Moderate dose-escalation of combination chemotherapy with concomitant thoracic radiotherapy in limited-disease small-cell lung cancer: Prolonged intrathoracic tumor control and high central nervous system relapse rate

Background: The role of chemotherapy dose-intensification in small-cell lun g cancer (SCLC) remains unclear. This phase I-II study evaluates feasibilit y and outcome of combination chemotherapy at moderately elevated doses with concomitant thoracic radiotherapy in limited-disease SCLC. Patients and methods: Moderately elevated doses of ifosfamide-epirubicin (c ycles 1 and 3) and of carboplatin-etoposide (cycles 2 and 4) were given wit h G-CSF and peripheral blood stem-cell (PBSC) support. Thoracic radiotherap y (40 Gy) was given once daily during the first five days of each cycle. Results: Overal toxicity was acceptable; most common side-effects were myel osuppression and asthenia. All 35 eligible patients responded (23 CR, 12 PR ). Median time to progression was 15 months; median overall survival was 24 .6 months. Only 6 of 25 relapsing patients (24%) presented with a locoregio nal recurrence while 12 of 25 (48%) relapsed in the central nervous system (CNS). Conclusions: This regimen is a feasible dose-intensification with an accept able toxicity profile. Its efficacy was demonstrated by a 100% response rat e, an excellent local tumor control rate and a median survival of 24.6 mont hs. In the absence of PCI, CNS relapse is a major problem if adequate local control is achieved.