Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan in patients with brain metastases from lung cancer / 肿瘤

ABSTRACT

Objective: To prospectively evaluate the preliminary efficacy and safety of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan in patients with brain metastases from lung cancer. Methods: Between March 2009 and March 2012, 38 lung cancer patients with brain metastases were prospectively recruited in concurrent radiochemotherapy (CRCT) group to receive whole-brain irradiation (40 Gy/20 fractions) plus three-dimensional conformal boost (for patients with no more than 3 lesions and the diameter ≥ 2 cm, a three-dimensional conformal localized boost was given to increase the dosage to 56-60 Gy) combined with concurrent topotecan (1.75 mg/m2, once a week for 4-6 weeks). Another 38 patients with brain metastasis from lung cancer were selected to be recruited in simple radiotherapy (SRT) group to receive simple radiotherapy in the same period. The efficacy and the adverse reactions were evaluated. All the patients were followed-up, and the survival was analyzed. Results: In CRCT group and SRT group, the median progression-free survival (PFS) time of intracranial metastases were 6 and 3 months, respectively; one-year PFS rates were 42.8% and 11.6%, respectively; two-year PFS rates were 21.6% and 8.7%, respectively; the PFS of CRCT group was higher than that of SRT group (χ2 = 6.020, P = 0.014). In CRCT group and SRT group, the median survival (OS) time were 13 and 10 months, respectively; one-year OS rates were 50.8% and 40.4%, respectively; twoyear OS rates were 37.9% and 16.5%, respectively; the OS of CRCT group was not obviously higher than that of SRT group (χ2 = 1.811, P = 0.178). In CRCT group and SRT group, the one-year control rates of intracranial metastases were 75.9% and 41.6%, respectively; two-year control rates of intracranial metastases were 65.2% and 31.2%, respectively; there was a significant difference between the CRCT group and SRT group (χ2 = 3.892, P = 0.049). In CRCT group and SRT group, the one-year control rates of extracranial lesions were 47.8% and 32.5%, respectively; two-year control rates of extracranial lesions were 28.7% and 24.4%, respectively; there was no significant difference between the CRCT group and SRT group (χ2 = 0.610, P = 0.435). The major adverse reactions were myelosuppression and gastrointestinal reactions with no significant difference between the two groups (P > 0.05). Conclusion: Compared with simple radiotherapy, whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan can significantly improve the PFS rate and the control rate of intracranial lesion in patients with brain metastases from lung cancer, and no significant increase in side effects was observed.