseases, but survivors reported an average of 3.5 medical problems versus 1.7 for controls (P < .001). Survivors reported more musculoskeletal stiffness, cramps, weakness and joint swelling (P < .001), cataract surgery (P < .001), hepatitis C (P = .004), sexual problems for men (P = .01) and women (P < .001), restrictions in social function (P = .002), memory and attention concerns (P = .003), urinary frequency or leaking (P = .006), use of psychotropic medication (P = .009), and denial of life and health insurance (P < .001). Survivors and controls did not differ in self-reported rates of osteoporosis, hypothyroidism, employment, marital satisfaction, divorce, or psychological health.ConclusionAlthough indistinguishable in many respects, survivors had more medical needs than controls. Health problems were not focused on specific diseases or limited to survivors with readily identifiable risk factors. Musculoskeletal problems require both screening and research into etiologies and effective treatments. Osteoporosis and hypothyroidism may be underdiagnosed. Survivors require screening for sexual problems, urinary frequency, mood and need for antidepressants or benzodiazepines.
Randomized Phase IIB Trial of BLP25 Liposome Vaccine in Stage IIIB and IV Non–Small-Cell Lung Cancer
Authors: Butts Charles , Murray Nevin , Maksymiuk Andrew , Goss Glenwood , Marshall Ernie , Soulières Denis , Cormier Yvon , Ellis Peter , Price Allan , Sawhney Ravinder , Davis Mary , Mansi Janine , Smith Colum , Vergidis Dimitrios , Ellis Paul , MacNeil Mary , Palmer Martin 
Published: September 2005

Purpose To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non–small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. Patients and Methods Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 μg). Subsequent immunizations were administered at 6-week intervals. Results The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. Conclusion L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.