Impact of Randomized Clinical Trials on Clinical Practice Regarding Treatment of Lung Cancer

Abstract

Few data are available on the impact of clinical randomized trials on clinical practice. Since 2000, several trials regarding the effect of perioperative chemotherapy (CT) on survival of non-small cell lung cancer (NSCLC) have been published or reported. Four adjuvant CT trials1The International Adjuvant Lung Cancer Trial Collaborative Group Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer.N Engl J Med. 2004; 350: 351-360Crossref PubMed Scopus (1954) Google Scholar, 2Douillard JY Rosell R De Lena M et al.Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial.Lancet Oncol. 2006; 7: 719-727Abstract Full Text Full Text PDF PubMed Scopus (1200) Google Scholar, 3Kato H Ichinose Y Ohta M et al.A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung.N Engl J Med. 2004; 350: 1713-1721Crossref PubMed Scopus (705) Google Scholar, 4Winton T Livingston R Johnson D et al.Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer.N Engl J Med. 2005; 352: 2589-2597Crossref PubMed Scopus (1548) Google Scholar were positive, and one5Scagliotti GV Fossati R Torri V et al.Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell lung cancer.J Natl Cancer Inst. 2003; 95: 1453-1461Crossref PubMed Scopus (504) Google Scholar failed to confirm a statistically significant role for adjuvant CT. Further, one trial was presented as positive at the 2004 ASCO meeting and became negative in 2006.6Strauss GM Herndon J Maddais M Johnston D Adjuvant chemotherapy in stage IB non small cell lung cancer (NSCLC): update of Cancer and Leukemia Group B (CALGB) protocol 9633.Proc Am Soc Clin Oncol. 2006; 24: 365sGoogle Scholar For neoadjuvant CT, a large trial7Depierre A Milleron B Moro D et al.Phase III trial of neo-adjuvant chemotherapy (NCT) in resectable stage I (except T1N0), II, IIIA non-small cell lung cancer (NSCLC): the French experience.J Clin Oncol. 2001; 20: 247-253Crossref Scopus (579) Google Scholar showed an increase survival of the preoperative CT arm with a survival difference of 8.6% at 4 years. To assess the impact of those trials on practice in France, two telephone surveys were conducted: the first after the results of the first trials in April 2004 and the second in December 2005 after the results of the other studies. A sample of 153 and 152 physicians, respectively, involved in lung cancer treatment were selected from an independent polling organization. Questionnaires describing clinical scenarios were telephoned to those physicians. They were asked their treatment option for two clinical cases of resectable stage IB and IIB NSCLC. Case 1 was a 50-year-old patient with a resectable adenocarcinoma classified T2N0M0 (IB). Case 2 was a 50-year-old patient with resectable small-cell carcinoma classified T2N1M0 (IIB). If perioperative CT was proposed, oncologists were questioned about which CT regimen they would have prescribed to treat this patient. No statistical difference was observed between the two samples of practitioners questioned for the two surveys. In 2004, one third of practitioners would have treated a patient with stage IB disease with perioperative CT before (9%) or after (27%) surgery. In 2005, suggested adjuvant CT increased from 27% to 58% (p < 0.0001), whereas neoadjuvant CT remained stable (p = 0.52). In 2004, most of the practitioners treated stage IIB NSCLC with CT before (47%) or after (44%) surgery. In 2005, adjuvant CT increased from 44% to 76% (p < 0.0001), whereas proportion of neoadjuvant CT remained stable (p < 0.64). The two regimens of CT prescribed were more often cisplatin-vinorelbine for adjuvant CT and cisplatin-gemcitabine for neoadjuvant CT. In a sample of 153 physicians (one third of French oncologists), we found evidence for rapid increase of prescription of adjuvant CT, especially for patients with stage IIB disease. Similarly, in Toronto, Ontario, Canada, the prescription of adjuvant CT nearly doubled (30% vs 56%) after the presentation of positive trials at ASCO 2004.8Visbal A Kassam F Johnson M et al.Review of practice patterns for adjuvant chemotherapy in patients with completely resected non small cell lung cancer.Lung Cancer. 2005; 49: S96-S97Abstract Full Text PDF Google Scholar However, some limitations of our surveys are possible: 1) we reported the attitudes stated by practitioners on the telephone, which may be different from what would be observed in routine practice; and 2) factors other than physician knowledge, including patient's age, co-morbidities, and preference, are involved in a physician's final decision. Additional studies, including medical chart reviews, are still needed to evaluate the impact of evidence-based medicine on clinical practice.