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. 2020 May 10;38(14):1558-1568.
doi: 10.1200/JCO.19.01265. Epub 2020 Mar 5.

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

Najat C Daw  1 , Yueh-Yun Chi  2 , John A Kalapurakal  3 , Yeonil Kim  2 , Fredric A Hoffer  4 , James I Geller  5 , Elizabeth J Perlman  6 , Peter F Ehrlich  7 , Elizabeth A Mullen  8 , Anne B Warwick  9 , Paul E Grundy  10 , Arnold C Paulino  11 , Eric Gratias  12 , Deborah Ward  13 , James R Anderson  14 , Geetika Khanna  15 , Brett Tornwall  2 , Conrad V Fernandez  16 , Jeffrey S Dome  17 ; AREN0321 Study Committee
Affiliations

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

Najat C Daw et al. J Clin Oncol. .

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.

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Figures

FIG 1.
FIG 1.
Study flow diagram. Patients enrolled in AREN0321 by stage and response to treatment with vincristine and irinotecan (VI) window. (*)Although a partial response was achieved, the treating physician elected to treat with revised regimen UH1.
FIG 2.
FIG 2.
(A) Event-free survival (EFS), (B) overall survival (OS), and (C) relapse-free survival (RFS) of patients with stage II to IV diffuse anaplastic Wilms tumor according to study.
FIG A1.
FIG A1.
(A) Event-free survival (EFS) and (B) overall survival (OS) of 66 patients with stage II to IV diffuse anaplastic Wilms tumor treated in AREN0321 according to disease stage.
See this image and copyright information in PMC

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