bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III Randomized Trial Comparing Three Platinum-Based Doublets in Advanced Non–Small-Cell Lung Cancer
Authors: Scagliotti G.V. , De Marinis F. , Rinaldi M. , Crinò L. , Gridelli C. , Ricci S. , Matano E. , Boni C. , Marangolo M. , Failla G. , Altavilla G. , Adamo V. , Ceribelli A. , Clerici M. , Di Costanzo F. , Frontini L. , Tonato M. 
Published: October 2002

PURPOSE: To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin (reference regimen) in response rate for patients with advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to receive gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 2 every 21 days (GC arm), or paclitaxel 225 mg/m2 (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL·min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m2/wk for 12 weeks then every other week plus cisplatin 100 mg/m2 day 1 every 28 days (VC arm). RESULTS: Six hundred twelve patients were randomized to treatment (205 GC, 204 PCb, and 203 VC). Overall response rates for the GC (30%) and PCb (32%) arms were not significantly different from that of the VC arm (30%). There were no differences in overall survival, time to disease progression, or time to treatment failure. Median survival for the GC, PCb, and VC groups was 9.8, 9.9, and 9.5 months, respectively. Neutropenia was significantly higher on the VC arm (GC 17% or PCb 35% v VC 43% of cycles, P < .001), as was thrombocytopenia on the GC arm (GC 16% v VC 0.1% of cycles, P < .001). Alopecia and peripheral neurotoxicity were most common on the PCb arm, as was nausea/vomiting on the VC arm (P < .05). CONCLUSION: Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.
Combination Therapy With Thalidomide Plus Dexamethasone for Newly Diagnosed Myeloma
Authors: Rajkumar S. Vincent , Hayman Suzanne , Gertz Morie A. , Dispenzieri Angela , Lacy Martha Q. , Greipp Philip R. , Geyer Susan , Iturria Nancy , Fonseca Rafael , Lust John A. , Kyle Robert A. , Witzig Thomas E. 
Published: October 2002

PURPOSE: Multiple myeloma is a malignancy of plasma cells and is characterized by increased marrow angiogenesis. Thalidomide, an agent with antiangiogenic properties, is effective in relapsed myeloma. We report the results of a study combining thalidomide and dexamethasone as initial therapy for myeloma. PATIENTS AND METHODS: Fifty patients with newly diagnosed myeloma were studied. Thalidomide was given at a dose of 200 mg/d orally. Dexamethasone was given at a dose of 40 mg/d orally on days 1 to 4, 9 to 12, and 17 to 20 (odd cycles) and 40 mg/d on days 1 to 4 (even cycles), repeated monthly. RESULTS: Of all 50 patients, a confirmed response was seen in 32 patients yielding a response rate of 64% (95% confidence interval, 49% to 77%). Thirty-one patients (62%) proceeded to stem-cell collection after four cycles of therapy including 26 who underwent stem-cell transplantation and five who chose stem-cell cryopreservation. Major grade 3 or 4 toxicities were observed in 16 patients (32%), and the most frequent were deep vein thrombosis (six patients), constipation (four patients), rash (three patients), and dyspnea (two patients). Three deaths occurred during active therapy because of a pancreatitis, pulmonary embolism, and infection. CONCLUSION: We conclude that the combination of thalidomide plus dexamethasone is a feasible and active regimen in the treatment of multiple myeloma. It merits further study as an oral alternative to infusional chemotherapy with vincristine, doxorubicin, and dexamethasone and other intravenous regimens currently used as pretransplantation induction therapy for myeloma.
Pain and Quality of Life After Treatment in Patients With Locally Recurrent Rectal Cancer
Authors: Esnaola Nestor F. , Cantor Scott B. , Johnson Margo L. , Mirza Attiqa N. , Miller Alexander R. , Curley Steven A. , Crane Christopher H. , Cleeland Charles S. , Janjan Nora A. , Skibber John M. 
Published: October 2002

PURPOSE: Because survival in patients with locally recurrent rectal cancer (LRRC) is limited, pain control and quality of life (QOL) are important parameters. The purpose of this study was to assess the prevalence of posttreatment pain and QOL of patients with LRRC treated with nonsurgical palliation or resection and identify predictors of poor outcome. PATIENTS AND METHODS: Posttreatment pain severity and QOL were prospectively assessed in 45 patients with LRRC using the Brief Pain Inventory and Functional Assessment of Cancer Therapy–Colorectal questionnaire. RESULTS: Fifteen patients received nonsurgical palliation, and 30 patients underwent resection of their pelvic tumors. There was a significant association between higher posttreatment pain scores and worse QOL (P < .001). Patients treated with nonsurgical palliation reported moderate to severe pain beyond the third month of treatment. Resected patients reported comparable levels of pain during the first 3 postoperative years, particularly after bony resections; long-term survivors (beyond 3 years), however, reported minimal pain and good QOL. Female sex, pelvic/sciatic pain at presentation, total pelvic exenteration, and bony resection were associated with higher rates of moderate to severe posttreatment pain (P = .04, P < .001, P = .04, and P = .02, respectively). Pain at presentation was an independent predictor of posttreatment pain (odds ratio, 7.4 [95% confidence interval, 1.8 to 30.3]; P = .006). CONCLUSION: Patients with LRRC treated with nonsurgical palliation or resection experience significant levels of pain after treatment. Close posttreatment pain monitoring is warranted in patients presenting with pelvic pain, and more aggressive pain management strategies may improve posttreatment QOL.
Immunomagnetic Enrichment and Detection of Micrometastases in Colorectal Cancer: Correlation With Established Clinical Parameters
Authors: Weihrauch Martin R. , Skibowski Edmund , Koslowsky Thomas C. , Voiss Wilfried , Re Daniel , Kuhn-Regnier Ferdinand , Bannwarth Carolin , Siedek Michel , Diehl Volker , Bohlen Heribert 
Published: October 2002

PURPOSE: Micrometastatic disease in bone marrow is of prognostic significance in colorectal cancer patients. However, detection rates of standard immunocytology are relatively low. We used magnetic activated cell sorting (MACS), a highly sensitive method, to increase detection rates and correlated the presence of cytokeratin (CK)-expressing cells with clinical parameters. PATIENTS AND METHODS: Bone marrow was obtained from 51 consecutive patients with newly diagnosed colorectal adenocarcinoma who underwent primary surgery and 18 control subjects. International Union Against Cancer (UICC) stage I disease was diagnosed in 11 patients, stage II disease was diagnosed in 14 patients, stage III disease was diagnosed in 12 patients, and stage IV disease was diagnosed in 14 patients. CK-positive cells were enriched and stained with magnetically labeled CAM 5.2 antibodies directed to CK 7 and 8. RESULTS: CK-positive cells were found in 33 (65%) patients and were absent in 18 (35%). Four of 11 (36%) patients with UICC stage I disease, nine of 14 (64%) with stage II diease, eight of 12 (67%) with stage III disease, and 12 of 14 (86%) with stage IV disease were CK-positive. Epithelial cells were more frequently found in pT3/4 (72%) than in pT1/2 (36%) tumors (P = .026), but there was no difference for lymph node status. CK-positive patients had a higher chance for elevated carcinoembryonic antigen (85% v 15%, P = NS) and CA 19-9 levels (92% v 8%, P = .019). There were no significant differences in CA 72-4, sex, age, tumor grading, or tumor localization regarding the presence of CK-positive cells. All control subjects were CK-negative. CONCLUSION: In searching for micrometastases in colorectal cancer patients, we have achieved high detection rates by using MACS. The presence of these cells correlated significantly with tumor stage, tumor extension, and the tumor marker CA 19-9.
Phase I Safety, Pharmacokinetic, and Pharmacodynamic Trial of ZD1839, a Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Five Selected Solid Tumor Types
Authors: Baselga J. , Rischin D. , Ranson M. , Calvert H. , Raymond E. , Kieback D.G. , Kaye S.B. , Gianni L. , Harris A. , Bjork T. , Averbuch S.D. , Feyereislova A. , Swaisland H. , Rojo F. , Albanell J. 
Published: October 2002

PURPOSE: To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS: This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non–small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited. RESULTS: Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for ≥ 3 months; seven of these patients remained on study drug for ≥ 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway. CONCLUSION: ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.
Dosage Adjustment and Pharmacokinetic Profile of Irinotecan in Cancer Patients With Hepatic Dysfunction
Authors: Raymond Eric , Boige Valérie , Faivre Sandrine , Sanderink Ger-Jan , Rixe Olivier , Vernillet Laurent , Jacques Christian , Gatineau Michel , Ducreux Michel , Armand Jean-Pierre 
Published: October 2002

PURPOSE: To determine the recommended dose (RD) and the pharmacokinetic profile of irinotecan and its metabolites in cancer patients with hyperbilirubinemia. PATIENTS AND METHODS: Patients were assigned to four treatment groups according to their baseline total bilirubin level. Patients in group I (bilirubin within normal range) and group II (bilirubin 1.0 to 1.5 times upper limit of normal [ULN]) received a dose of 350 mg/m2 every 3 weeks. Patients in groups III (bilirubin 1.51 to 3.0 times ULN) and IV (bilirubin > 3.1 times ULN) received starting doses of 175 and 100 mg/m2, respectively. RDs were defined according to the dose-limiting toxicity (DLT) experienced at cycle 1. RESULTS: Thirty-three patients including 21 gastrointestinal cancers were included. Grade 4 febrile neutropenia and diarrhea were common DLTs in patients with hyperbilirubinemia. At a dose of irinotecan 350 mg/m2, DLTs were observed in two of seven and one of five patients in groups I and II, respectively. In group III, escalated doses of irinotecan 175, 200, and 240 mg/m2 were associated with DLTs in one of seven, one of five, and three of six patients, respectively. No DLT was observed in group IV. High bilirubin and alkaline phosphatase levels were associated with an exponential decrease in the clearance of irinotecan. Pharmacokinetic analysis showed that the relative increase in exposure was likely caused by reduced biliary excretion. CONCLUSION: We showed that baseline total bilirubin level could be used to determine the appropriate dose of irinotecan in cancer patients with hepatic dysfunction. Doses of 350 mg/m2 and 200 mg/m2 were considered RDs in patients with bilirubin values ≤ 1.5 times ULN and 1.51 to 3.0 times ULN, respectively.
Quality of Breast Cancer Care: What Do We Know?
Authors: Malin Jennifer L. , Schuster Mark A. , Kahn Katherine A. , Brook Robert H. 
Published: October 2002

PURPOSE: To critically review studies that describe patterns of care for breast cancer patients and to examine the data sources used for case identification and determining patterns of care. METHODS: We searched the MEDLINE database (National Library of Medicine, Bethesda, MD) in August 2001 for studies of breast cancer care published from January 1985 to June 2001. Thirty-eight articles, describing 32 studies, met the inclusion criteria for this review. RESULTS: According to the patterns of care literature, approximately 10% of women do not have an axillary lymph node dissection, 11% to 26% do not have their hormone receptor status reported, 20% do not receive radiation after breast-conserving surgery, and 30% to 70% of women with lymph node–positive breast cancer are not prescribed tamoxifen. Twenty-five (78%) of the studies relied on cancer registries for case identification. Cancer registries (47%) and the medical record (38%) were the most frequent sources of data on process of care. Twenty percent of the articles reported using more than one data source to determine patterns of care. CONCLUSION: Although more patterns of care research has taken place in breast cancer than in any other oncologic condition, we found the available data had many limitations. These limitations highlight the challenges of quality-of-care research. To track changes in the quality of cancer care that may result from our rapidly transforming health care system, we need reliable data on the quality of current practice.
The Case Identification Challenge in Measuring Quality of Cancer Care
Authors: Pearson Marjorie L. , Ganz Patricia A. , McGuigan Kimberly , Malin Jennifer R. , Adams John , Kahn Katherine L. 
Published: October 2002

PURPOSE: The delivery of quality care to all patients with cancer has been named as a national priority within the American health care system. This article addresses the issues critical to case identification in cancer quality measurement and recommends possible strategies for accurately identifying a population of cancer patients. METHODS: We present the measurement issues associated with the basic challenges of case identification strategies for quality measurement. We discuss two basic challenges: (1) accurately identifying all patients with the defining characteristics (eg, a diagnosis of breast cancer), and (2) identifying only patients with these characteristics. RESULTS: Possible options for identifying newly diagnosed patients include using claims or other administrative data, cancer registries, cancer registry rapid case ascertainment, pathology laboratories, and physicians’ offices. In the published literature, the sensitivity of claims varies from 75% to 95%, whereas central registries must have a 90% completeness rate to be certified. Most of these approaches, however, involve limitations to obtaining valid and comparable data across multiple settings. CONCLUSION: Using an existing data collection system staffed by skilled data collectors and managers should result in substantially more accurate and timely data. Registry officials and the government agencies that provide their support should be encouraged to adopt quality-of-care analyses as an important purpose of the registry system and to enhance their capacity to rapidly ascertain cases, collect the appropriate identifying information needed for patient contact, and verify stage at diagnosis. In order to meet the growing demand for timely, accurate information about quality of care, registries are likely to require additional support so they can enhance their capacity to rapidly ascertain cases, collect the appropriate identifying information needed for patient contact, and verify stage at diagnosis.
Low Sensitivity of theki-rasPolymerase Chain Reaction for Diagnosing Pancreatic Cancer From Pancreatic Juice and Bile: A Multicenter Prospective Trial
Authors: Trümper Lorenz , Menges Markus , Daus Heiner , Köhler Daniel , Reinhard Jan-Olaf , Sackmann Michael , Moser Cornelius , Sek Alexandra , Jacobs Georg , Zeitz Martin , Pfreundschuh Michael 
Published: October 2002

PURPOSE: Early detection of pancreatic cancer using molecular markers may improve outcome. Mutations of the ki-ras oncogene are detected in 70% to 90% of pancreatic adenocarcinomas. A prospective, partially blinded, multicenter diagnostic trial was performed to test the sensitivity and specificity of the ki-ras polymerase chain reaction (PCR) analysis of pancreatic juice and bile specimens.PATIENTS AND METHODS: Specimens of pancreatic juice and bile were collected from 532 consecutive patients. Mutations in codon 12 of the ki-ras gene were identified by two independent enrichment PCRs and confirmed by direct sequencing.RESULTS: One hundred seventy-four of 532 patients were excluded from the final analysis (reasons: no amplifiable DNA, no specimen or only duodenal juice sent, lost to follow-up). Sixty-three of 358 patients had ductal pancreatic cancer. In 24 (38.1%) of 63 patients, a mutated ki-ras gene was identified in pancreatic juice and/or bile. Ki-ras mutations were found in four (8%) of 50 cases of chronic pancreatitis, in 10 (18.7%) of 53 cases of other malignancies of the pancreaticobiliary tree, and in 14 (7.3%) of 192 cases of benign diseases or normal findings. Sensitivity and specificity of the ki-ras PCR analysis for the detection of pancreatic cancer was 38.1% and 90.5%, respectively.CONCLUSION: In this prospective trial performed in nonselected patients, mutations of the ki-ras gene were detected in 38.1% of cases with pancreatic cancer. This test in its present form is not appropriate to confirm or screen for pancreatic cancer. More sensitive and/or quantitative PCR tests may improve the molecular diagnosis of pancreatic cancer.
Primary Adult Soft Tissue Sarcoma: Time-Dependent Influence of Prognostic Variables
Authors: Stojadinovic Alexander , Leung Denis H.Y. , Allen Peter , Lewis Jonathan J. , Jaques David P. , Brennan Murray F. 
Published: October 2002

PURPOSE: To define prognostic factors for postrelapse survival and their time-dependent influence for adult soft tissue sarcoma (STS). PATIENTS AND METHODS: We analyzed 2,123 patients with completely resected localized primary STS treated from 1982 to 1999. Variables studied included tumor site, size, depth, grade, and resection margin but not treatment other than resection. Landmark time frames were used to assess the influence of disease-free interval (DFI) on disease-specific survival (DSS). DSS was estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and the Cox proportional hazards regression model. Time-dependent stepwise regression analysis evaluated the time-dependent influence of each variable. RESULTS: Two thirds of recurrences developed within 2 years of initial resection. Tumor size (P < .001), grade (P < .001), and microscopic resection margin (P < .001) independently predicted DSS for all STS. Size and grade independently predicted early (DFI ≤ 3 years) and margin late (DFI > 3 years) DSS. Risk of tumor-related death was the same across all sites 3 years postresection and decreased significantly for extremity/trunk STS when DFI exceeded 3 years (P < .001). Influence of initial high-risk factors for tumor-related mortality in extremity/trunk STS decreased by 40% 3 years postresection, but their influence over DSS for non–extremity/trunk sites remained constant over time. Likelihood of complete resection after recurrence (all sites) increased with DFI (9% and 33% for DFI < 6 and > 36 months, respectively). CONCLUSION: Tumor size, grade, and resection margin predict outcome for completely resected STS, and their influence for DSS is time- and site-dependent. The influence of prognostic factors changes over the natural history of extremity/trunk STS. Time to recurrence exerts significant influence over complete resection rates for recurrent disease.
Expression of CEACAM1 in Adenocarcinoma of the Lung: A Factor of Independent Prognostic Significance
Authors: Laack Eckart , Nikbakht Haleh , Peters Anja , Kugler Christian , Jasiewicz Yvonne , Edler Lutz , Brümmer Jens , Schumacher Udo , Hossfeld Dieter Kurt 
Published: October 2002

PURPOSE: To evaluate the prognostic relevance of CEACAM1 and sialyl Lewis X expression in adenocarcinomas of the lung.PATIENTS AND METHODS: Paraffin wax sections of 93 patients with adenocarcinomas of the lung who underwent surgery between 1990 and 1995 were immunohistochemically investigated using monoclonal anti-CEACAM1 and sialyl Lewis X antibodies. The clinical course of all patients was followed up for a minimum of 5 years.RESULTS: Sixty-one tumors were classified as CEACAM1-positive, and 32 were classified as CEACAM1-negative. Patients with CEACAM1-positive tumors had a significantly poorer overall (P = .00025) and relapse-free (P = .00029) survival than those with CEACAM1-negative tumors. Only three patients did not express the sialyl Lewis X glycotope, whereas 90 tumors (97%) were sialyl Lewis X–positive. In multivariate Cox regression analysis, next to tumor stage and sex, only the expression of CEACAM1 was a significant independent prognostic factor for survival.CONCLUSION: Expression of CEACAM1 was an independent prognostic factor in our patient population and can be used to stratify patients with adenocarcinomas of the lung into low-risk and high-risk groups. In contrast, the expression of sialyl Lewis X was of no prognostic relevance because it was expressed in 97% of all investigated tumors, and most likely has no influence on the function of CEACAM1 in this tumor entity.
Relevance of Bone Marrow Cell Dose on Allogeneic Transplantation Outcomes for Patients With Acute Myeloid Leukemia in First Complete Remission: Results of a European Survey
Authors: Rocha Vanderson , Labopin Myriam , Gluckman Eliane , Powles Ray , Arcese William , Bacigalupo Andrea , Reiffers Josy , Iriondo Arturo , Ringdén Olle , Ruutu Tapani , Frassoni Francesco 
Published: October 2002

PURPOSE: Many attempts have been made to improve the results of allogeneic bone marrow transplantation (alloBMT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1). Bone marrow cell dose has been reported to be an important factor in alloBMT; however, its true impact on relapse incidence (RI), leukemia-free survival (LFS), and nonrelapse mortality (NRM) in a large cohort of patients is unknown.PATIENTS AND METHODS: From January 1992 to December 1999, 572 bone marrow transplantation recipients reported to the European Blood and Marrow Transplantation (EBMT) registry underwent allografting from an HLA-identical sibling donor with an unmanipulated bone marrow for AML in CR1.RESULTS: The median number of nucleated cells (NCs) infused was 2.6 × 108/kg. Estimated 5-year NRM, LFS, and RI for patients receiving more or less than 2.6 × 108NCs/kg were, respectively, 18% ± 5% v 30% ± 5% (P = .001), 68% ± 3% v 46% ± 3% (P < .00001), and 14% ± 4% v 24% ± 5% (P = .004). The association of cell dose with the above outcomes was confirmed in multivariate analyses for NRM (relative risk [RR], 0.53; P = .0007), for LFS (RR, 0.53; P = .00008), and for RI (RR, 0.57; P = .02). The cell dose was also an important factor for neutrophil (RR, 0.76; P = .009) and platelet (RR, 0.77; P = .03) recoveries; however, it did not statistically influence the incidence of acute graft-versus-host disease.CONCLUSION: This study shows that marrow cell dose is one of the most important factors influencing relapse, NRM, and LFS after alloBMT for patients with AML in CR1. Therefore, increasing the marrow cell dose should substantially improve the survival of these patients.