Activity of Vincristine and Irinotecan in Diffuse Anaplastic Wilms Tumor and Therapy Outcomes of Stage II to IV Disease: Results of the Children’s Oncology Group AREN0321 Study

Abstract

PURPOSE AREN0321 evaluated the activity of vincristine and irinotecan (VI) in patients with newly diagnosed diffuse anaplastic Wilms tumor (DAWT) and whether a regimen containing carboplatin (regimen UH1) in addition to regimen I agents used in the National Wilms Tumor Study 5 (NWTS-5; vincristine, doxorubicin, cyclophosphamide, and etoposide plus radiotherapy) would improve patient outcomes. PATIENTS AND METHODS Patients with stage II to IV DAWT without measurable disease received regimen UH1. Patients with stage IV measurable disease were eligible to receive VI (vincristine, 1.5 mg/m2 per day intravenously on days 1 and 8; irinotecan, 20 mg/m2 per day intravenously on days 1-5 and 8-12 of a 21-day cycle) in an upfront window; those with complete (CR) or partial response (PR) had VI incorporated into regimen UH1 (regimen UH2). The study was designed to detect improvement in outcomes of patients with stage II to IV DAWT compared with historical controls treated with regimen I. RESULTS Sixty-six eligible patients were enrolled. Of 14 patients with stage IV measurable disease who received VI, 11 (79%) achieved CR (n = 1) or PR (n = 10) after 2 cycles. Doses of doxorubicin, cyclophosphamide, and etoposide were reduced midstudy because of nonhematologic toxicity. Four patients (6%) died as a result of toxicity. Four-year event-free survival, relapse-free survival, and overall survival rates were 67.7% (95% CI, 55.9% to 79.4%), 72.9% (95% CI, 61.5% to 84.4%), and 73.7% (95% CI, 62.7% to 84.8%), respectively, compared with 57.5% (95% CI, 47.6% to 67.4%; P = .26), 57.5% (95% CI, 47.6% to 67.4%; P = .048), and 59.2% (95% CI, 49.4% to 69.0%; P = .08), respectively, in NWTS-5. CONCLUSION VI produced a high response rate in patients with metastatic DAWT. AREN0321 treatment seemed to improve outcomes for patients with stage II to IV DAWT compared with NWTS-5, but with increased toxicity. The UH2 regimen warrants further investigation with modifications to reduce toxicity.

Prognostic Factors for Wilms Tumor Recurrence: A Review of the Literature

“…The NWTS-5 study did not observe an increased relapse rate among stage IV FHWT, compared to localized FHWT, stratified by 1q gain [29]. However, inferior EFS was observed in case of stage IV anaplastic histology WT (AHWT) (Table 2) [43][44][45]. AIEOP TW2003 and UKW3 reported similar findings: EFS was not different between stage I and stage IV patients when adjusted for tumor histology [5,25] (Table 3).…”

Irinotecan Plus Doxorubicin Hydrochloride Liposomes for Relapsed or Refractory Wilms Tumor

“…Studies have revealed that doxorubicin-induced heart failure (HF) occurs in 3%–5% of patients treated with 400 mg/m 2 doxorubicin ( 28 ). Cumulative doses of doxorubicin in patients with WT in COG and SIOP studies were no greater than 250 mg/m 2 ( 22 , 29 ). Doxorubicin hydrochloride liposomes are a novel formulation of doxorubicin encapsulated in polyethylene glycol-coated liposomes, and their pharmacokinetics (PK) is markedly different from that of doxorubicin.…”

Болалардаги Буйрак Ўсмалари Ҳақида Умумий Маълумотлар (Нефробластома)

“…Wilms tumor is the most frequent tumor of the kidney in infants and children. The incidence of Wilms tumor is 8.2 cases for every 1 million children younger than 15 years, or one case per 10,000 infants [1]. Approximately 650 cases of Wilms tumor are diagnosed in the United States each year.…”

“…The risk is lowest for KTS splice site mutations (1 of 27 cases, 4%). Bilateral Wilms tumor was more common in cases with WT1-truncating mutations (9 of 14 cases) than in cases with WT1 missense mutations (3 of 27 cases) [1,3].…”

“…Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50% [1]. For children younger than 15 years with Wilms tumor, the 5-year survival rate has increased over the same time from 74% to 88% [12].…”