The Debate About Maintenance Is Not Over in Small-Cell Lung Cancer

Abstract

TO THE EDITOR:We read with interest the study of Arnold et al 1 about vandetanib as a maintenance therapy in patients with small-cell lung cancer (SCLC). They reported that maintenance therapy in SCLC with both chemotherapy and other agents did not affect the survival. However, a meta-analysis revealed the improvement of survival in SCLC with maintenance chemotherapy. 2 In this metaanalysis, maintenance chemotherapy improved 1-and 2-year overall survival by 9% (from 30% to 39%) and 4% (from 10% to 14%), respectively. Similarly, 1-and 2-year progression-free survival were also improved. Indeed, only a few randomized clinical trials reported so far (three of 14) have shown an overall survival difference in favor of maintenance chemotherapy. It is interesting that in two trials showing the superiority of maintenance chemotherapy, the induction therapy was cyclophosphamide, adriamycin, and vincristine, and the maintenance regimen was etoposide and cisplatin. 3,4 These two trials perhaps show that the inclusion of a less cross-resistant second-line chemotherapeutic regimen might improve the therapeutic efficacy of the whole strategy.Another issue about the study by Arnold et al 1 is that although this was a randomized trial, the patients receiving vandetanib were less likely to have received chemotherapy (28% v 32%) and radiation (34% v 43%) after progression. Could this have affected overall survival? In our opinion, this should be regarded as a confounding factor that could have diminished the survival in the vandetanib arm.In short, we believe the debate about the role of maintenance approaches in the management of SCLC is not over. Biologic agents and/or novel chemotherapeutic regimens should be tested in randomized trials in the maintenance setting.