ABSTRACT
BACKGROUND: Effective treatment for patients at least 70 years with newly diagnosed glioblastoma remains challenging and alternatives to conventional cytotoxics are appealing. Autophagy inhibition has shown promising efficacy and safety in small studies of glioblastoma and other cancers. METHODS: We conducted a randomized phase II trial to compare radiotherapy with or without hydroxychloroquine (2:1 allocation). Patients aged at least 70 years with newly diagnosed high-grade glioma deemed suitable for short-course radiotherapy with an ECOG performance status of 0-1 were included. Radiotherapy treatment consisted of 30 Gy, delivered as 6 fractions given over 2 weeks (5 Gy per fraction). Hydroxychloroquine was given as 200 mg orally b.d. from 7 days prior to radiotherapy until disease progression. The primary endpoint was 1-year overall survival (OS). Secondary endpoints included progression-free survival (PFS), quality of life, and toxicity. RESULTS: Fifty-four patients with a median age of 75 were randomized between May 2013 and October 2016. The trial was stopped early in 2016. One-year OS was 20.3% (95% confidence interval [CI] 8.2-36.0) hydroxychloroquine group, and 41.2% (95% CI 18.6-62.6) radiotherapy alone, with a median survival of 7.9 and 11.5 months, respectively. The corresponding 6-month PFS was 35.3% (95% CI 19.3-51.7) and 29.4% (95% CI 10.7-51.1). The outcome in the control arm was better than expected and the excess of deaths in the hydroxychloroquine group appeared unrelated to cancer. There were more grade 3-5 events in the hydroxychloroquine group (60.0%) versus radiotherapy alone (38.9%) without any clear common causation. CONCLUSIONS: Hydroxychloroquine with short-course radiotherapy did not improve survival compared to radiotherapy alone in elderly patients with glioblastoma.
ABSTRACT
UNLABELLED: This study tested the principle that (68)Ga-DOTATATE PET/CT may be used to select children with primary refractory or relapsed high-risk neuroblastoma for treatment with (177)Lu-DOTATATE and evaluated whether this is a viable therapeutic option for those children. METHODS: Between 2008 and 2010, 8 children with relapsed or refractory high-risk neuroblastoma were studied with (68)Ga-DOTATATE PET/CT. The criterion of eligibility for (177)Lu-DOTATATE therapy was uptake on the diagnostic scan equal to or higher than that of the liver. RESULTS: Of the 8 children imaged, 6 had abnormally high uptake on the (68)Ga-DOTATATE PET/CT scan and proceeded to treatment. Patients received 2 or 3 administrations of (177)Lu-DOTATATE at a median interval of 9 wk and a median administered activity of 7.3 GBq. Of the 6 children treated, 5 had stable disease by the response evaluation criteria in solid tumors (RECIST). Of these 5 children, 2 had an initial metabolic response and reduction in the size of their lesions, and 1 patient had a persistent partial metabolic response and reduction in size of the lesions on CT, although the disease was stable by RECIST. One had progressive disease. Three children had grade 3 and 1 child had grade 4 thrombocytopenia. No significant renal toxicity has been seen. CONCLUSION: (68)Ga-DOTATATE can be used to image children with neuroblastoma and identify those suitable for molecular radiotherapy with (177)Lu-DOTATATE. We have shown, for what is to our knowledge the first time, that treatment with (177)Lu-DOTATATE is safe and feasible in children with relapsed or primary refractory high-risk neuroblastoma. We plan to evaluate this approach formally in a phase I-II clinical trial.
