Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicinin 100 patients with small-cell lung cancer: A mature follow-up report

Background: We conducted a phase I-II trial to assess the feasibility and a ctivity of a combination chemotherapy regimen with etoposide, ifosfamide, c isplatin or carboplatin, and epirubicin in limited-disease (LD, stages I-II IB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC). Patients and methods: Standard-dose chemotherapy (SDC) consisting of etopos ide (500 mg/m(2)), ifosfamide (4000 mg/m(2)), cisplatin (50 mg/m(2)) and ep irubicin (50 mg/m(2)) (VIP-E), followed by granulocyte colony-stimulating f actor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qu alifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposi de (1,500 mg/m(2)), ifosfamide (12,000 mg/m(2)), carboplatin (750 mg/m(2)) and epirubicin (150 mg/m(2)) (VIC-E) conditioning. Results of standard-dose VIP-E: Ninety-seven patients were evaluable for re sponse. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; exc luding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The tr eatment-related mortality (TRM) of SDC was 2%. Two additional patients in C R from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCL C and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC. Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-p atients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median sur vivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year su rvival was 50% in LD and 0% in ED SCLC. Conclusions: Despite high response rates, survival after VIP-E SDC and VIC- E HDC in patients with ED SCLC is not superior to that achieved with less t oxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high pr oportion of patients with prior surgical resection) and the high activity o f our chemotherapy regimen in combination with radiotherapy. A study compar ing protocols using simultaneous radiation therapy and chemotherapy, and ot her dose-escalated forms of SDC with HDC is needed to further define the ro le of this treatment modality in SCLC. Given the high rate of secondary mal ignancies observed in patients in CR > 2 years in our study, close follow-u p and early treatment of these neoplasms may contribute to maintaining over all survival in patients with SCLC.