GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS)

Abstract

Background:First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients.Methods:This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR patients (metastatic, axial-pelvic primaries or bone marrow micrometastasis) received 2 window cycles of G/D. Patients with an objective response (OR) to G/D received 12 monthly cycles of G/D after completion of mP6. The primary end point was the OR rate to the G/D window phase and the event-free survival (EFS) and overall survival (OS) for all patients. The study is registered at ClinicalTrials.gov (identifier: NCT00006734).Results:Forty-three patients were enroled, median age 17 years (range, 3–40). After a median follow-up of 43.4 months, the 5-year OS rate is 55.0% (95% CI, 41–74%) with an EFS of 50.0% (95% CI, 36–68%). The 5-year OS and EFS rates for standard risk (SR) patients was 76.0% (95% CI, 57–100%) and 71.0% (CI, 54–94%); for HR 36.0% (CI, 20–65%) and 29.0% (CI, 15–56%). Twelve of 17 (70.6%) high-risk (HR) patients showed an OR (7 PR and 5 SD) to G/D window therapy. The 5-year OS rate for patients ⩽18 years of age was 74.0% (CI, 56–97%) and 31.0% for >18 years (95% CI, 15–66%), P<0.001. Grade 4 adverse events during mP6 occurred in 28/39 of patients (72%) and did not correlate with age. Multivariate survival analyses with <18 vs ⩾18 and risk groups significant differences, P<0.00001. Using a Cox model for OS, both age and risk group were statistically significant (P=0.0011 and P=0.0065, respectively).Conclusions:Age at diagnosis is an independent prognostic factor superior to the presence of metastases with 18 years as the strongest cut-off. The mP6 regimen provided survival curves that plateau at 3 years and G/D produced significant responses in HR-ES that is worth further exploring.

Cranial Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumors: A Retrospective Study Focused on Prognostic Factors and Long-Term Outcomes

“…The same results were achieved for maximum tumor diameter, tumor type, brain invasion, and bone invasion. However, a recent study has reported that age was an independent prognostic factor for the prognosis of patients (12).…”

Prognostic value of patient‐derived xenograft engraftment in pediatric sarcomas

“…The most frequently occurring are Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma, altogether representing 13% of all malignant tumors in patients younger than 14 years, and up to 18% of all tumors among patients between 15 and 19 years [2][3][4]. With up-to-date treatment modalities, the 5-year survival rates have improved in the last decade to 79% for Ewing sarcoma, 73% for osteosarcoma, and 70% for rhabdomyosarcoma [5][6][7]. Unfortunately, intensive and multimodal treatments currently used in pediatric sarcomas have topped their efficacy [1,8,9].…”

Phase II trial of gemcitabine and nab‐paclitaxel in patients with recurrent Ewing sarcoma: A report from the National Pediatric Cancer Foundation

“…However, in prospective multi‐institutional trials for relapsed Ewing sarcoma, the response rate for 80 total patients was only 12% 8,9 . In the one study involving newly diagnosed patients with Ewing sarcoma, two cycles of GEM/DOC were used as an upfront window to treat 17 evaluable higher‐risk patients 10 . Although 41% of patients had a partial response, 29% experienced progression during this window.…”