TY - JOUR
T1 - A novel trial of topotecan, ifosfamide, and carboplatin (TIC) in children with recurrent solid tumors
AU - Radhakrishnan, Kavita
AU - Lee, Alice
AU - Harrison, Lauren A.
AU - Morris, Erin
AU - Shen, Violet
AU - Gates, Laura
AU - Wells, Robert J.
AU - Wolff, Johannes E.
AU - Garvin, James H.
AU - Cairo, Mitchell S.
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Background: Ifosfamide, carboplatin, and etoposide (ICE) in children with refractory or recurrent solid tumors and lymphomas has resulted in good overall response rates (ORR). Etoposide, a topoisomerase-II inhibitor, however, has been associated with a significant increase in secondary leukemia. The rationale for substituting topotecan, a topoisomerase-I inhibitor, for etoposide in this regimen, a topoisomerase-II inhibitor, includes its limited toxicity profile and decreased leukemogenicity. Furthermore, topotecan in combination with both alkylators and platinating agents are additive and/or synergistic against a variety of solid tumors. Procedure: Patients with relapsed/refractory solid tumors received ifosfamide (9g/m2) and carboplatin (area under the curve: 3mg/ml/min). Topotecan was also administered at 0.5mg/m2/day×3 days (N=12) and in a small cohort (N=3) at 0.75mg/m2/day. Results: Fifteen patients were entered onto study. Two patients developed seizures/encephalitis secondary to ifosfamide. One patient had dose-limiting thrombocytopenia secondary to TIC that resolved with supportive care. Patients received a median of three cycles (1-3) of TIC. Of the 14 evaluable patients for response, 4/14 had a complete response (CR), 2/14 had a partial response (PR), and 1/14 patients had stable disease (SD). The ORR (CR+PR) was 43%. Conclusion: TIC chemotherapy is feasible and tolerable in children and adolescents with refractory/recurrent solid tumors and lymphomas and results in a 43% excellent ORR in this poor-risk group of patients. A larger cohort of patients, especially in Wilms tumor and central nervous system (CNS) tumors, should be studied in the future to attempt to confirm these preliminary findings.
AB - Background: Ifosfamide, carboplatin, and etoposide (ICE) in children with refractory or recurrent solid tumors and lymphomas has resulted in good overall response rates (ORR). Etoposide, a topoisomerase-II inhibitor, however, has been associated with a significant increase in secondary leukemia. The rationale for substituting topotecan, a topoisomerase-I inhibitor, for etoposide in this regimen, a topoisomerase-II inhibitor, includes its limited toxicity profile and decreased leukemogenicity. Furthermore, topotecan in combination with both alkylators and platinating agents are additive and/or synergistic against a variety of solid tumors. Procedure: Patients with relapsed/refractory solid tumors received ifosfamide (9g/m2) and carboplatin (area under the curve: 3mg/ml/min). Topotecan was also administered at 0.5mg/m2/day×3 days (N=12) and in a small cohort (N=3) at 0.75mg/m2/day. Results: Fifteen patients were entered onto study. Two patients developed seizures/encephalitis secondary to ifosfamide. One patient had dose-limiting thrombocytopenia secondary to TIC that resolved with supportive care. Patients received a median of three cycles (1-3) of TIC. Of the 14 evaluable patients for response, 4/14 had a complete response (CR), 2/14 had a partial response (PR), and 1/14 patients had stable disease (SD). The ORR (CR+PR) was 43%. Conclusion: TIC chemotherapy is feasible and tolerable in children and adolescents with refractory/recurrent solid tumors and lymphomas and results in a 43% excellent ORR in this poor-risk group of patients. A larger cohort of patients, especially in Wilms tumor and central nervous system (CNS) tumors, should be studied in the future to attempt to confirm these preliminary findings.
KW - Lymphoma
KW - Pediatrics
KW - Refractory/recurrent solid tumor
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U2 - 10.1002/pbc.25309
DO - 10.1002/pbc.25309
M3 - Article
C2 - 25382188
AN - SCOPUS:84927562186
SN - 1545-5009
VL - 62
SP - 274
EP - 278
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 2
ER -