Perspectives in small cell lung cancer: is something moving?

Small cell lung cancer (SCLC) represents one of the major challenges of the modern oncology. Its very aggressive behavior with rapid growth, early metastasis and rapid development of resistances to treatments, despite an early response, shorten the life expectances of patients affected by the extensive stage disease to approximately 10–12 months from the diagnosis (1) with a 2-year overall survival (OS) rate of 5% (2,3). In effect the first line of treatment, consistent in a doublet of a platinum-based agent and etoposide, obtain an overall response rate (ORR) of approximately 70% (4) that can be partly improved by adding, when possible, prophylactic cranial and thoracic radiation (5,6). However responses to first line have a very limited duration that rarely exceed 6 months (4). At recurrence therapeutic strategies are limited to few options that essentially haven’t changed since 1996 when topotecan was defined as the standard second line. The ORR obtained by topotecan is in the 15% to 24% range, median time to progression (TTP) is 13.3 weeks and median survival time is 25 weeks. These results have been relevant at that time because for the first time single-agent chemotherapy has shown in this setting similar activity to combination chemotherapy with less toxicity (7). However many attempts of improvement in the last 20 years have been conducted with several chemotherapeutic agents, such as irinotecan, gemcitabine or pemetrexed, with unconvincing results (8). Only amrubicin, a fully synthetic 9 amino anthracyclin, pro-drug of amrubicinol, has shown in several phase II and III trial hints of major activity than that of topotecan. In fact in the ACT-1 phase III trial amrubicin has shown an ORR of 31.1% vs. 16.9% in the topotecan control arm (odds ratio 2.223, P<0.0001). However no differences have been seen in term of progression free survival (PFS) and OS, even if in the experimental arm less frequent grade 3–4 hematologic toxicities have been seen (9). On the basis of these data amrubicin has been registered and is available in second line treatment of SCLC in Japan.