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.