bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capecitabine: a novel, orally administered, tumour-activated treatment for colorectal cancer
Authors: Summerhayes Maxwell 
Published: October 2002

Objective. To provide a comprehensive review of the preclinical and clinical pharmacology and toxicology of the fluoropyrimidine, capecitabine, with particular reference to its use in its new indication, advanced colorectal cancer. Data sources. A MEDLINE search was conducted using the term ‘‘capecitabine’’ for the period 1995 -2001. The reference lists from retrieved articles were reviewed and other relevant papers identified. The abstract books from the annual meetings of the American Society of Clinical and Oncology and the European Society of Medical Oncology were also reviewed. Data extraction. The aim of the review was to be comprehensive and descriptive. All studies containing information deemed to be of interest were reviewed by the author, none were excluded on grounds of quality. Data synthesis. Capecitabine is a prodrug of the widely used cytotoxic agent 5-fluorouracil (5-FU). Unlike 5-FU it is extensively and reliably absorbed after oral administration and does not require folinate (FA) potentiation. Activation of capecitabine is a three-step enzymatic process. The final activating enzyme, thymidine phosphorylase, is found in unusually high concentrations in many solid tumours, resulting in preferential delivery of 5-FU to tumour tissues, including that of colorectal cancers, suggesting therapeutic potential in this malignancy. Large, randomized trials have demonstrated that capecitabine fulfils this potential—compared with the widely used ‘‘Mayo’’ regimen of intravenous 5-FU and folinic acid, oral capecitabine (1250 mg/m2 twice daily) produced a superior response rate and a similar time to disease progression and duration of survival. It was also better tolerated than 5-FU/FA—of seven common fluoropyrimidine-induced toxicities, four were significantly less common with capecitabine. Capecitabine also produced significantly less grade 4 toxicity or toxicity requiring hospitalization, though the hand -foot syndrome that characterizes prolonged, continuous exposure to 5-FU was more common after capecitabine.
Adjuvant Tamoxifen Prescription in Women 65 Years and Older With Primary Breast Cancer
Authors: Silliman Rebecca A. , Guadagnoli Edward , Rakowski William , Landrum Mary Beth , Lash Timothy L. , Wolf Robert , Fink Aliza , Ganz Patricia A. , Gurwitz Jerry , Borbas Catherine , Mor Vincent 
Published: October 2002

PURPOSE: We examined patterns of adjuvant tamoxifen discussion and prescription among breast cancer patients age 65 years and older. METHODS: We selected from women diagnosed with primary breast cancer those with (1) stage I (tumor diameter ≥ 1 cm), stage II, or stage IIIa disease; (2) age 65 years or older on the date of diagnosis; and (3) permission from the attending physician to contact. Data were collected from consenting patients’ medical records, telephone interviews with patients, and mailed questionnaires completed by their physicians. RESULTS: We obtained medical record and interview data for 698 patients. The oldest patients (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.23 to 0.87 for those aged 80+ relative to those aged 65 to 69 years old), those with more comorbid conditions (each additional comorbid condition reduced the odds of discussion by 0.84; 95% CI, 0.73 to 0.96), and those who were estrogen receptor–negative (OR, 0.56; 95% CI, 0.32 to 0.99) were less likely to report discussion of tamoxifen therapy with a physician. Older patients (OR, 2.17; 95% CI, 1.18 to 4.01 for 70- to 79-year-olds relative to 65- to 69-year-olds; OR, 2.44; 95% CI, 1.11 to 5.34 for those aged 80+ relative to those aged 65 to 69 years old), those who reported a greater influence of information about tamoxifen on decision-making (an increase in 1 SD increased the odds by 7.43; 95% CI, 4.36 to 12.65), and those whose physicians believed that the benefits of tamoxifen outweighed its risks (an increase in 1 SD increased the odds by 1.87; 95% CI, 1.34 to 2.62) were more likely to be prescribed tamoxifen. CONCLUSION: These findings highlight the key role of communication in the care of older women with breast cancer and its ultimate influence on the receipt of therapy.
Phase I Evaluation of Prolonged-Infusion Gemcitabine With Irinotecan for Relapsed or Refractory Leukemia or Lymphoma
Authors: Bass Adam J. , Gockerman Jon P. , Hammett Eve , DeCastro Carlos M. , Adams David J. , Rosner Gary L. , Payne Nancy , Davis Patti , Foster Traci , Moore Joseph O. , Rizzieri David A. 
Published: October 2002

PURPOSE: To estimate the maximum-tolerated duration of infusion of gemcitabine at 10 mg/m2/min in combination with irinotecan at 40 mg/m2 daily for 3 days in the treatment of relapsed or refractory acute leukemia or lymphoma. PATIENTS AND METHODS: Patients with leukemia or lymphoma were escalated in separate strata. Stratum I consisted of 11 patients, median age of 47 years (range, 18 to 68 years), with relapsed or refractory leukemia. Stratum II contained nine patients, median age of 48 years (range, 39 to 68 years), who had refractory non-Hodgkin’s lymphoma. Patients received irinotecan at 40 mg/m2 daily for 3 days, beginning just before the first dose of gemcitabine. Gemcitabine was given at 10 mg/m2/min, with the total duration adjusted following a modified continuous reassessment model. RESULTS: Severe myelosuppression and stomatitis/esophagitis were the most serious hematologic and nonhematologic toxicities. Several patients developed febrile neutropenia, nausea, or vomiting. In both strata, the maximum recommended duration of infusion of gemcitabine was 12 hours delivered at 10 mg/m2/min (7,200 mg/m2). The overall response rate for one cycle of this therapy in this phase I trial for patients with leukemia was 18% (95% confidence interval, 8% to 45%), and for those with lymphoma, 33% (95% confidence interval, 17% to 66%). CONCLUSION: A prolonged infusion of gemcitabine at 10 mg/m2/min for 12 hours with 3 days of irinotecan at 40 mg/m2/d is a tolerable induction regimen for patients with acute leukemia or lymphoma. Stomatitis/esophagitis should be anticipated; however, this regimen may induce responses in patients with difficult-to-treat hematologic malignancies.
Randomized, Controlled Trial of Written Emotional Expression and Benefit Finding in Breast Cancer Patients
Authors: Stanton Annette L. , Danoff-Burg Sharon , Sworowski Lisa A. , Collins Charlotte A. , Branstetter Ann D. , Rodriguez-Hanley Alicia , Kirk Sarah B. , Austenfeld Jennifer L. 
Published: October 2002

PURPOSE: Expressing emotions and finding benefits regarding stressful experiences have been associated in correlational research with positive adjustment. A randomized trial was performed to compare effects of experimentally induced written emotional disclosure and benefit finding with a control condition on physical and psychological adjustment to breast cancer and to test whether outcomes varied as a function of participants’ cancer-related avoidance. PATIENTS AND METHODS: Early-stage breast cancer patients completing medical treatment were assigned randomly to write over four sessions about (1) their deepest thoughts and feelings regarding breast cancer (EMO group; n = 21), (2) positive thoughts and feelings regarding their experience with breast cancer (POS group; n = 21), or (3) facts of their breast cancer experience (CTL group; n = 18). Psychological (eg, distress) and physical (perceived somatic symptoms and medical appointments for cancer-related morbidities) outcomes were assessed at 1- and 3-month follow-ups. RESULTS: A significant condition × cancer-related avoidance interaction emerged on psychological outcomes; EMO writing was relatively effective for women low in avoidance, and induced POS writing was more useful for women high in avoidance. Significant effects of experimental condition emerged on self-reported somatic symptoms (P = .0183) and medical appointments for cancer-related morbidities (P = .0069). Compared with CTL participants at 3 months, the EMO group reported significantly decreased physical symptoms, and EMO and POS participants had significantly fewer medical appointments for cancer-related morbidities. CONCLUSION: Experimentally induced emotional expression and benefit finding regarding early-stage breast cancer reduced medical visits for cancer-related morbidities. Effects on psychological outcomes varied as a function of cancer-related avoidance.
Multicenter Randomized Phase III Trial Comparing Protracted Venous Infusion (PVI) Fluorouracil (5-FU) With PVI 5-FU Plus Mitomycin in Inoperable Pancreatic Cancer
Authors: Maisey Nick , Chau Ian , Cunningham David , Norman Andrew , Seymour Matt , Hickish Tamas , Iveson Tim , O’Brien Mary , Tebbutt Niall , Harrington Angela , Hill Mark 
Published: October 2002

PURPOSE: To compare protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin (MMC) in patients with advanced pancreatic cancer in a multicenter, prospectively randomized study. PATIENTS AND METHODS: Two hundred eight patients were randomized to PVI 5-FU (300 mg/m2/d for a maximum of 24 weeks) or PVI 5-FU plus MMC (7 mg/m2 every 6 weeks for four courses). The major end points were tumor response, survival, toxicity, and quality of life (QOL). RESULTS: The two treatment groups were balanced for baseline demographic factors, and 62% had metastatic disease. The overall response rate was 8.4% (95% confidence interval [CI]) 3.2% to 13.7% for patients treated with PVI 5-FU alone compared with 17.6%; 95% CI 10.3% to 25.1% for PVI 5-FU plus MMC (P = .04). Median failure-free survival was 2.8 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P = .14). Median survival was 5.1 months for PVI 5-FU and 6.5 months for PVI 5-FU plus MMC (P = .34). Toxicities in both arms were mild. There was an increased incidence of neutropenia in the 5-FU plus MMC arm (P < .01), although no differences in infection were seen. No patients developed hemolytic uremic syndrome. Global QOL improved significantly after 24 weeks of treatment compared with baseline for patients receiving 5-FU plus MMC, although there was no statistically significant difference in QOL between arms. CONCLUSION: PVI 5-FU plus MMC resulted in a superior response rate in comparison with PVI 5-FU alone in advanced pancreatic cancer, but this did not translate into a survival advantage. These results emphasize the importance of chemotherapy in this setting and the continuing value of the fluoropyrimidines in pancreatic cancer.
Prognostic Value of Tumoral Thymidylate Synthase and p53 in Metastatic Colorectal Cancer Patients Receiving Fluorouracil-Based Chemotherapy: Phenotypic and Genotypic Analyses
Authors: Etienne Marie-Christine , Chazal Maurice , Laurent-Puig Pierre , Magné Nicolas , Rosty Christophe , Formento Jean-Louis , Francoual Mireille , Formento Patricia , Renée Nicole , Chamorey Emmanuel , Bourgeon André , Seitz Jean-François , Delpero Jean-Robert , Letoublon Christian , Pezet Denis , Milano Gérard 
Published: October 2002

PURPOSE: The aim of this multicenter prospective study was to evaluate the role of intratumoral parameters related to fluorouracil (FU) sensitivity in 103 metastatic colorectal cancer patients receiving FU–folinic acid. PATIENTS AND METHODS: Liver metastatic biopsy specimens were obtained for all patients and primary tumor biopsy specimens for 54 patients. Thymidylate synthase (TS), folylpolyglutamate synthetase, and dihydropyrimidine dehydrogenase were measured by radioenzymatic assays; TS promoter polymorphism (2R/2R v 2R/3R v 3R/3R) was determined by polymerase chain reaction; and p53 protein and mutations were analyzed by immunoluminometric assay and denaturing gradient gel electrophoresis, respectively. RESULTS: p53 mutations were observed in 56.7% of metastases. TS activity was significantly higher in 2R/3R tumors as compared with 2R/2R or 3R/3R. TS activity in metastasis was the only parameter linked to clinical responsiveness (responders exhibited the lower TS, P = .047). Univariate Cox analyses demonstrated that TS activity in primary tumor (the greater the TS, the poorer the survival; P = .040), TS promoter polymorphism in primary tumor (risk of death of 2R/3R v 2R/2R, 2.68; P = .035), and p53 stop mutation in metastasis (risk of death of stop mutations v wild type, 3.14; P = .018) were the only significant biologic predictors of specific survival. Stepwise analysis did not discriminate between TS activity and TS polymorphism. CONCLUSION: Present results confirm the value of tumoral TS activity for predicting FU responsiveness, point out the importance of detailed p53 mutation analysis for predicting survival, and suggest that TS genotype in primary tumor carries a prognostic value similar to that of TS activity.
Gemcitabine and Docetaxel in Patients With Unresectable Leiomyosarcoma: Results of a Phase II Trial
Authors: Hensley Martee L. , Maki Robert , Venkatraman E. , Geller Gennifer , Lovegren Meghan , Aghajanian Carol , Sabbatini Paul , Tong William , Barakat Richard , Spriggs David R. 
Published: October 2002

PURPOSE: Few chemotherapy agents are active in leiomyosarcoma (LMS), particularly LMS that has progressed after doxorubicin treatment. We sought to determine the response to gemcitabine plus docetaxel among patients with LMS. PATIENTS AND METHODS: Patients with unresectable LMS of uterine (n = 29) or other (n = 5) primary sites who did not respond to zero to two prior chemotherapy regimens were enrolled onto a phase II study of gemcitabine 900 mg/m2 intravenously (IV) on days 1 and 8 plus docetaxel 100 mg/m2 IV on day 8 with granulocyte colony-stimulating factor given subcutaneously on days 9 to 15, delivered every 21 days. Patients with prior pelvic radiation received 25% lower doses of both agents. Gemcitabine was delivered over 30 or 90 minutes in cycles 1 and 2 and by 90-minute infusion in all subsequent cycles. Pharmacokinetic studies assessed in vivo differences in gemcitabine concentrations with different rates of infusion. RESULTS: Thirty-four patients (median age, 55 years; range, 32 to 74 years) have enrolled. Fourteen had received prior pelvic radiation. Sixteen of 34 patients had progressed after doxorubicin-based therapy; 18 had no prior chemotherapy. Among 34 patients, complete response was observed in three patients and partial response in 15, for an overall response rate of 53% (95% confidence interval, 35% to 70%). Seven patients had stable disease. Fifty percent of patients previously treated with doxorubicin responded. Hematologic toxicity was common (neutropenia: grade 3, 15%; grade 4, 6%; thrombocytopenia: grade 3, 26%; grade 4, 3%), but neutropenic fever (6%) and bleeding events (0%) were rare. The median time to progression was 5.6 months (range, 4 to 10 months). CONCLUSION: Gemcitabine plus docetaxel is tolerable and highly active in treated and untreated patients with LMS.
Characterization of two isomeric β-D-glucosiduronic acids derived from 1,2-diethyl-3-hydroxypyridin-4-one (CP94) in rat liver homogenate incubates
Authors: Liu D Y , Liu Z D , Piyamongkol S , Lu S L , Hider R C 
Published: October 2002

Abstract1,2-Diethyl-3-hydroxypyridin-4-one (CP94) is an orally active iron chelator with potential for use in photodynamic therapy. This investigation reports the formation and characterization of two isomeric glucuronides of CP94 in rat liver homogenate incubates. To assign the glucuronidation sites in the CP94 molecule, two O-methylated derivatives of CP94 have been synthesized. By comparing the spectral characteristics of the CP94 3-O- and 4-O-methyl derivatives with CP94 and the CP94 glucuronides formed during incubation, evidence was obtained which enabled the assignment of these two isomeric glucuronides to the 3-O-glucuronide and 4-O-glucuronide of CP94. It was found that the 3-O-glucuronide was the dominant CP94 metabolite under in-vitro conditions. In an attempt to understand the potential influence of structural variation on the glucuronidation of CP94 analogues, the 1-and 2-monoethyl derivatives of CP94 were investigated. The 2-monoethyl derivative of CP94 yielded only the 3-O-glucuronide in rat liver homogenate incubate, while no glucuronide was formed from the 1-monoethyl derivative. In addition, no glucuronide from the 3-O-methyl or 4-O-methyl derivatives of CP94 could be detected. The relevance of these findings to the development of new 3-hydroxypyridin-4-one iron chelators is discussed.
Epidemiological evidence that maternal diabetes does not appear to increase the risk for Down syndrome
Authors: Martínez‐Frías M. L. , Rodríguez‐Pinilla E. , Bermejo E. , Prieto L. 
Published: October 2002

AbstractIn 1997, Narchi and Kulaylat, studying the incidence of Down syndrome in infants of gestational diabetic mothers, concluded that maternal diabetes increases the risk for Down syndrome, but failed to control the maternal age in their analysis. Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we analyzed the relationship between Down syndrome and maternal diabetes mellitus, and maternal gestational diabetes, controlling the maternal age through the pair‐matching analysis, stratifying by maternal age and logistic regression analysis. The analyses show that maternal age is related either to Down syndrome as well as to both types of maternal diabetes. Thus, the overall analysis could be confounded by maternal age. Once we controlled the maternal age, the risk of maternal diabetes mellitus for Down syndrome is: odds ratio (OR) = 0.92 (0.41–2.07); P = 0.83. Controlling maternal age in gestational diabetes, the risk is OR = 1.18 (0.61–2.35); P > 0.70. Based on our results, we conclude that Down syndrome is related to maternal age, but does not seem to be related to any type of maternal diabetes. © 2002 Wiley‐Liss, Inc.
Dextromethorphan for the reduction of immediate and late postoperative pain and morphine consumption in orthopedic oncology patients
Authors: Weinbroum Avi A. , Gorodetzky Alexander , Nirkin Alexander , Kollender Yehuda , Bickels Jacob , Marouani Nissim , Rudick Valery , Meller Isaac 
Published: October 2002

AbstractBACKGROUNDPostoperative pain is mediated centrally by N‐methyl‐D‐aspartate (NMDA) receptors. The beneficial effects of preincision oral dextromethorphan (DM), which is an NMDA antagonist, on postoperative pain and intravenous patient‐controlled analgesia (IV‐PCA) morphine (MO) consumption have been examined in patients undergoing surgery. The authors investigated 75 patients who underwent surgery for bone and soft tissue malignancies, in whom postoperative pain is more severe compared with patients who undergo general surgery.METHODSPatients received placebo, DM 60 mg, or DM 90 mg (25 patients per group) before surgery and on each of the two following days in a randomized, double‐blind, placebo‐controlled manner. Postoperative IV‐PCA MO was started when subjective pain intensity was ≥ 4/10 (visual score) and lasted for 72 hours. Rescue drugs on demand were oral paracetamol or dipyrone.RESULTSThe patients in the DM60 and DM90 groups similarly experienced 50–80% less pain (P < 0.01) compared with patients in the placebo group, both immediately and up to 3 days postoperatively, as well as a 50% reduction in the estimated overall maximal pain intensity (P < 0.01). Both DM groups consumed 50–70% less MO than the nonmedicated individuals in the placebo group (P < 0.01), and their demand for rescue drugs on the first postoperative day also was significantly lower (P < 0.01). Patients in the DM groups also were sedated less (≈ 70%; P < 0.01). There were no differences among the groups in terms of when the patients left their beds, when they were discharged home, or the number of overall side effects.CONCLUSIONSDM is associated with reduced pain intensity, sedation, and analgesic requirements, even in patients undergoing surgery for bone and soft tissue malignancies. A 3‐day DM administration neither increased the incidence of side effects nor accelerated ambulation and discharge home. Cancer 2002;95:1164–70. © 2002 American Cancer Society.DOI 10.1002/cncr.10784
Survey of oncologists' perceptions of barriers to accrual of older patients with breast carcinoma to clinical trials
Authors: Kornblith Alice B. , Kemeny Margaret , Peterson Bercedis L. , Wheeler Judith , Crawford Jeffrey , Bartlett Nancy , Fleming Gini , Graziano Stephen , Muss Hyman , Cohen Harvey Jay ,   Cancer and Leukemia Group B
Published: October 2002

AbstractBACKGROUNDPrior research has documented the under‐representation in clinical trials of older patients with cancer. In part of a larger study to test the magnitude of these barriers to entering eligible older patients with carcinoma of the breast into clinical trials (Cancer and Leukemia Group B [CALGB] trial 9670), barriers to accruing eligible older patients to clinical trials were obtained from the physician's perspective.METHODSOne hundred fifty‐six physicians (85% oncologists) who treated patients with breast carcinoma at 10 CALGB institutions completed a questionnaire concerning what they perceived as barriers to enrolling older patients with breast carcinoma on clinical trials and possible interventions that may improve accrual.RESULTSPhysicians' perceptions of the most important barriers to accrual of older patients were: 1) elderly patients have significant comorbid conditions that are not excluded by the protocol but that may affect how they would respond to treatment (16%); elderly patients have difficulty understanding what is required in a complicated treatment trial, resulting in poor compliance (16%); treatment toxicity (14%); and elderly patients often do not meet the eligibility criteria (15%). Oncologists most frequently suggested that the most effective interventions for improving the accrual of elderly patients to trials included making personnel available in the clinic to explain clinical trials to older patients and their families (25%) and providing physicians with educational materials concerning treatment toxicity in the elderly (18%).CONCLUSIONSPhysicians viewed barriers to accruing older patients with breast carcinoma to clinical trials as multidimensional, with the most important involving protocol requirements, treatment specific issues, and older patients' medical and cognitive characteristics. Thus, a variety of interventions would be needed to improve accrual of older patients to clinical trials, including increasing physicians' knowledge concerning treatment toxicity in the elderly, simplifying protocol requirements, and reducing treatment toxicity. Cancer 2002;95:989–96. © 2002 American Cancer Society.DOI 10.1002/cncr.10792