Introduction
Wilms tumor is an embryonal tumor accounts for 90% childhood renal tumor1,2. Medical advances have been greatly improved in the survival rate for the children diagnosed as Wilms tumor in the past decades and exceed over than 85%, but these advances have done nothing with the relapsed or refractory type, and the result is still dismal. Conventional surgery, radiation therapy, and chemotherapy, such as the combination of actinomycin-D and vincristine and/or doxorubicin, are generally used as a standard therapy for Wilms tumor3-6. The salvage regimes, such as the alternating cycle of ICE (ifosfamide, carboplatin, etoposide) and CyCE (cyclophosphamide, carboplatin, etoposide), combined with targeted radiotherapy, has effective but transient response for the treatment of relapsed or refractory Wilms’ tumor7. Limited options are remained to be selected for these types of patients due to the toxicity and side effects on bone marrow, the cardiac function, impaired function of liver and kidney8-10.
Irinotecan, a topoisomerase I inhibitor, is semisynthetic analogue of the camptothecin with modest toxicity on myelosuppression, controllable non-hematologic side effect, and powerful effectivity against the pediatric solid tumor both in xenograft model and patients11-14. A phase I study of irinotecan in pediatric patients recommended that the dose of irinotecan in phase II study was administered as a 60-min iv. infusion daily for 5 days, every 21 days15. Irinotecan combined with other chemotherapy agents (such as vincristine, temozolomide, bevacizumab) has been reported in the clinical application of pediatric solid cancer, including a subset of patients with relapsed Wilms tumor (WT)3,5,16-19. Results of the Children’s Oncology Group AREN0321 Study showed that the overall response rate (ORR) of the VI regimen (irinotecan combined with vincristine) treated for newly diagnosed diffuse anaplastic Wilms tumor (DAWT) was 79%20. For the relapsed or refractory nephroblastoma, several retrospective clinical studies showed that the irinotecan-containing regimens have positive clinical efficacy, with tolerable toxicity19,21-23. Doxorubicin hydrochloride liposome was a novel formulation of doxorubicin encapsulated in polyethylene glycol-coated liposomes and was designed to enhance the efficacy and reduce the dose-limiting toxicities of conventional doxorubicin24. Research showed that the ORR of doxorubicin hydrochloride liposome alone for pediatric sarcoma was 37.5%25. Irinotecan and doxorubicin hydrochloride liposome had low nephrotoxicity, cardiotoxicity, and hematologic toxicity. However, it is still unclear that if patients benefited from irinotecan- Doxorubicin Hydrochloride Liposome regimen in the relapsed or refractory setting. In this study, we describe response and toxicity to irinotecan-liposomal doxorubicin hydrochloride regimens in a collection of patients with relapsed or refractory WT.