Randomised trials for concurrent treatment have focused on radiation therapy questions and a variety of chemotherapy regimens have been used, but there is no data to compare one concurrent chemotherapy regimen to another. Concurrent cisplatin and etoposide has been the backbone of most approaches and has become the standard of care. The best toxicity and survival data for this regimen comes from the study of Turrisi et al who asked a radiation therapy question (single daily versus twice daily radiation therapy). Both arms on this study received concurrent cisplatin and etoposide and the doses administered were feasible with either once daily or twice daily irradiation. Rates of myelosuppression were high but mortality was low supporting the contention that dosing was maximal.
Turissi et al, randomised 417 patients with limited small cell lung cancer to either 4 cycles of cisplatin and etoposide with concurrent radiation therapy either given once daily or twice daily. The patients were followed for a median period of 8 years.r
Evidence supporting the commencement of chemotherapy with cisplatin and etoposide promptly without delaying for radiation therapy was presented at ASCO 2012. 219 patients were randomly assigned to commence concurrent radiation therapy (52.5Gy over 25#) with cycle 1 of cisplatin and etoposide chemotherapy, or to commence concurrent radiation therapy with cycle 3 of chemotherapy. All patients received a maximum of 4 cycles of chemotherapy. The results presented at ASCO showed the same overall survival for the initial vs delayed radiation therapy, but higher rates of febrile neutropenia in those starting radiation therapy with cycle 1 of chemotherapy.r
Efficacy
The median follow-up at the time of publication was almost 8 years, the minimal potential follow-up was approaching 5 years. Of the 417 patients 335 had died: 175 in the once daily radiation group and 160 in the twice daily radiation group. After the median follow-up of almost 8 years the median survival was 19 months for the once daily group and 23 months for the twice daily group.r
Overall survivalr
© N Engl J Med 1999
The results of the study of radiation therapy starting with chemotherapy cycles 1 vs 3 presented at ASCO showed the same overall survival for the initial vs delayed radiation therapy (24.1 vs 26.8 months respectively, p= 0.6) and progression-free survival (12.2 vs 12.1 months, p= 0.94), complete response rates (36 vs 38%p=0.77).r
Toxicity
These tables show the toxic effects of combined chemoradiation observed amongst 409 patients, including 28 ineligible patients. Despite major myelosuppression (in about 90% of patients in both groups) there was only one death from myelotoxicity. There were overall 11 treatment related deaths (6 in the group receiving twice daily radiation therapy and 5 in the group receiving once daily RT). No haemopoeitic growth factors were used.r
Toxic effects according to the frequency of the radiation therapyr
© N Engl J Med 1999
Treatment complications according to the frequency or timing of the radiation therapyr
© N Engl J Med 1999
The results of the study of radiation therapy starting with chemotherapy cycles 1 vs 3 presented at ASCO showed rates of any grade of oesophagitis (45 vs 37%, p=0.23). Febrile neutropenia was more common in patients randomised to receive initial concurrent chemoradiation (21.6% vs 10.2%, p=0.02).r