Biomedical subjects

W K Evans

Publications and source records attributed to W K Evans.

At least 37 records · Page 2Linked to original sources

PubMed1999

The use of gemcitabine in non-small-cell lung cancer. Provincial Lung Cancer Disease Site Group. Provincial Systemic Treatment Disease Site Group.

GUIDELINE QUESTION: Is there a role for the use of gemcitabine in the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)? OBJECTIVE: To make recommendations about the use of gemcitabine in the management of medically appropriate patients with stage IIIB-IV NSCLC. OUTCOMES: The outcomes of interest were survival, response rate, symptomatic response, response duration and toxicity. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 2 members of the Provincial Lung Cancer Disease Site Group (DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The practice guideline report was reviewed by the Provincial Lung Cancer DSG and by the Systemic Treatment Disease Site Group. These committees comprise medical and radiation oncologists, surgeons, pathologists, nurses, a psychologist, a medical sociologist and administrators. One community representative participated in the development of this practice guideline. QUALITY OF EVIDENCE: Five phase II studies of single-agent gemcitabine in advanced NSCLC were reviewed. Four of these are published as full reports. Two randomized phase II studies comparing single-agent gemcitabine with etoposide plus cisplatin were also reviewed. One of these studies is fully published. Seven phase II studies of gemcitabine in combination with cisplatin and I phase II study of gemcitabine in combination with ifosfamide were reviewed. Three randomized controlled trials (RCTs) and 1 randomized phase II study, published in abstract form, compared gemcitabine combination chemotherapy with cisplatin combination chemotherapy. An additional phase II study, published in abstract form, of gemcitabine as salvage therapy in previously treated patients was also included. BENEFITS: Four phase II studies of single-agent gemcitabine at a dose of 1000 mg/m2 or more showed a combined response rate of 19% (intention-to-treat analysis; 95% confidence interval [CI] 15% to 24%) or 21% (efficacy analysis; 95% CI 17% to 26%) in advanced NSCLC. Median survival ranged from 7 to 9 months. Improvement from baseline in cough, hemoptysis and dyspnea was comparable to what would be expected with radiation therapy and with standard combination chemotherapy regimens. Improvement from baseline in their performance status was reported in 52% of treated patients. The 2 randomized phase II studies reported equivalent response rates for gemcitabine compared with etoposide plus cisplatin; the response data were pooled, which resulted in a nonsignificant benefit for gemcitabine (common odds ratio [OR] 0.90; 95% CI 0.43 to 1.90; p = 0.78). Gemcitabine has most frequently been combined with cisplatin, yielding a combined response rate of 44% (intention-to-treat; 95% CI 36% to 47%) or 45% (efficacy; 95% CI 39% to 51%) from 7 phase II studies. Median survival times ranged from 10 to 14 months. One phase II randomized study compared gemcitabine-cisplatin-vinorelbine vs. cisplatin-epirubicin-vindesine plus lonidamine and demonstrated a higher response rate (62% vs. 35%) in favour of the gemcitabine combination. Three RCTs demonstrated increased response rates for the combination of gemcitabine-cisplatin over either cisplatin alone or other combination regimens [(gemcitabine-cisplatin 35% vs. etoposide-cisplatin 12%; p = 0.001), (gemcitabine-cisplatin 31% vs. cisplatin 9%; p = 0.0001), (gemcitabine-cisplatin 40% vs. mitomycin, ifosfamide, cisplatin 28%; p = 0.03)]. HARMS: The major dose-limiting toxicity is neutropenia. Despite this, infection rates are low. Significant adverse effects that have an impact on the patient's quality of life or require the discontinuance of treatment are reported to be less than with any other single agent or combination of agents. Grade 3 or 4 dyspnea has been reported to occur in fewer than 2% of cases and may be drug related. (ABSTRACT TRUNCATED)

Antimetabolites, Antineoplastic↗

PubMed1998

A phase I study of gemcitabine/cisplatin/etoposide in the treatment of small-cell lung cancer.

PURPOSE: To define the maximum tolerated dose and toxicity of combined cisplatin, etoposide, and gemcitabine in patients with small-cell lung cancer. METHODS: We undertook a phase I study in patients with either extensive small-cell lung cancer with or without prior chemotherapy, or limited disease who had progressed or recurred despite prior treatment. Patients received cisplatin 75 mg/m2 i.v. day 1, etoposide 50-100 mg/m2 i.v. day 1 followed by oral administration of 50-100 mg/m2 days 2 5, and gemcitabine at either 800 or 1000 mg/m2 i.v. days 1 and 8, on a 3 weekly cycle. RESULTS: We treated 20 patients, 14 at the 800 mg/m2 gemcitabine dose level, and six at the 1000 mg/m2 dose level. The protocol initially used an etoposide dose of 100 mg/m2 etoposide daily (i.v. day 1 and orally days 2-5), but the first two patients died of septic complications. With reduction of the etoposide dose to 50 mg/m2 daily x 5, the regimen was well tolerated. At this etoposide dose, neutropenia, mucositis, and gastrointestinal toxicity occurred in one patient at each of the two gemcitabine dose levels. In addition, one patient receiving gemcitabine at the 1000 mg/m2 level experienced a possible allergic reaction. The overall response rate was 54%. Patients on gemcitabine at the 800 mg/m2 level who had not received prior chemotherapy had the highest response rate, at 75%. CONCLUSION: The recommended phase II doses for this regimen are cisplatin 75 mg/m2 i.v. day 1, etoposide 50 mg/m2 i.v. day 1 and orally days 2-5, and gemcitabine 800 mg/m2 i.v. days 1 and 8. Future trials should further examine the optimal relative doses and schedule of gemcitabine and etoposide.

Adult↗

PubMed1998

Cost-effectiveness analysis in oncology.

Physicians are faced with a burgeoning literature of economic studies. However, most physicians have little training in evaluating economic research. Economic studies involve a comparison of the costs and benefits of alternative treatment options. To be of use for medical decision making, they should meet appropriate methodological standards. These include clear specification of the research question and the perspective from which the study is being undertaken, comparison of relevant treatment options, identification and quantification of all important costs and benefits, the use of discounting to allow for time preferences for costs and benefits, and sensitivity analyses to test the robustness of the study's results. Unfortunately, not all adhere to these principles. Physicians need to be able to understand and critically assess the quality of economic studies, and the applicability of the results to their own situation, in order to participate in medical policy decisions.

Cost-Benefit Analysis↗

PubMed1998

Progress of clinical oncology guidelines development using the Practice Guidelines Development Cycle: the role of practitioner feedback.

PURPOSE: To present an update on the development of oncology practice guidelines (PGs) using the Practice Guidelines Development Cycle (Cycle), and to present the results of surveys of oncologists on the first 10 guidelines from the Cancer Care Ontario Practice Guidelines Initiative. METHODS: Practitioners' opinions about guidelines in development were sought using a mail survey method with systematic follow-up. Practitioners were identified by cancer center representatives. Survey packages included evidence-based recommendations (EBRs) and a one-page, nine-item feedback questionnaire. Data were collected between February 1995 and February 1996. RESULTS: Nine hundred fourteen surveys that pertained to 10 guidelines were mailed to 423 practitioners in Ontario. Practitioners included 112 medical oncologists/hematologists, 34 radiation oncologists, 195 surgeons, and 82 practitioners from other medical specialities. One hundred practitioners were located in cancer centers and 323 had community-based practices. The overall response rate by practitioner was 72% and by survey questionnaire, 70%. For the five questionnaire items that assessed guideline quality, approval ratings ranged from 86% to 92%. For the 10 recommendations, 77% ( 63% to 82%) of respondents agreed that the EBR could be approved as a PG. Response and approval rates were consistent across medical specialities and locations of practice. CONCLUSION: The process of obtaining practitioner feedback in the development of PGs is both feasible and useful. The high response rates to the survey indicate that it is possible to obtain broad participation in evidence-based guidelines development throughout Ontario. The changes made to the EBRs in response to feedback suggest that practitioners' opinions can be valuable in shaping evidence-based guidelines.

Evidence-Based Medicine↗

PubMed1998

How interested is the public in genetic testing for colon cancer susceptibility? Report of a cross-sectional population survey.

OBJECTIVE: To assess the public's interest in genetic testing for colon cancer susceptibility, to determine whether provision of information about the accuracy of the test or the population risk of inheriting the colon cancer gene influences interest, to determine the reasons for wanting to be tested and to identify the factors related to interest in testing. DESIGN: A cross-sectional random digit dialing telephone survey of 501 adults. SETTING: Ontario. MAIN OUTCOME MEASURES: Proportion of the public interested in genetic testing; reasons for interest in testing. RESULTS: Of the sample, 39.9% (95% confidence interval [CI] 35.5 to 44.3) stated that they would be very interested in taking a simple blood test if a positive result suggested they had an 80% chance of getting colon cancer sometime during their lifetime. When it was suggested that the test might be accurate only 90% of the time, 33.1% of the sample (95% CI 28.7 to 37.5) still said they would be very interested in testing. When informed that less than 1% of the population inherits the gene for colon cancer, the proportion of the sample stating they would still be very interested in genetic testing fell to 19.2% (95% CI 14.8 to 23.6). The main reasons given for wanting genetic testing were to take preventive action, for peace of mind and curiosity. For respondents who remained interested in testing after being given information about the population risk of inheriting the gene, 2 factors were identified by logistic regression analysis as being independently related to interest: worry about cancer and perceived risk of getting colon cancer. CONCLUSIONS: If the public's interest in testing for colon cancer susceptibility has any influence on its eventual request to be tested, then demand for genetic testing may be considerable once such tests become widely available and known to the public. This study reveals that the public's interest in genetic testing is substantial, although modifiable by the provision of information about the population risk of inheriting a colon cancer gene. This finding suggests that genetic researchers and others should be careful to provide the population risk of inheriting cancer genes when discussing the discovery of these genes with the media. Furthermore, public health educators will need to ensure that information aids include material on familial risk criteria, genetic counselling and genetic testing, as well as on the implications of genetic testing, the general population risk of developing colon cancer and the general population risk of carrying the colon cancer gene. This information should also be provided to those who seek assessment, to health care professionals and to the public.

Adolescent↗

PubMed1998

The consultation to develop a national strategy for cancer staging in Canada.

The lack of uniform recording of stage is a continued barrier to the success of cancer control activities. To review the role of staging, in 1997 the Canadian Committee on Cancer Staging (CCCS) of the National Cancer Institute of Canada (NCIC) formalised a national Consultation initiative with the input of Canadian oncology leaders and international experts on staging. A document was created from prior background work by the Committee and pre-circulated for comment. The document described the importance of cancer staging to patient care, epidemiological and clinical research, and cancer control programs. The document was refined through an iterative process over much of a year which included a formal workshop of the participants and other meetings. The Consultation reaffirmed, with evidence, the central role of staging in all aspects of cancer management. The report of the Consultation, endorsed by the Board of Directors of NCIC, included the following recommendations: 1) the recording of TNM stage by the treating physician should be a standard of care for every cancer patient in Canada where TNM applies, 2) the Canadian Council on Health Services Accreditation should include the TNM stage for every cancer patient as a requirement for hospital accreditation. In conclusion, this process represents an effective method for raising awareness about important medical issues such as staging which are fundamental to the management and control of cancer.

Academies and Institutes↗

PubMed1998

Capturing tumour stage in a cancer information database.

OBJECTIVE: 1. To present the steps taken and lessons learned from one cancer centre's efforts to capture tumour stage information in a cancer database. 2. To determine the accuracy of the stage data through a chart audit. 3. To describe the potential uses of stage information in a cancer centre. DESIGN AND SETTING: This is a retrospective review of an initiative to capture tumour stage information at a regional cancer centre in Ontario. DATA SOURCES: The minutes of the centre's Health Records and Medical Advisory Committees related to staging were reviewed. Data on stage by tumour type was extracted from the centre's Oncology Patient Information System (OPIS). Three hundred and ninety charts were analysed to assess the accuracy of stage information and identify staging errors. Health Information Services workload statistics were reviewed to determine the types and frequency of projects undertaken using stage-related data. RESULTS: In January 1994, the Ottawa Regional Cancer Centre introduced policies and procedures to capture stage-related information. Standardized staging forms and a physician reminder system encouraged the centre's physicians to record tumour stage within 3 months of new patient registration. Of all qualifying cases in 1994, 92% were staged. A medical audit in 1998 of 390 charts from the 3 previous years of staging data revealed that 71.5% of the charts reviewed had been staged completely. Of the incompletely staged cases, 19% to 57% had TNM recorded, but the stage grouping was not recorded, or the "stage" was the extent of disease at the time of disease progression rather than at initial diagnosis (35% to 71%). Physician-related staging errors occurred in 2% to 5% of cases; data-entry errors occurred in 3% to 6% of cases. CONCLUSIONS: Stage information has enabled the centre to better describe its patient clientele for accreditation purposes and to assist researchers in estimating the number of patients potentially available for prospective and retrospective studies. It is being used to guide targeted educational initiatives to selected populations in the region's catchment area and assists administrators in estimating resource needs. Resistance to the capture of stage information can be overcome with persistence, the development of procedures that facilitate physician compliance, including a reminder system, the development of institutional policies and procedures and by feedback on the uses and availability of stage information.

Accreditation↗

PubMed1998

Cost-effectiveness of vinorelbine alone or vinorelbine plus cisplatin for stage IV NSCLC.

Le Chevalier and colleagues have reported results of a randomized controlled clinical trial comparing vinorelbine alone, versus vinorelbine combined with cisplatin, versus standard treatment consisting of vindesine and cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Data on survival in the three study arms and estimates of the resources used to treat these patients were extracted from the publication and inserted into Statistics Canada's POpulation HEalth Model (POHEM). This model includes data on diagnostic methods, treatment, and outcomes appropriate for stage at presentation, health care utilization, and direct care costs ($ Canadian) for best supportive care and for several "standard" chemotherapy regimens used to treat advanced NSCLC. POHEM was then used to model the cost of care per patient and the total burden of cost on the Canadian health care system for each of the chemotherapy treatment strategies and for best supportive care. Based on the published survival curves for each of the vinorelbine regimens, it was possible to estimate the survival gain relative to the standard chemotherapy regimens and to best supportive care, and to estimate their cost-effectiveness as cost per life year gained. Based on this analysis, the most cost-effective standard regimen relative to best supportive care was vinblastine/cisplatin, as it increased average survival while reducing costs by $2,846 per case. Vinorelbine/cisplatin increased survival to a greater degree, but inpatient administration costs associated with the delivery of cisplatin increased treatment costs by $2,983 per case and resulted in a cost-effectiveness ratio of $6,386 per life year gained. As high-dose cisplatin is not routinely administered in the inpatient setting in Canadian institutions, estimates were made of the cost of outpatient administration. The cost of outpatient care was $55 less per case demonstrating that this is the most cost-effective way to administer the regimen. Relative to etoposide/cisplatin and vinblastine/cisplatin, outpatient vinorelbine/cisplatin proved to be cost-effective. Various chemotherapy regimens used in the management of advanced NSCLC all fall within the boundaries of cost-effectiveness generally accepted for health care interventions in Canada. Therefore, cost and cost-effectiveness should not be barriers to the utilization of vinorelbine/cisplatin in Canada.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Use of preoperative chemotherapy with or without postoperative radiotherapy in technically resectable stage IIIA non-small-cell lung cancer. Provincial Lung Cancer Disease Site Group.

GUIDELINE QUESTION: Should preoperative (neoadjuvant) cisplatin-based chemotherapy with or without postoperative radiotherapy be offered to patients with technically resectable stage IIIA non-small-cell lung cancer (NSCLC) to improve survival? (Resectability should be determined preoperatively by a thoracic surgeon.) OBJECTIVE: To make recommendations about the use of preoperative cisplatin-based chemotherapy with or without postoperative radiotherapy in technically resectable stage IIIA NSCLC. OUTCOMES: Survival is the primary outcome of interest. PERSPECTIVES (VALUES): Evidence was collected and reviewed by 4 members of the Lung Cancer Disease Site Group (LCDSG) of the Cancer Care Ontario Practice Guidelines Initiative. The evidence was then presented to the full LCDSG and discussed extensively at 5 of its meetings. The LCDSG comprises medical and radiation oncologists, pathologists, surgeons, epidemiologists, a psychologist and a medical sociologist. A community representative was present at one meeting during which the recommendation was discussed. QUALITY OF EVIDENCE: Four small randomized controlled trials (RCTs) were available for review; 2 were completed and were reported in full in the literature, 1 was published in abstract form, and 1 was closed and was reported as an interim analysis. Although the RCTs used appropriate clinical trials methodology, including planned interim analyses and early stopping rules, retrospective review revealed inconsistencies between the treatment arms for subsets of stage IIIA disease and for prognostic factors. These factors and the small samples in each study limit the interpretation of the results. BENEFITS: The data from 2 of the 4 trials were not combined because the data were not mature in one case and not extractable in the other. The 2 fully published, completed trials reported a survival benefit for patients treated with preoperative chemotherapy with or without postoperative radiotherapy compared with those not given preoperative chemotherapy. One trial reported a median survival of 26 months in the treatment group versus 8 months in the control group (p < 0.001). A second trial reported an estimated median survival of 64 months versus 11 months (p < 0.008) and a 3-year survival rate of 56% versus 15% respectively. A pooled analysis of the 2-year survival data from the 2 completed RCTs yielded an odds ratio for death of 0.18 (95% confidence interval 0.06 to 0.51) in favour of preoperative chemotherapy. HARMS: There was no difference in the postoperative mortality between the trials reviewed. Toxic effects associated with the chemotherapy were limited primarily to neutropenic fever, nausea and vomiting.

Carcinoma, Non-Small-Cell Lung↗

PubMed1998

Follow-up practices for patients with early stage breast cancer: a survey of Canadian oncologists.

The value of routine follow-up programs for patients with early stage breast cancer remains an area of controversy. In recent years, the cost-effectiveness of routine investigations has been questioned, and 2 prospective randomized clinical trials have shown no survival advantage to more intensive diagnostic follow-up approaches. Under the auspices of the Ottawa Regional Cancer Centre, a national survey of the practice patterns of Canadian surgical, radiation and medical oncologists was undertaken to measure current Canadian standards of care and to determine average costs of 5-year follow-up for patients completing primary treatment for stage I and II breast cancer. Standardized questionnaires were sent out to 130 surgeons, 59 radiation oncologists and 89 medical oncologists. The overall response rate was 44%. Based on the frequency of follow-up visits and investigations recommended by respondents, an average cost per patient for a 5-year follow-up plan was derived for each subspecialist group: $791, $911 and $904 for surgeons, radiation oncologists and medical oncologists respectively. Use of a less interventionist follow-up program was estimated to result in a cost saving of $300 per patient over 5 years. The results indicate that, for the most part, Canadian oncologists have been influenced by the available literature concerning follow-up practices and are ordering fewer routine tests. Further cost savings to the Canadian health care system could be achieved with the adoption of even less interventionist follow-up programs.

Breast Neoplasms↗

PubMed1997

Arterial occlusion in patients with peripheral vascular disease treated with platinum-based regimens for lung cancer.

BACKGROUND: Patients with cancer may be hypercoagulable, and smoking can cause both lung cancer and peripheral vascular disease. Cisplatin-based chemotherapy has been reported to cause a variety of vascular side effects. CASE REPORTS: Five patients with bronchogenic carcinoma and peripheral vascular disease developed acute arterial occlusion soon after receiving a combination of cisplatin or carboplatin plus etoposide. All these patients had risk factors for atherosclerosis and three of them had preexisting known peripheral vascular disease. CONCLUSIONS: The occurrence of acute arterial occlusion soon after initiation of chemotherapy suggests that it might have been a complication of this therapy. Hence, caution should be exercised when using platinum-based (and other?) chemotherapy in patients with known moderate or severe peripheral vascular disease.

Aged↗

PubMed1997

Phase II study of a one hour paclitaxel infusion in combination with carboplatin for advanced non-small cell lung cancer.

PURPOSE: To determine the activity, toxicity, and optimal dose of paclitaxel when given by one hour infusion combined with carboplatin in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-seven previously untreated patients with stage IIIB or IV NSCLC were enrolled. Paclitaxel was administered by one hour infusion at a dose of 175 mg/m2 for the first cycle, and was escalated up to 255 mg/m2 over successive cycles if tolerated. In the absence of toxicity, the carboplatin dose was kept constant at an area under the concentration-time curve (AUC) of 6. Cycles were repeated at 3-week intervals until progression or intolerable toxicity occurred. RESULTS: Thirty-six patients were evaluable for toxicity and survival, and thirty-five for responses. The partial response rate was 10 of 35 (29%) and there were no complete responses. The median duration of response was 4.8 months (range 0.5-11.7 months). The median survival duration was 6.5 months, and 1 year survival was 31%. The mean paclitaxel dose was 188 mg/m2. Treatment was generally well tolerated. Four patients (11%) had febrile neutropenia. Five patients (14%) had grade 3 neuropathy, and 4 (11%) had grade 3 nausea and vomiting. Minor toxicities included alopecia, myalgias, arthralgias and stomatitis. CONCLUSIONS: Paclitaxel and carboplatin is a well-tolerated regimen that can safely be given by a one hour paclitaxel infusion. The modest response rate observed in this study may be due to either the low dose-intensity of paclitaxel or the short infusion duration. Further trials to optimize the relative doses of paclitaxel and carboplatin are needed.

Adult↗

PubMed1997

Cyclophosphamide and fluorouracil combined with mitoxantrone versus doxorubicin for breast cancer: superiority of doxorubicin.

PATIENTS AND METHODS: We conducted a randomized, multicenter study of intravenous cyclophosphamide 500 mg/m2 plus fluorouracil 500 mg/m2 combined with either mitoxantrone (Novantrone, Lederle Cyanamid Canada Ltd, Willowdale, Ontario) 10 mg/m2 (CNF) or doxorubicin (Adriamycin, Adria Laboratories of Canada Ltd, Mississauga, Ontario) 50 mg/m2 (CAF) every 3 weeks in advanced breast cancer. RESULTS: The response rate in 249 randomized patients was 36% with CNF (44 of 121) and 48% with CAF (62 of 128) (P = .054), with complete remissions in 10 patients (8.3%) on CNF and in 13 (10.2%) on CAF. If only fully assessable patients are considered, the response rate was 48% (44 of 91) with CNF and 60% (62 of 103) with CAF (P = .098). At time of analysis, all except 10 patients (one CNF and nine CAF) had died. The median survival time with CAF was longer than with CNF (15.2 v 10.9 months; P = .003), and time to progression was also longer with CAF (5.3 v 3.2 months; P < .03). Survival differences remained significant (P = .006) if patients who failed to meet all eligibility criteria were excluded. Favorable prognostic factors for survival in a Cox regression model included good performance status (P < .0001); less than two organ systems involved by tumor (P < .0001); no involvement of lung, liver, or brain (P < .003); involvement of bone or bone marrow (P < .009), prior surgery for breast cancer (P < .006); being premenopausal (P < .03); > or = 3 years from diagnosis until randomization on this study (P < .03); and treatment with CAF (P < .03). Alopecia > or = grade 3 was reported in 55% of patients with CAF and 12% of patients with CNF (P < .001), while other > or = grade 3 toxicities did not differ significantly. Priestman-Baum quality-of-life assessment was comparable on the two study arms. CONCLUSION: In patients with advanced breast cancer, CAF was associated with longer survival than was CNF, with an increase in alopecia, but not in other toxicities.

Adult↗

PubMed1997

Cost of combined modality interventions for stage III non-small-cell lung cancer.

PURPOSE: To evaluate the cost-effectiveness (CE) of new combined modality strategies in patients with stage III non-small-cell lung cancer (NSCLC). METHODS: Recent studies suggest that combined modality therapy confers a survival advantage for patients with stage III NSCLC. Using the Statistics Canada (Ottawa, Canada) lung cancer costing model, we have evaluated the CE of these interventions using 1993 Canadian health care costs and the perspective of the government as payer in a universal health care system. RESULTS: We estimate that the cost to treat a stage IIIa NSCLC patient with preoperative and postoperative chemotherapy would increase by $15,886, and a similar combined modality approach with the addition of postoperative radiotherapy would increase the cost by $22,963. Chemoradiotherapy for stage IIIb NSCLC would produce a smaller incremental cost of approximately $8,912 per case. However, these approaches are remarkably cost-effective, with cost per life-year gained (LYG) ranging from $3,348 to $14,958. Administering all chemotherapy in the outpatient department would improve CE. For sensitivity analysis, we reduced the survival gain that resulted from the three interventions by 25% and 50%, and increased the hospital per diem rates by 10%, 20%, and 30%. CONCLUSION: Even with the most adverse assumptions, the CE estimates were all considered acceptable for new health care technologies in Canada. Overall, it appears that neoadjuvant therapy for stage IIIa NSCLC and combined modality therapy for stage IIIb NSCLC are cost-effective. Economic considerations should not be a barrier to their adoption.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Lung cancer practice guidelines: lessons learned and issues addressed by the Ontario Lung Cancer Disease Site Group.

PURPOSE: The primary objective was to identify the lessons learned and issues addressed by the Disease Site Group (DSG) developing guidelines on lung cancer for practitioners in the province of Ontario. METHODS: The minutes of the Ontario Lung Cancer Disease Site Group (LCDSG) and the meeting notes of a medical sociologist who attended all LCDSG meetings were reviewed to identify the disease-specific and generic issues addressed by the LCDSG during guideline development. RESULTS AND CONCLUSION: The Ontario LCDSG has completed three practice guidelines and has five evidence-based recommendations (EBRs) in production. Topics for guideline development were selected on the basis of known practice variability (eg, advanced-stage non-small-cell lung cancer [NSCLC]); the size of the patient population that could potentially be affected by the guideline; results of phase II trials of new and potentially expensive agents (vinorelbine, paclitaxel, and docetaxel); and randomized controlled clinical trials that support new practice standards (combined modality therapy for unresectable stage III NSCLC). The wording of each EBR reflects the strength and quality of the evidence in support of the treatment option, the primary outcome(s), and the individual physician and discipline values concerning treatment outcomes in the absence of known patient values.

Canada↗

PubMed1997

Cost-effectiveness of gemcitabine in stage IV non-small cell lung cancer: an estimate using the Population Health Model lung cancer module.

Statistics Canada (Ottawa, Ontario, Canada) is in the process of developing the Population Health Model to simulate the health and common illnesses of Canadians. The Population Health Model incorporates a lung cancer module that is based on contemporary Canadian practice. This microsimulation model can be used to estimate the total direct care costs of treating all lung cancer cases diagnosed in Canada and to evaluate the cost and cost-effectiveness of new therapeutic interventions as they are introduced into practice. Gemcitabine, a new nucleoside analogue with a broad spectrum of antitumor activity, is about to be introduced on the Canadian market. The Population Health Model has been used to estimate the cost-effectiveness of gemcitabine in the management of lung cancer over a range of drug doses per treatment cycle starting at 1,000 mg/m2 weekly x 3, as well as potential survival benefits. The survival of stage IV non-small cell lung cancer (NSCLC) patients treated on an international trial of gemcitabine (EO-18) was used to estimate the potential survival gain relative to the survival of stage IV NSCLC patients managed with best supportive care on a randomized trial conducted by the National Cancer Institute of Canada (BR 5). Sensitivity analyses were performed assuming that the survival gain was 25% or 50% less than that reported in the EO-18 trial. The perspective of the economic analysis is that of the government as payer in a universal health care system, and all costs are expressed in 1993 Canadian dollars. Based on the apparent survival advantage of the EO-18 trial in comparison to best supportive care, the cost per life-year gained ranged from $632 to $9,285, depending on the dose per treatment cycle. At the highest dose per cycle (2,000 mg/m2) and with survival reduced by 50% as compared with the EO-18 result, the cost per life-year gained was estimated to be $17,390. From these estimates of direct care costs in the Canadian health care system, gemcitabine appears to be a cost-effective intervention for advanced NSCLC.

Antimetabolites, Antineoplastic↗

PubMed1997

Phase II trial of gemcitabine and weekly cisplatin for advanced non-small cell lung cancer.

Single-agent gemcitabine, when given in doses of > or = 1,250 mg/m2 weekly x 3 with a 1-week break, induces responses in approximately 20% of untreated patients with non-small cell lung cancer. This phase II study was undertaken to determine the efficacy of weekly administration of gemcitabine 1,500 mg/m2 combined with cisplatin 30 mg/m2 x 3 with a rest period of 1 week. Patients younger than 75 years were eligible if they had stage III/IV non-small cell lung cancer, a life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes no more than three times the upper limit of normal, and serum creatinine < or = 130 micromol/L. There were 22 men and 18 women, with a median age of 60 years; 35 had a performance status of 0 or 1. Pathology included adenocarcinoma in 22 patients, squamous cell carcinoma in nine, large cell carcinoma in seven, and mixed non-small cell lung cancer in two. Six patients had stage III and 34 had stage IV tumors. Of the 39 patients eligible for response evaluation, partial remission was seen in 10, for an overall response rate of 26% (95% confidence interval, 12% to 41%). The median duration of response was 19 weeks (range, 7 to 32+ weeks). Grade 3/4 anemia was seen in 11 patients, and 21 patients required red blood cell transfusions. Grade 3/4 neutropenia occurred in 22 patients and grade 3/4 thrombocytopenia in 21 patients. One patient experienced febrile neutropenia Hematologic toxicity, particularly thrombocytopenia, was cumulative over time. Nonhematologic toxicity was modest, but one patient stopped therapy because of a grade 2 skin rash and one stopped because of a grade 4 pulmonary toxicity, both of which were thought to be related to gemcitabine. The modest activity of weekly gemcitabine and weekly cisplatin seen in this trial does not suggest in vivo synergy for these two agents as administered using this schedule and these doses.

Adult↗

PubMed1997

Chemotherapy in stage IV (metastatic) non-small-cell lung cancer. Provincial Lung Disease Site Group.

GUIDELINE QUESTION: In patients with metastatic, stage IV non-small-cell lung cancer (NSCLC) does chemotherapy improve survival and quality of life? OBJECTIVE: To make recommendations about the role of chemotherapy in the treatment of metastatic (stage IV) NSCLC. OUTCOMES: Survival and quality of life are the primary endpoints of interest. Specifically, 1-year survival will be considered. PERSPECTIVE: Evidence was selected and reviewed by 3 medical oncologists and the project coordinator of the Ontario Cancer Treatment Practice Guidelines Initiative. Drafts of this document have been circulated and reviewed by the Provincial Lung Disease Site Group (Lung DSG). The Lung DSG comprises medical and radiation oncologists, pathologists, surgeons, epidemiologists, a psychologists and a medical sociologist. There was no consumer participation in the development of this guideline. QUALITY OF EVIDENCE: There were 3 meta-analyses available for review, but only 1 is discussed in detail. The largest and most comprehensive meta-analysis is based on 11 randomized controlled trials involving 1190 patients. The main comparisons were chemotherapy plus supportive care versus supportive care alone. The largest trial included in the meta-analysis involved randomization of 188 patients, and the smallest trial involved randomization of 32 patients. Only trials that had accrued patients between Jan. 1, 1965, and Dec. 31, 1991, were included in the analysis. BENEFITS: A survival benefit at 1 year was seen for the group of patients treated with chemotherapy (pooled hazard ratio 0.84; 95% confidence interval [CI], 0.74 to 0.95). Subgroup analyses suggested a benefit for patients receiving chemotherapy regimens containing cisplatin (pooled hazard ratio, 0.73; 95% CI, 0.63 to 0.85; relative risk reduction for death, 27%; absolute improvement in 1 year survival, 10%; 95% CI, 5% to 18%; gain in median survival 1.5 months; 95% CI, 1 to 2.5 months). No benefit for patients treated with chemotherapy was found beyond 1 year. None of the randomized trials successfully measured quality of life using QOL assessment instruments. No firm conclusions can be made about the potential benefits (as measured by quality of life) that chemotherapy has for patients with metastatic NSCLC, as there are no available data from randomized controlled trials. However, several trials have documented relief of cancer-related symptoms, such as pain, cough, hemoptysis or dyspnea in the majority (approximately 70%) of patients. HARMS: In a subgroup analysis of trials that used long-term alkylating agents other than cisplatin (an approach no longer used as therapy in NSCLC) as part of the chemotherapy regimen, the meta-analysis demonstrated a detrimental effect of chemotherapy on survival (pooled hazard ratio, 1.26; 95% CI, 0.96 to 1.66, p = 0.09). In general, myelosuppression, sepsis resulting in hospitalization, drug-specific toxicities and death are potential complications of chemotherapy.

Carcinoma, Non-Small-Cell Lung↗