ICE-V in small-cell lung cancer

Ifosfamide, carboplatin, and etoposide with midcycle vincristine (ICE-V) regimen, compared with standard chemotherapy, improves overall survival of patients with small-cell lung cancer (SCLC) without compromising the patients’ quality of life, according to the British Medical Research Council Multicenter Randomised LU21 Trial.

The ICE-V drugs, alone and in combination, were known to be highly active against SCLC. On the other hand, the measurement of quality of life (QL) is also essential because of the need to balance the expected impact on QL of treatment toxicity against survival prolongation. The British Medical Research Council Multicenter Randomised LU21 Trial was conducted in patients with SCLC and good performance status to determine whether survival could be improved by administering ICE-V compared with standard practice chemotherapy, and to compare these two regimens in terms of adverse effects of treatment and QL. 402 patients were randomly assigned, 103 of which receive the ICE-V regimen and 199 standard control chemotherapy. Those assigned to the ICE-V regimen were prescribed 6 cycles of chemotherapy at 4-week intervals without dose reduction, while those receiving standard chemotherapy were administered 6 cycles of chemotherapy at 3-week intervals. The recommended regimens were cyclophosphamide, doxorubicin, and etoposide (CDE) and cisplatin and etoposide (CE). The primary outcome measure was overall survival, while the secondary outcome measures were tumour response, adverse effects of treatment, and QL (depression and anxiety, physical symptoms, functional impairment and global QL). In the ICE-V group, of the 203 patients, 153 received 4 or more cycles, 171 (84%) died and 32 were alive at the time of analysis. 160 of the 199 patients in the control group received 4 or more cycles, and 179(89%) died with only 20 alive at the time of analysis. There was a survival advantage to the ICE-V group. The median survival was 15.6 and 11.6 months in the ICE-V and control groups respectively, with an absolute difference of 4 months. The 1-year survival rates were 55% and 45%, and the 2-year survival rates were 20% and 11% (an absolute difference of 95). In terms of adverse effects, sore mouth was more common in the control group, while numbness and septicaemia were more common in the ICE-V group. This, however, did not result in a difference in treatment-reported deaths. Patients also experienced similar levels of QL across the two treatment groups, with statistically significant changes from baseline to 3 months observed for lack of appetite, depression and overall QL in favour of ICE-V. In conclusion, this randomised trial shows that a regimen of ICE-V administered at 4-week intervals significantly improves survival compared with standard, mainly nonplatinum-based chemotherapy in patients with SCLC and good performance status. This occurs with some QL benefits and manageable toxicity, mainly septicaemia, without an increase in treatment-related deaths. The trial therefore supports the use of platinum-based chemotherapy in patients with SCLC and good performance status.