Outcome of patients with sarcoma and other mesenchymal tumours participating in phase I trials: a subset analysis of a European Phase I database

Cassier, Philippe; Polivka, Valentine; Judson, Ian; Soria, Jean‐Charles; Penel, Nicolas; Marsoni, Silvia; Verweij, Jaap; Schellens, Jan H.M.; Morales-Bárrera, Rafael; Schöffski, Patrick; Voest, Emile E.; Gomez‐Roca, Carlos; Evans, T.R. Jeffry; Plummer, Ruth; Gallerani, Elisa; Kaye, Stan B.; Olmos, David

doi:10.1093/annonc/mdu108

Cited by 20 publications

(19 citation statements)

References 16 publications

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“…In this study, the safety profiles of investigational drugs were in agreement with the previously reported outcomes in patients with other malignancies [28, 29]. Two GIST patients (9.5 %) were withdrawn from a phase I clinical trial because of toxicity or treatment refusal, and there were no treatment-related deaths.…”

Section: Discussionsupporting

confidence: 89%

“…We recognized neither PR nor CR; however, in the third-line of sarcoma, responses were rarely observed in the early clinical trials. These results suggest that GIST patients may have some clinical benefits from participating in all comer phase I clinical trials with significant safety as previously reported in other malignancies [19–21, 23–28] and that phase I clinical trials may be one of treatment options for patients with GISTs refractory to the standard therapy.…”

Section: Discussionsupporting

confidence: 78%

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Clinical outcomes of patients with gastrointestinal stromal tumor in phase I clinical trials

et al. 2016

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BackgroundThe prognosis of patients with gastrointestinal stromal tumor (GIST) after the failure of standard therapies is poor with supportive care alone. Guidelines recommend clinical trials, and patients with good performance status following standard therapies are often eligible for phase I clinical trials of investigational agents; however, there are no detailed reports on the clinical outcomes of GIST patients enrolled in these trials.MethodsWe retrospectively reviewed the clinical outcomes of 21 consecutive GIST patients who were enrolled in one or more phase I clinical trials at a single center between March 2009 and November 2014.ResultsThe median age was 57 years, and the median number of previous lines of standard chemotherapy was three. Chemotherapy before enrollment in a phase I clinical trial included imatinib, sunitinib, and regorafenib in 100, 95, and 43 % of patients, respectively. None of the patients achieved objective response. Ten patients (47.6 %) were determined to be stable according to the Response Evaluation Criteria in Solid Tumors; four of them (19.0 %) maintained their status for more than 24 weeks. Four patients achieved partial response according to the Choi criteria. No dose-limiting toxicity was observed; however, severe adverse events and grade 3 or higher toxicities were reported in one (4.8 %) and two patients (9.5 %), respectively. Although no treatment-related deaths occurred, one patient (4.8 %) died within 30 days after the last drug administration because of disease progression. The median progression-free survival was 1.9 months, and the median overall survival time has not been reached.ConclusionsData suggested that phase I clinical trials were feasible and may provide prognostic benefits to GIST patients after standard therapies, indicating that enrollment in these studies may provide a treatment option for these patients.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 78%

Clinical outcomes of patients with gastrointestinal stromal tumor in phase I clinical trials

et al. 2016

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“…Unlike carcinomas derived from epithelial tissues, sarcomas comprise a heterogeneous group of malignancies of mesenchymal origin [1, 2]. There are 15,000 new sarcoma cases per year in the United States, consisting of 12,000 cases of soft tissue sarcoma and 3,000 cases of bone sarcomas [1].…”

Section: Introductionmentioning

confidence: 99%

Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR

Borgatti

Koopmeiners

Sarver

et al. 2017

Molecular Cancer Therapeutics

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Sarcomas differ from carcinomas in their mesenchymal origin. Therapeutic advancements have come slowly so alternative drugs and models are urgently needed. These studies report a new drug for sarcomas that simultaneously targets both tumor and tumor neovasculature. eBAT is a bispecific angiotoxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epidermal growth factor (EGF) and the amino terminal fragment (ATF) of urokinase. Here, we study the drug in an in vivo “ontarget” companion dog trial since eBAT effectively kills canine hemangiosarcoma (HSA) and human sarcoma cells in vitro. We reasoned the model has value due to the common occurrence of spontaneous sarcomas in dogs and a limited lifespan allowing for rapid accrual and data collection. Splenectomized dogs with minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin in an adaptive dose-finding, phase I–II study of 23 dogs with spontaneous, stage I–II, splenic HSA. eBAT improved 6-month survival from <40% in a comparison population to ~70% in dogs treated at a biologically active dose (50 μg/kg). Six dogs were long-term survivors, living >450 days. eBAT abated expected toxicity associated with EGFR-targeting, a finding supported by mouse studies. Urokinase plasminogen activator receptor (uPAR) and EGFR are targets for human sarcomas, so thorough evaluation is crucial for validation of the dog model. Thus, we validated these markers for human sarcoma targeting in the study of 212 human and 97 canine sarcoma samples. Our results support further translation of eBAT for human patients with sarcomas and perhaps other EGFR-expressing malignancies.

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“…Cassier et al . of the French Sarcoma Group (Groupe Sarcome Français – Groupe d’Etude des Tumeurs Osseuses [GSF-GETO]) analyzed the Conticabase database and found that adjuvant radiation for extremity and trunk wall ALT/WDLS led to a 5-year local relapse-free survival of 98.3% versus 80.3% without radiation therapy (hazard ratio 0.26) 34 . Although a local control benefit may be achieved with adjuvant radiation therapy, there is no expected survival benefit given that these tumors do not metastasize.…”

Section: Radiation Therapymentioning

confidence: 99%

Recent advances in the management of liposarcoma

Nassif

Tseng

Borges³

et al. 2016

F1000Res

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Liposarcoma is the most common soft tissue sarcoma. With its various subtypes, the natural history of this disease can vary significantly from a locally recurrent tumor to a highly malignant one carrying a poor prognosis. Progress in the understanding of the specific molecular abnormalities in liposarcoma provides greater opportunity for new treatment modalities. Although surgical resection and radiation therapy remain the keystones for the management of primary liposarcoma, the inclusion of novel agents that target known abnormalities in advanced liposarcoma enhances the potential for improved outcomes.

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Outcome of patients with sarcoma and other mesenchymal tumours participating in phase I trials: a subset analysis of a European Phase I database

Cited by 20 publications

References 16 publications

Clinical outcomes of patients with gastrointestinal stromal tumor in phase I clinical trials

Clinical outcomes of patients with gastrointestinal stromal tumor in phase I clinical trials

Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR

Recent advances in the management of liposarcoma

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