Toxicity assessment in children receiving cancer chemotherapy with cyclosporine

Background: During a phase I/II study in pediatric rhabdomyosarcoma patients, cyclosporine (CsA) (6-27 mg/kg/day) was added to standard doses of chemotherapy in an attempt to inhibit the multidrug resistance P-glycoprotein. Chemotherapy consisted of etoposide and ifosfamide (IF/VP cycles), alternating with vincristine, actinomycin D, and cyclophosphamide (VAC cycles). Methods: We compared toxicity during chemotherapy cycles with and without CsA. Results: VAC cycles with CsA were followed by toxicity-related admissions after 93% vs. 38% of the cycles without CsA, p<0.0001. IF/VP cycles with CsA were followed by admissions after 33% vs. 11% of the cycles without CsA, p=0.008. Culture proven sepsis complicated 36% of the VAC cycles with CsA and 6% of the IF/VP cycles with CsA compared to none of the chemotherapy cycles without CsA (VAC: p<0.0001, IF/VP: n.s.). The addition of CsA increased the necessity for platelet and blood transfusions. Conclusions: Addition of CsA to full dose antineoplastic therapy can result in increased chemotherapy toxicity, perhaps by reduction of cytotoxin clearance.