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Biomedical subjects

M J Moore

Publications and source records attributed to M J Moore.

At least 73 records · Page 4Linked to original sources
PubMed1998

Use of mesna to prevent ifosfamide-induced urotoxicity.

The purpose of this study was to make evidence-based recommendations regarding the mode, dosage and schedule of delivery of concomitant mesna (sodium-2-mercaptoethanesulfonate) to protect against ifosfamide-induced uroepithelial toxicity. A critical review of the literature from 1966 to 1996 was undertaken on mesna administration via the intravenous, oral, or combined modality routes. Outcome measures of urinary symptoms and macrohematuria were emphasized, since these endpoints of urotoxicity are most clinically relevant. The quality of evidence obtained from published clinical research was evaluated based on guidelines developed by the Canadian Task Force on the Periodic Health Examination. Recommendations are now made according to the strength of available evidence on the proper usage of mesna as a protective agent against ifosfamide-induced urotoxicity. There is good evidence that the use of mesna significantly reduces urinary symptoms of dysuria and frequency, as well as the incidences of macrohematuria and microhematuria, when administered concurrently with any dosage of ifosfamide regardless of tumor site. Mesna, given intravenously or orally, is superior to standard prophylaxis with vigorous hydration and alkalinization of urine. A commonly used schedule of intravenous mesna involves a dose equal to 60% of the total ifosfamide dose, divided into three aliquots and administered at 0 h, 4 h and 8 h after ifosfamide. Combined oral and intravenous mesna delivered in some tested schedules is equivalent to intravenous mesna alone, but the optimal schedule and dosage of combined formulation have not yet been established. There is fair indirect but no direct evidence that oral mesna alone is equivalent to intravenous mesna or combined modality use. Further research issues, such as patient compliance with oral mesna and other routes of mesna delivery, are discussed. Ongoing study in the appropriate use of mesna is needed to maximize its value as a uroprotective agent in the clinical setting.

Antineoplastic Agents, Alkylating↗
PubMed1998

Mood disturbances in motor neurone disease.

This study explores the severity of depression and anxiety experienced by patients suffering from motor neurone disease and seeks to link this to illness progression, recent life events and personality factors. The 18 patients who participated in the study were assessed for the presence of psychiatric symptoms using the Beck Depressive Inventory and the Hospital Anxiety and Depression Scale. The severity of the illness and the life events during the course of the illness were measured using the Norris scale and the Holmes and Rahe Social Readjustment Rating Scale. A personality assessment was made using the Eysenck Personality Questionnaire (EPQ). Only four out of these 18 patients (23%) in the study suffered depression and of these three (17%) were mild and one (6%) was of moderate severity. A further six patients (33%) were rated as borderline depression. Only two patients suffered from an anxiety state and both had concurrent mild depression. No correlations of depression were found with the life events or illness progression. Only the L sub-scale of the EPQ (15.6+/-4.9) exceeds values expected for the general population. Despite the severity and frequency of life events during the course of the illness, most patients do not develop a depressive illness. The reason for this unexpected result is unclear. Depression is believed to result from underactivity of the serotonergic neurotransmitter system. However, in MND this system is relatively unaffected in contrast to dementia and other neurodegenerative disorders. The patients' high L scores suggest that many may cope with their illness by widespread use of denial as a psychological defence.

Adult↗
PubMed1998

A phase II study of temozolomide in advanced untreated pancreatic cancer.

Temozolomide (SCH 52365) is an imidazotetrazine derivative which exhibits broad spectrum activity against murine tumors and is structurally related to dacarbazine (DTIC). Temozolomide cytotoxicity is schedule dependent in vivo with a daily x 5 schedule showing the highest activity. Oral temozolomide is rapidly and completely absorbed with minimal interpatient and intrapatient variability in pharmacokinetics. Clinical studies have demonstrated activity against melanoma and glioma. The present study examined the activity of oral temozolomide against patients with pancreatic cancer. Patients with advanced pancreatic adenocarcinoma previously untreated with chemotherapy received temozolomide 200 mg/m2/day once daily orally for 5 days with cycles repeated every 28 days. There were 16 patients entered on study with 15 evaluable for response and toxicity. There were no responses seen in 15 evaluable patients with 14 manifesting progressive disease within 2 months of starting therapy. Toxicity was primarily hematological with 3 patients experiencing > or = grade 3 neutropenia and thrombocytopenia respectively. Other toxicities were relatively modest. In conclusion, temozolomide in the once daily x 5 schedule is inactive against adenocarcinoma of the pancreas.

Adenocarcinoma↗
PubMed1998

Adjuvant chemotherapy for high-risk urothelial transitional cell carcinoma: the Princess Margaret Hospital experience.

OBJECTIVE: To review the outcome of adjuvant systemic chemotherapy after surgery for patients with locally advanced urothelial transitional cell carcinoma (TCC) of the bladder and upper urinary tract who were at high risk for recurrence or metastatic spread. PATIENTS AND METHODS: Thirty-five patients (27 men and eight women, median age 59 years) received adjuvant chemotherapy and were followed for a median of 31 months from surgery (range 12-109). All patients had undergone surgery (cystectomy, nephrectomy, nephrouretectomy), with removal of all evident tumour from the following primary sites: bladder (29), renal pelvis (three) and ureter (three). Thirty patients had stage pT3 or greater, 22 had node-positive disease and 16 had vascular invasion. The median interval from surgery to chemotherapy was 2 months. Patients received a median of four courses of cisplatin, methotrexate and vinblastine (n = 23) or the same drugs with doxorubicin (n = 12). RESULTS: Toxicity included nine episodes of febrile neutropenia (one fatal) and six episodes of thromboembolism (one fatal). Eighteen patients (51%) remain alive and free of apparent disease with a median follow-up of 31 months. Actuarial overall and relapse-free survival were 64% and 57% at 2 years and 47% and 53% at 5 years, respectively. For the 22 node-positive patients, the median relapse-free survival and overall survival was 22 months and 33 months, respectively. CONCLUSIONS: Patients with urothelial TCC at high risk of relapse after radical surgery can have a reasonable chance of long-term survival with systemic adjuvant chemotherapy. Treatment is associated with toxicity. The benefits of treatment should be addressed in a large randomized controlled trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Phase I-II study of 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and long-term oral etoposide (FLAME) in unresectable or metastatic gastric cancer.

The objective of this phase I-II study was to determine the efficacy and toxicity of combination chemotherapy with 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and oral etoposide (FLAME) in patients with measurable unresectable or metastatic gastric cancer. Starting doses on the phase I study were as follows: methotrexate 50 mg/m2 intravenous bolus day 1; leucovorin 20 mg/m2 intravenous bolus days 2 through 4, starting 24 hours after the methotrexate dose; 5-fluorouracil 325 mg/m2 intravenous bolus 15 minutes after leucovorin days 2 through 4; doxorubicin 25 mg/m2 intravenous bolus day 8; and oral etoposide 50 mg/day for 14 days, starting on day 8. A new cycle started on day 28. A total of 42 patients were treated--10 patients in the phase I study and 32 patients in the phase II study. Dose-limiting toxicity was encountered in the phase I study on the second escalation step, when doxorubicin was escalated to 30 mg/m2 and 5-fluorouracil was escalated to 350 mg/m2. In the phase II study 28 patients (109 courses) were evaluable for toxicity. Neutropenia grade 3 or more was dose limiting and was documented in 12 patients (43%) during 22 treatment courses (20%). Neutropenia was associated with febrile neutropenia requiring hospitalization in four patients during five courses of therapy. Grade 3 stomatitis and grade 3 diarrhea was infrequent, documented in two patients (two courses) and three patients (four courses), respectively. All other toxicity was grade 1 and grade 2. The combined objective response rate in 38 evaluable patients entered in both studies was 23.3% (six partial responses and one complete response). Stable disease was documented in 15 patients (39.5%). The median survival for the 42 patients entered in both trials was 6.9 months (95% confidence interval, 5.9-8.5 months). The objective response rate and median survival for the combined group is comparable with that reported for the etoposide, leucovorin, and 5-fluorouracil (ELF), and 5-fluorouracil and methotrexate (FMTX) regimens in a recently reported, multicenter, phase III study.

Adenocarcinoma↗
PubMed1998

High risk of vascular events in patients with urothelial transitional cell carcinoma treated with cisplatin based chemotherapy.

PURPOSE: We define the incidence of thromboembolic events in patients receiving multiagent chemotherapy for urothelial cancer. MATERIALS AND METHODS: A retrospective chart review of 271 consecutive patients who received multi-agent cisplatin based chemotherapy for transitional cell carcinoma at Princess Margaret Hospital between 1986 and 1996 was performed. Indications for chemotherapy included adjuvant treatment following resection of high risk disease (13%), and primary management of locally advanced and metastatic disease (87%). RESULTS: Vascular events occurred in 35 patients (12.9%) receiving chemotherapy, including 18 deep vein thromboses, 9 pulmonary emboli, 7 arterial thromboses, 3 cerebrovascular events, 1 superficial phlebitis and 1 angina pectoris (4 patients had deep vein thrombosis and pulmonary embolus). Three events were directly fatal. Overall, 3.6% of chemotherapy cycles were complicated by vascular events with 27 events (77%) occurring during the first 2 cycles. Risk factors for vascular events included a large pelvic mass and concomitant peripheral vascular or coronary artery disease. Substantial morbidity was associated with vascular events and median hospital stay of 10 days. CONCLUSIONS: There is a substantial risk of venous and arterial vascular events in patients receiving cisplatin based chemotherapy for urothelial transitional cell carcinoma. Prophylactic anticoagulation should be considered in patients with risk factors for thromboembolic disease.

Adult↗
PubMed1998

Sexual harassment policies in Florida school districts.

Until recently, little attention has focused on the sexual harassment that occurs in primary and secondary schools. Several school-related lawsuits and study results heightened awareness of the issue. This study investigated the extent to which Florida's school districts complied with the Florida Department of Education's (FDOE) recommendation and guidelines for addressing sexual harassment in schools. District equity coordinators were surveyed regarding policy development, implementation, promotion, education, and effects. Policies were collected for analysis. Most districts responded to the strong encouragement of the FDOE and approved a sexual harassment policy incorporating many of the suggested components. However, policies included only basic information when compared with suggestions from the literature. Results suggest problems with sexual harassment will continue due to lack of efforts in promoting awareness of the policy and education about the issue, which scholars insist are necessary for effectiveness.

Adolescent↗
PubMed1998

Phase I and pharmacologic study of 9-aminocamptothecin colloidal dispersion formulation given as a 24-hour continuous infusion weekly times four every 5 weeks.

PURPOSE: 9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin (CMP) derivative that inhibits normal topoisomerase I function. Schedule dependency was noted, with the greatest activity seen in the setting of greater than 24 hours exposure to lactone (L) concentrations > or = 10 nmol/L. In this phase I study, 9-AC was given by a continuous intravenous infusion over 24 hours once weekly times four every 5 weeks. PATIENTS AND METHODS: Twenty patients, of whom 16 had fluorouracil-refractory colorectal cancer (CRC), entered the study. Dose levels were 0.7 mg/m2 (n = 4), 1.4 mg/m2 (n = 3), 1.9 mg/m2 (n = 6), and 1.65 mg/m2 (n = 7). Detailed pharmacokinetic (PK) measurements of 9-AC L and carboxylate (C) were performed on day 1 of cycles 1 and 2. RESULTS: At 1.9 mg/m2, dose-limiting toxicity (DLT) was reached, with three of six patients having grade 4 neutropenia. At 1.65 mg/m2, one of seven patients had grade 4 neutropenia. Nonhematologic toxicity was modest, with diarrhea > or = grade 3 in two patients and lethargy > or = grade 3 in eight. PK/pharmacodynamic (PD) analyses showed marked interpatient variability. Steady-state concentrations (Css) of 9-AC L > or = 10 nmol/L (3.6 microg/L) were seen in five of seven patients at 1.65 mg/m2 and five of six patients at 1.9 mg/m2. Using the sigmoidal maximal effect (Emax) model, 9-AC L area under the concentration-time curve (AUC) and Css correlated with day 15 decrease in neutrophils (R2 = .47), but not platelets. CONCLUSION: The recommended phase II dose of 9-AC colloidal dispersion (CD) given as a 24-hour continuous infusion weekly for 4 of every 5 weeks is 1.65 mg/m2.

Adult↗
PubMed1998

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Canada↗
PubMed1998

The prognostic role of p53, metallothionein, P-glycoprotein, and MIB-1 in muscle-invasive urothelial transitional cell carcinoma.

Tissue from primary tumors was analyzed for 118 patients with urothelial cancer who subsequently received cisplatin-based chemotherapy. Immunohistochemical staining was performed for nuclear p53 reactivity; for two proposed mediators of drug resistance, metallothionein (MT) and P-glycoprotein; and for the cell proliferation marker MIB-1. For each marker, immunoreactivity was expressed as a percentage of positively staining cells, and overall intensity of staining was graded on a scale from 0 to 3. The product of these two measurements was calculated to generate a percentage-intensity index. Clinical data were obtained independently via retrospective chart review. Chemotherapy regimens containing cisplatin (cisplatin, methotrexate, and vinblastine or methotrexate, vinblastine, doxorubicin, and cisplatin) were administered for metastatic disease (n = 64), for locally advanced disease (n = 45), or as an adjuvant treatment (n = 9). The overall response rate was 56% among 99 evaluable patients, and median survival was 12.7 months. By univariate analysis, Eastern Cooperative Oncology Group performance status (P = 0.0025), tumor grade (P = 0.03), percentage of MT staining (P = 0.01), and percentage-intensity index of MT staining (P = 0.04) were significant predictors of response to chemotherapy. The first three of these were significant in a multivariate model (P = 0.05, 0.04, and 0.04, respectively). By subgroup analysis, the percentage of MT staining predicted for response in metastatic disease (P = 0.03), but not in locally advanced disease (P = 0.28). Only performance status was significantly related to overall survival (P = 0.0001, log-rank test) in the whole cohort. Overexpression of MT in the 64 patients with metastatic disease was associated with a shorter survival (P = 0.04). Expression of p53, P-glycoprotein, and MIB-1 did not predict for survival. In conclusion, overexpression of MT is associated with a poorer outcome from chemotherapy, possibly due to cisplatin resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Assessing the impact of chemotherapy on tumor-related symptoms in advanced colorectal cancer.

In all patients with advanced colorectal cancer, disease eventually progresses following fluorouracil (5-FU) therapy, with a worsening of disease-related symptoms and quality of life (QOL). Irinotecan (CPT-11 [Camptosar]) has produced response rates of 16% to 27% in patients with 5-FU-refractory colorectal cancer, along with a modest survival gain and possible palliative benefit. Disease-related symptoms and QOL are major end points of palliation, although few studies have assessed them as primary end points of response. The concept of palliative response benefit has been applied successfully to randomized trials of systemic therapy in prostate and pancreatic cancers. This article will describe how this concept has been used in the design of a current phase II trial assessing the palliative benefit of irinotecan in patients with 5-FU-refractory colorectal cancer. This trial uses disease-related symptoms and performance status as primary end points. Palliative response was defined prospectively as one or more of the following; (1) 50% decrease in pain score; (2) 50% decrease in narcotic analgesic usage; or (3) 10-point increase in Karnofsky performance scale from baseline for 4 weeks, without deterioration of any of these parameters. The difficulties in using patient-oriented end points as response criteria in this trial and in the clinic will be addressed.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Bimolecular exon ligation by the human spliceosome.

Intron excision is an essential step in eukaryotic gene expression, but the molecular mechanisms by which the spliceosome accurately identifies splice sites in nuclear precursors to messenger RNAs (pre-mRNAs) are not well understood. A bimolecular assay for the second step of splicing has now revealed that exon ligation by the human spliceosome does not require covalent attachment of a 3' splice site to the branch site. Furthermore, accurate definition of the 3' splice site in this system is independent of either a covalently attached polypyrimidine tract or specific 3' exon sequences. Rather, in this system 3' splice site selection apparently occurs with a 5' --> 3' directionality.

Adenoviridae↗
PubMed1997

Use of the somatostatin analogue octreotide acetate in the treatment of encephalopathy associated with carcinoid tumor. Case report.

Carcinoid tumors may present in a variety of ways dependent on sites of disease and ectopic hormone secretion. This case report describes a patient having metastatic carcinoid tumor who developed encephalopathy of uncertain etiology. Treatment with the somatostatin analogue octreotide acetate resulted in dramatic improvement in his mental status. Several plausible mechanisms are discussed.

Adult↗
PubMed1997

Gemcitabine: a promising new agent in the treatment of advanced urothelial cancer.

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine (2',2'-difluorodeoxycytidine) in previously untreated patients with advanced transitional cell carcinoma. PATIENTS AND METHODS: Forty-one patients with measurable advanced transitional cell carcinoma who had received no prior chemotherapy for metastatic disease were scheduled to receive gemcitabine 1,200 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 of a 28-day cycle. Prior adjuvant or neoadjuvant therapy for locally advanced disease was allowed if this was completed greater than 1 year prior to study entry. All patients were treated on an outpatient basis. RESULTS: There were three complete responses and six partial responses seen in 37 assessable patients, for an overall response rate of nine of 37 (24.3%; 95% confidence interval, 12 to 41). Four patients remain in remission at 14, 23, 24, and 31 months. The median survival was 8 months with 17% of patients alive at 2 years. Treatment generally was well-tolerated with three patients having > or = grade 3 nonhematologic toxicity, five having grade 3 neutropenia, two having grade 3 thrombocytopenia, and two episodes of febrile neutropenia. Most patients were able to receive the drug as scheduled with the primary reason for dose reduction or dose delay being neutropenia. CONCLUSION: Gemcitabine has promising single-agent activity against urothelial cancer with a favorable toxicity profile. Further studies in combination with other active agents are warranted.

Aged↗
PubMed1997

Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.

PURPOSE: Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer. PATIENTS AND METHODS: One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival. RESULTS: Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated. CONCLUSION: This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

Adult↗
PubMed1997

Other chemotherapy regimens including mitoxantrone and suramin.

This article reviews the role of systemic chemotherapy in the treatment of hormone refractory prostate cancer, with emphasis on the evidence regarding the use of mitoxantrone plus prednisone, suramin, and various investigational regimens. Outcome assessment in this disease has not been uniform; recently evolved measures such as patient-based "palliative" endpoints and prostate-specific antigen responses will be discussed.

Antineoplastic Agents↗
PubMed1997

Technetium-99m-furifosmin as an agent for functional imaging of multidrug resistance in tumors.

UNLABELLED: There has been a preliminary report that furifosmin, like the other lipophilic 99mTc cations sestamibi and tetrofosmin, is a substrate for P-glycoprotein, the membrane transporter that is a mechanism of multidrug resistance (MDR) in tumors. This has been further investigated in the rat mammary carcinoma cell line MatB/WT and its doxorubicin-selected resistant variant MatB/AdrR. METHODS: In vitro studies were performed by adding furifosmin to stirred single-cell suspensions of MatB/WT and MatB/AdrR in the presence or absence of the Pgp-modulating drug PSC833. Dynamic imaging studies over 30 min were performed in rats bearing MatB/WT or MatB/AdrR tumors growing in the leg. RESULTS: Accumulation of furifosmin in MatB/AdrR cells in vitro was much lower than that in MatB/WT cells. The addition of 1 microM PSC833 increased the plateau accumulation in MatB/AdrR cells 2.4-fold, but did not affect accumulation in MatB/WT cells. In rats, furifosmin accumulated rapidly in MatB/WT tumors and washed out with a mean t3 of 78 min. Washout from MAtB/AdrR tumors was more rapid, with a t3 of 46 min (p < 0.025). Following dissection of animals at 30 min, mean tumor-to-muscle ratios were 1.57 and 1.05 in MatB/WT and MatB/ AdrR tumors, respectively (p < 0.025). CONCLUSION: Furifosmin is suitable for functional imaging of multidrug resistance in tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗