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Use of preoperative chemotherapy with or without postoperative radiotherapy in technically resectable stage IIIA non-small-cell lung cancer |
Goss G, Paszat L, Newman T E, Evans W K, Browman G |
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Authors' objectives To assess the use of preoperative chemotherapy with or without postoperative radiotherapy in technically resectable stage IIIa non-small-cell lung cancer (NSCLC).
Searching MEDLINE was searched from January 1990 to June 1997 for English-language publications using the subject headings: 'carcinoma', 'non-small cell lung', 'lung neoplasms', 'chemotherapy', 'adjuvant', 'clinical trial', 'research design' and 'practice guideline'. The search used the keywords of 'neoadjuvant', 'induction' and 'preoperative'. Recently published articles were also identified by members of the review team. Articles cited in relevant papers and recently published reviews were retrieved. The PDQ database was searched in August 1997 for ongoing trials. The proceedings from the May 1997 meeting of the American Society of Clinical Oncology were also reviewed.
Study selection Study designs of evaluations included in the reviewRandomised controlled trials (RCTs) which administered chemotherapy before surgery and included surgery in both treatment arms.
Specific interventions included in the reviewPreoperative (neoadjuvant) cisplatin-based chemotherapy with or without postoperative radiotherapy. In 3 trials some patients also received post-operative radiotherapy.
Participants included in the reviewPatients with technically resectable state IIA non-small-cell lung cancer.
Outcomes assessed in the reviewSurvival rates.
How were decisions on the relevance of primary studies made?The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.
Assessment of study quality No formal assessment of quality was undertaken.
Data extraction The authors do not state who, or how many of the reviewers, performed the data extraction. Data were extracted for the categories of: study identification, disease stage, description of treatment groups, number of patients per group, median follow-up time in months, median disease-free survival in months, median survival in months, overall survival rate (%), and p value.
Methods of synthesis How were the studies combined?Pooled odds ratios with 95% confidence intervals were calculated using a random-effects model for two of the RCTs. The remaining two trials are discussed in the review but not pooled, as in one survival data were not reported in a way that allowed extraction suitable for pooling and the other the data were incomplete.
How were differences between studies investigated?The authors acknowledge heterogeneity in the review but their method for assessing heterogeneity is not reported.
Results of the review Four RCTs with 194 participants were included in the review.
The pooled OR of the 2-year survival data (2 trials) favours the use of preoperative chemotherapy with or without radiotherapy (OR = 0.18, 95% CI: 0.06, 0.51) which was statistically significant. One trial reported a median survival of 26 months in the treatment group versus 8 months in the control group (p < 0.001). Another 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.
Toxic effects in 1 trial were mild. In the second trial chemotherapy produced more serious myelotoxic effects: grade III or IV neutropenia developed in 80% of patients after their first course of chemotherapy and neutropenic fever necessitated hospital admission in 15%. Of the patients who received more than one cycle of chemotherapy, 70% required dosage reduction because of grade IV neutropenia. Other toxic effects included nausea and vomiting, diarrhea, hypomagnesemia, and alopecia.
Authors' conclusions There is evidence from 4 small RCTs that for patients with technically resectable stage IIIA NSCLC, the use of preoperative cisplatin-based chemotherapy and postoperative radiotherapy results in superior survival compared with surgery and postoperative radiotherapy. Whether the benefits of chemotherapy can be generalised to patients who do not receive postoperative radiotherapy cannot be determined from the existing trials.
CRD commentary The authors have clearly stated their research question and inclusion and exclusion criteria. The literature search appears thorough but the authors may have missed studies published outside the United States by restricting the searches to one database. The quality of the included studies was not formally assessed and the authors have not reported on how the articles were selected, or how many of the reviewers were involved in the data selection and extraction.
The data extraction is reported in tables and text but statistical pooling may not have been appropriate. There were no tests for heterogeneity but the authors have discussed several methodological and data limitations of the review.
The authors conclusions appear to follow from the results but, as the authors acknowledge, these should be viewed with caution because of the stated methodological limitations of the primary studies included in the review.
Implications of the review for practice and research Practice: The authors recommend that for patients presenting with histological evidence of N2 disease considered by the surgeon to be technically resectable and for which surgery is planned, preoperative chemotherapy with or without postoperative radiotherapy be offered.
Research: The authors do not state any implications for further research but do recommend that the literature should be monitored closely for further studies that would inform their recommendations.
Funding Cancer Care Ontario, Ontario Ministry of Health.
Bibliographic details Goss G, Paszat L, Newman T E, Evans W K, Browman G. Use of preoperative chemotherapy with or without postoperative radiotherapy in technically resectable stage IIIA non-small-cell lung cancer. Cancer Prevention and Control 1998; 2(1): 32-39 Other publications of related interest This paper is based on a Practice Guideline produced by Cancer Care Ontario Practice Guidelines Initiative. The series is published on the Internet and regularly updated. To ensure that you are viewing the most up to date version, go the Cancer Care Ontario website at: http://www.cancercare.on.ca/english/toolbox/qualityguidelines/pebc/
Browman GP, Levine MN, Mohide EA, Hayward RS, Pritchard KI, Gafni A, et al. The practice guidelines development cycle: a conceptual tool for practice guidelines development and implementation. J Clin Oncol 1995;13:502-12.
Indexing Status Subject indexing assigned by NLM MeSH Carcinoma, Non-Small-Cell Lung /pathology /therapy; Combined Modality Therapy; Humans; Lung Neoplasms /pathology /therapy; Neoplasm Staging; Randomized Controlled Trials as Topic AccessionNumber 11998003999 Date bibliographic record published 31/08/2000 Date abstract record published 31/08/2000 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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