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

Abstract

BackgroundPatients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer.MethodsPatients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT).ResultsFrom March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups.ConclusionCompared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent topotecan chemotherapy significantly improved the PFS rate and the intracranial lesion control rate of patients with brain metastases from lung cancer, and no significant increases in side effects were observed. Based on these results, this treatment method is recommended for phase III clinical trial.

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“…[ 11 12 13 ] However, the results from other studies have not found that systemic therapy has clinical benefits. [ 14 15 16 17 ] Studies involving patients with a limited number of intracranial lesions are limited. The Radiation Therapy Oncology Group (RTOG) 0320 study is a randomized study to explore whether systemic therapy after radiotherapy can improve OS in NSCLC patients with 1–3 BMs.…”

Brain metastasis reirradiation in patients with advanced breast cancer

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Intra‐CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases

“…Topotecan has shown activity in treatment of breast cancer 2,3 . In preclinical and clinical studies, TOPO has demonstrable radiation‐sensitizing effects in multiple solid tumor histologies, including breast carcinoma, 10,11 and in patients with brain metastases 10,12,13 . Although the mechanism is unclear, the radiosensitizing effect may relate to accumulation of cells in S phase and inhibition of DNA repair 10 .…”