RESUMEN
BACKGROUND: Concurrent treatment with BRAF inhibitors and palliative radiation therapy (RT) could be associated with increased toxicity, especially skin toxicity. Current Eastern Cooperative Oncology Group (ECOG) consensus guideline recommend ceasing BRAF inhibitors during RT. There is a lack of data regarding concurrent RT with combined BRAF and MEK inhibitors. This single-arm phase I/II trial was designed to assess the safety and tolerability of palliative RT with concurrent Dabrafenib and Trametinib in patients with BRAF-mutant metastatic melanoma. MATERIALS AND METHODS: Patients received Dabrafenib and Trametinib before and during palliative RT to soft tissue, nodal or bony metastases. The RT dose was escalated stepwise during the study period. Toxicity data including clinical photographs of the irradiated area was collected for up to 12 months following completion of RT. RESULTS: Between June 2016 to October 2019, ten patients were enrolled before the study was stopped early due to low accrual rate. Six patients were treated at level 1 (20 Gy in 5 fractions, any location) and 4 patients at level 2a (30 Gy in 10 fractions with no abdominal viscera exposed). All alive patients completed one year of post-RT follow-up. Of the 82 adverse events (AEs) documented, the majority (90%) were grade 1 and 2. Eight grade 3 events (10%) occurred in five patients, only one was treatment-related (grade 3 fever due to Dabrafenib and Trametinib). No patients experienced grade 3 or 4 RT related toxicities, including skin toxicities. One serious AE was documented in relation to a grade 3 fever due to Dabrafenib and Trametinib requiring hospitalisation. CONCLUSIONS: The lack of grade 3 and 4 RT-related toxicities in our study suggests that Dabrafenib and Trametinib may be continued concurrently during fractionated non-visceral palliative RT to extracranial sites.
RESUMEN
BACKGROUND AND AIM: Thoracic radiotherapy administered concurrently with chemotherapy is the standard of care for patients with inoperable stage III non-small cell lung cancer, but the optimal chemotherapy regimen is not clearly established. The objective of this study was to assess outcomes in a large cohort of patients treated with curative-intent using carboplatin and paclitaxel. METHODS: Consecutive patients undergoing curative-intent radiotherapy to 60-66 Gy in 30-33 daily fractions with concurrent weekly carboplatin (AUC = 2) and paclitaxel (45 mg/m(2) /week) between March 2004 and May 2012 were identified from a prospective database and reviewed individually. A minimum follow-up of 3 months was required unless death occurred sooner. Response to treatment was defined according to established guidelines on re-staging computed tomography scan at 3 months. Toxicities were assessed using a standardised scoring system. RESULTS: One hundred and seven patients were analysed. The median follow-up was 43.5 months. Three months after treatment, a complete or partial response was observed in 72 patients (68%), and nine patients (8%) had already died. The overall locoregional failure rate was 47%, and failure eventually occurred at any site in 75 patients (70%). Median progression-free survival, and median survival were 15 and 22 months, respectively. Grade 3-4 neutropaenia, thrombocytopaenia, nephrotoxicity, oesophagitis and pneumonitis were observed in 15%, 1%, 3%, 11% and 9% of patients during treatment, respectively. There was one episode of fatal radiation pneumonitis. CONCLUSION: Treatment with thoracic radiotherapy and concurrent carboplatin and paclitaxel chemotherapy is feasible. Survival and toxicity outcomes compare favorably to those reported using cisplatin-based regimens.
