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We evaluated the efficacy of gemcitabine and docetaxel chemotherapy (GEM + DOC) in children and adolescents with recurrent or refractory osteosarcoma.Data of 28 patients (20 male, 8 female) who received gemcitabine (675 or 900 mg/m2 on days 1 and 8) and docetaxel (100 mg/m2 on day 8) at Korea Cancer Center Hospital were retrospectively reviewed.Patients (ages 5.0–19.7 years) received a total of 96 courses of chemotherapy (median 3 courses; range, 1–8 courses) and were followed for a median of 14.9 months (range, 0.6–81.4 months). Eleven patients received GEM + DOC after surgery as adjuvant chemotherapy. Seventeen patients received GEM + DOC as palliative therapy, and were eligible for response evaluation; there were three (17.6%) complete response (CR, including two metabolic CR), one (5.9%) partial responses (PR), and three (29.4%) stable disease (SD). The objective response rate (CR + PR) and tumor control rate (CR + PR + SD) were 23.5% and 41.2%, respectively. The median duration of response was 11.2 months (range, 2.8–14.6 months). Dose of gemcitabine (675 or 900 mg/m2) did not influence the response rate. Overall survival at 1-year was 53.6 ± 9.4% and patients who received GEM + DOC as adjuvant chemotherapy fared better than those who received GEM + DOC as palliative therapy (72.7 ± 13.4% vs. 35.3 ± 11.6%, P = 0.006).GEM + DOC showed some activity in osteosarcoma. Better than expected survival after GEM + DOC was seen both in patients with and without surgery. These results may indicate that dose dense combinations of gemcitabine and taxanes (e.g., gemcitabine + nab-paclitaxel) should be investigated in bone sarcomas. Pediatr Blood Cancer 2014; 61:1376–1381. © 2014 Wiley Periodicals, Inc.