Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas.

BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution. RESULTS: Sixteen patients (median age 13.5 years, range 3-19 years) received 53 cycles of gemcitabine/nab-paclitaxel. Twenty-nine cycles (55%) resulted in ≥Grade 3 toxicity, with nonhematologic Grade ≥3 toxicities occurring in only eight of 53 cycles (15%). Patients received red blood cell and platelet transfusions in 23% and 4% of cycles, respectively. Grade ≥3 infectious toxicities occurred in 4% of cycles. Of 14 patients with measurable disease, there were no complete responses (CR), one partial response (PR; 7%), and six patients (43%) with stable disease (SD; median SD: 4.5 months, range: 2-19 months). In total, 31% of the patients derived clinical benefit (CR + PR + SD ≥ 4 months). Median time to progression was 72 days with a 4-month progression-free survival of 31% ± 12% and 1-year overall survival of 19% ± 10%. With a median follow-up for all 16 patients of 21 months from the first treatment with gemcitabine/nab-paclitaxel, one (6%) remains alive with disease. CONCLUSIONS: Gemcitabine/nab-paclitaxel is a relatively safe regimen with mainly hematologic toxicities. It offers a well-tolerated, palliative option providing clinical benefit in a subset of patients. A phase I trial of this combination is underway.

Yield of screening echocardiograms during pediatric follow-up in survivors treated with anthracyclines and cardiotoxic radiation.

BACKGROUND: Guidelines published by the Children's Oncology Group recommend screening echocardiograms for childhood cancer survivors exposed to anthracyclines and/or cardiotoxic radiation. This study aims to assess risk factors for cardiac late effects while evaluating the overall yield of screening echocardiograms. PROCEDURE: Demographics, exposures, and echocardiogram results were abstracted from the medical records of survivors diagnosed at ≤ 21 years old and ≥ 2 years off therapy who were exposed to anthracyclines and/or potentially cardiotoxic radiotherapy. Descriptive statistics and logistic regressions were performed and the yield of screening echocardiograms was calculated. RESULTS: Of 853 patients, 1,728 screening echocardiograms were performed, and 37 patients had an abnormal echocardiogram (overall yield 2.1%). Yields were only somewhat higher in more frequently screened patients. Risk factors for an abnormal result included anthracycline dose of ≥300 mg/m2 (adjusted odds ratio [aOR] 3.1; 95% confidence interval [CI]: 1.3-7.2; P < 0.01) with a synergist relationship in patients who also received radiation doses ≥30 Gy (aOR 7.0; 95% CI: 1.6-31.9; P = 0.01), as well as autologous bone marrow transplant (OR 3.3; 95% CI: 1.3-8.5; P = 0.01). Sex, race, age at diagnosis, and cyclophosphamide exposure were not statistically significant risk factors, and no patient receiving <100 mg/m2 anthracycline dose without concomitant radiation had an abnormal echocardiogram. CONCLUSIONS: Dose-dependent and synergist anthracycline and cardiotoxic radiotherapy risks for developing cardiomyopathy were confirmed. However, previously identified risk factors including female sex, black race, and early age at diagnosis were not replicated in this cohort. The yields showed weak correlation across frequency categories. Echocardiographic screening recommendations for low-risk pediatric patients may warrant re-evaluation.