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).

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.

Treatment of childhood astrocytomas with irinotecan and cisplatin.

BACKGROUND: Previously we described the outcome of children with spinal cord astrocytoma treated with irinotecan and cisplatin (I/C). We here report the review of the initial institutional experience using this combination for children with low-grade glioma (LGG). PROCEDURE: I/C chemotherapy consisted of weekly cisplatin (30 mg/m2) and irinotecan (50-65 mg/m2) for a total maximum of 16 doses, administered in an outpatient basis. RESULTS: Between November 2002 and December 2009, 46 children (median age 6.3 years; range 0.3-17.7) with glioma were treated. We here report the cohort of 31 patients with LGG. Patients received a median of 16 cycles of I/C (range 8-16). The overall objective response [complete response (CR) + partial response (PR)] and disease control (CR + PR + stable disease) rates to I/C treatment were 6.5% [95% confidence interval (CI), 0.8-21.4%] and 93.5% (95% CI 78.6-99.2%), respectively. Disease control persisted for a median of 65 months. Toxicity was predominantly myelosuppression only seen in heavily pretreated patients. Survival analysis shows 5-year event-free survival (EFS) of 54% and 5-year overall survival (OS) of 80%. CONCLUSION: I/C chemotherapy produced disease control and clinical improvement in a majority of children with low-grade glioma, with manageable toxicity.