Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study

Abstract

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%–86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents.

Long-Term Complete Remission of Recurrent Unresectable Thymoma Type B2 under Somatostatin Analogue Treatment. Case Report

“…It has been reported that somatostatin has antiproliferative activity associated with growth factors inhibition, such as insulin-like growth factor-1 and epidermal growth factor, activation of immunity and tumor vessel angiogenesis inhibition. Recently, octreotide Long-Acting Release (LAR) (intramuscular injections of 30 mg/every two weeks) plus prednisolone (0.6 mg/kg/day), for a maximum of 24 weeks, has been evaluated as neoadjuvant treatment in patients with positive octreotide scans in a phase II study [7]. Among 17 patients with primarily unresectable or advanced locally recurrent thymoma (15 cases) or TC, the ORR after 3 months of treatment was 88%, and overall operability after 6 months of treatment was 52%.…”

“…The reported adverse events associated with octreotide are most common hematological and gastrointestinal, and grade 1 or 2. However, fatal pneumonia, probably caused by thymomaassociated immunodeficiency during steroid medication not to octreotide LAR was reported [7].…”

An Overview on Molecular Characterization of Thymic Tumors: Old and New Targets for Clinical Advances

“…Patients with TC display higher serum concentrations of VEGF and b-FGF than patients with TM [ 29 ]. TETs can also express somatostatin receptors (SSTR), providing a rationale for somatostatin’s anti-proliferative effect as a therapeutic option [ 30 , 31 ]. Additionally, mesothelin is expressed with high frequency in TCs and it is potentially targetable [ 32 ].…”

“…SSTRs are expressed in TETs, thus the efficacy of octreotide, a somatostatin analog, with and without prednisone has been investigated by three phase 2 studies [ 30 , 31 , 59 ]. The primary endpoint was the ORR in each study, and was 37%, 31.6%, and 88%, respectively.…”

“…Notably, no responses were reported in TCs. According to these findings, octreotide could be considered a therapeutic option in TMs with SSTR expression at functional imaging [ 30 , 31 , 59 ].…”