Ifosfamide-Induced Neurotoxicity in Children with Solid Tumors: A Seven Year Retrospective Analysis of Incidence and Risk Factors.

Background: Patients with cancer treated with the pro-drug ifosfamide may experience drug-induced neurotoxicity. Ifosfamide-induced neurotoxicity (IIN) is well described in the adult literature, but there is limited knowledge about this toxicity in pediatrics, especially in children with solid tumors. Methods: In this retrospective descriptive study, the author reviewed 7 years of clinical data regarding patients with solid tumors who received ifosfamide at a large, urban pediatric medical center. The author used descriptive statistics and logistic regression to describe the incidence of IIN and identify demographic and clinical factors most likely to be associated with the toxicity. Results: In a sample of 169 pediatric patients who received ifosfamide between 2011 and 2018, 13% developed symptoms of IIN. The author identified ifosfamide doses >2,000 mg/m2 to be a risk factor for IIN in the study sample (OR 17.82; 95 CI [2.17, 146.18]; p = .0073) and cited other variables as possible risk factors, though each could be linked to participants' ifosfamide exposure. Discussion: This study is the largest to describe IIN specifically in the pediatric solid tumor population. The study findings suggest the pattern of toxicity observed in adult patients should not be assumed in children. The author identified one risk factor that may predispose children to develop IIN and recommends further attention be paid to this toxicity in the pediatric population.

Docetaxel, bevacizumab, and gemcitabine for very high risk sarcomas in adolescents and young adults: A single-center experience.

BACKGROUND: Adolescent and young adult (AYA) patients with very high risk sarcomas have poor outcomes and are in need of novel therapies. PROCEDURE: From January 2005 to February 2016, we retrospectively identified all AYA patients with relapsed or metastatic high-grade sarcomas, who were treated with at least one cycle of docetaxel (T), bevacizumab (A), and gemcitabine (G) (TAG ; T = 100 mg/m2 Day 8, A = 15 mg/kg Day 1, G = 1,000 mg/m2 Days 1 and 8). RESULTS: Fourteen patients, median age of 20 (15-30), received a total of 80 cycles of TAG, and were followed for a median of 83 months. Diagnosis included osteosarcoma (OST; 8), Ewing sarcoma (3), and soft tissue sarcoma (3). Five of 14 patients achieved clinical remission (CR), 3 had partial responses (PR), 3 had stable disease (SD), and 3 had progressive disease (PD). The median progression-free survival and overall survival were 7 and 19 months, respectively. The objective response rate (CR + PR) and tumor control rate (CR + PR + SD) were 57% and 79%, respectively, with two patients alive after 5 years; toxicities included thrombocytopenia, neutropenia, and capillary leak syndrome. CONCLUSIONS: Our study builds on previous studies utilizing TAG in adult leiomyosarcoma (LMS) by focusing on AYA, non-LMS sarcomas, especially OST. Our experience suggests that TAG is well tolerated and has activity in very high risk sarcomas in AYA.