Randomized phase II trial of weekly dose-intensive chemotherapy or amrubicin plus cisplatin chemotherapy following induction chemoradiotherapy for limited-disease small cell lung cancer (JCOG1011)

- After induction therapy, 39 and 36 were randomized to CODE and AP arms, respectively.
- One-year progression-free survival was 41.0% in the CODE and 54.3% in the AP arms.
- Grade 3 febrile neutropenia occurred in 16% in the CODE and 42% in the AP arms.
- The one-year progression-free survival did not reach the expected 55%.
- Therefore, neither regimen is suitable for a phase III trial.

ObjectivesThe objective of this study was to select, for a phase III trial, the more promising of weekly-dose intensive chemotherapy or amrubicin + cisplatin chemotherapy as subsequent therapy after induction chemoradiotherapy for previously untreated limited-disease small cell lung cancer (LD-SCLC).Materials andMethodsPatients aged 20-70 years with untreated clinical stage II/III LD-SCLC were eligible. After one cycle of accelerated hyperfractionation thoracic radiotherapy with etoposide plus cisplatin, patients without progression were randomized to either 3 cycles of cisplatin 25 mg/m2 (days 1, 8), doxorubicin 40 mg/m2 (day 1), etoposide 80 mg/m2 (days 1-3), and vincristine 1 mg/m2 (day 8) every 2 weeks (CODE) or amrubicin 40 mg/m2 (days 1-3) and cisplatin 60 mg/m2 (day 1) every 3 weeks (AP). The primary endpoint was the one-year progression-free survival (PFS). The sample size was 72 to select the arm yielding a better one-year PFS (55% vs. 65%) with a probability of 80%.ResultsFrom March 2011 to February 2014, 85 patients were registered. After the induction chemoradiotherapy, 75 patients were randomized to CODE (n = 39) or AP (n = 36). The one-year PFS (95% confidence interval) was 41.0% (25.7-55.8) in the CODE group and 54.3% (36.6-69.0) in the AP group. Grade 4 neutropenia/grade 3 febrile neutropenia occurred in 47%/16% in the CODE group and 78%/42% in the AP group.ConclusionThe one-year PFS was better in the AP group, but it did not reach the expected 55%. Therefore, neither regimen is suitable for a phase III trial.