The effect of gastrectomy on regorafenib exposure and progression-free survival in patients with advanced gastrointestinal stromal tumours

Contains fulltext : 208932.pdf (publisher's version ) (Open Access)AIMS: We investigated whether major gastrectomy influences the plasma exposure of regorafenib and treatment outcome. METHODS: Efficacy and pharmacokinetic data from 133 gastrointestinal stromal tumour patients included in a phase III trial were analysed. Patients were subdivided into 2 groups according to the extent of the gastrectomy (no/nonsignificant gastrectomy and major gastrectomy). Progression-free survival (PFS) on regorafenib was measured and regorafenib and its pharmacological active metabolites plasma exposure were measured. RESULTS: A total of 133 patient were included, of whom 27 underwent major gastrectomy. In patients with no/nonsignificant gastrectomy the median PFS was 145 (interquartile range 43-281) days. The PFS in patients with a major gastrectomy was 172 (interquartile range 57-280) days. Regorafenib pharmacokinetic samples were collected in 80 patients of which 19 patients with a major gastrectomy and 61 patients with no/nonsignificant gastric surgery. The average +/- standard deviation total concentration of regorafenib including the metabolites M-2 and M-5 was 6.9 +/- 1.53 mumol/L and 6.7 +/- 1.56 mumol/L in patient with major gastrectomy and no/nonsignificant gastrectomy respectively. CONCLUSION: Our study shows that major gastrectomy did not influence plasma exposure of regorafenib and metabolites. In addition, no difference in PFS between the subgroups was seen

Imatinib Mesylate: Past Successes and Future Challenges in the Treatment of Gastrointestinal Stromal Tumors

Just over a decade ago, gastrointestinal tumours were a poorly understood mesenchymal neoplasm unsuccessfully treated with chemotherapy. Cytotoxic therapy for advanced disease yielded response rates of 10% and median survival of just 18 months. However, the discovery of KIT and platelet derived growth factor receptor alpha (PDGFRA) mutations as oncogenic drivers of most gastrointestinal tumours, paved the way for targeted therapy. Imatinib mesylate, a tyrosine kinase inhibitor, produces a clinical benefit rate (complete response, partial response, and stable disease) of more than 80% in metastatic setting and a median survival of 57 months. Imatinib is now also approved in adult patients following resection of KIT-positive GIST. Major insights into the mechanism of action of imatinib, unique pharmacokinetics, drug resistance, and management of low grade but chronic adverse effects continue to be made

Primary Extra-gastrointestinal Stromal Tumor of Retroperitoneum

Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. More rarely neoplasms with histology and immunohistochemistry similar to GISTs may occur outside the gastrointestinal tract (omentum, mesentery and retroperitoneum) and are so-called Extra-gastrointestinal Stromal Tumors (EGISTs). EGISTs arising in the retroperitoneum are extremely rare: to date, only 58 cases have been reported in the literature. Case Report We herein report a case of a primary EGIST of the retroperitoneum surgically treated. The pre-operative radiological evaluation showed a retroperitoneal mass, placed in left paravertebral region. Results Morphological and immunohistochemical features led to a diagnosis of extra-gastrointestinal stromal tumor (intermediate-low risk form). Conclusions As a result of the rarity of reports of primary EGISTs of retroperitoneum we need to analyze the data of reported cases in order to gain a better understanding about the pathogenesis, prognosis and optimal treatment of this disease

Ultra-rare sarcomas: a consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities

Background Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies.Methods The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan.Results It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately <= 1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types.conclusions Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.Experimentele farmacotherapi

The influence of gastrointestinal resection on sunitinib exposure in GIST patients

Personalised Therapeutic