Vincristine/irinotecan/temsirolimus upfront window treatment of high‐risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee

Author:

Thompson Patrick A.1,Malogolowkin Marcio H.2,Furman Wayne L.3,Piao Jin4,Krailo Mark D.4,Chung Nadia5,Brock Lindsay5,Towbin Alexander J.6,McCarville Elizabeth B.3,Finegold Milton J.7,Ranganathan Sarangarajan6,Dunn Stephen P.8,Langham Max R.3,McGahren Eugene D.9,Tiao Gregory M.6,Weldon Christopher B.10,O'Neill Allison F.10,Rodriguez‐Galindo Carlos6,Meyers Rebecka L.11,Katzenstein Howard M.8

Affiliation:

1. North Carolina Children's Hospital and the University of North Carolina Chapel Hill North Carolina USA

2. University of California at Davis Comprehensive Cancer Center Sacramento California USA

3. University of Tennessee Health Science Center and St Jude Children's Research Hospital Memphis Tennessee USA

4. University of Southern California Keck School of Medicine Los Angeles California USA

5. Children's Oncology Group Monrovia California USA

6. Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA

7. Baylor College of Medicine Houston Texas USA

8. Nemours Children's Hospital Wilmington Delaware USA

9. University of Virginia Children's Hospital Charlottesville Virginia USA

10. Dana‐Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center Boston Massachusetts USA

11. Primary Children's Hospital Salt Lake City Utah USA

Abstract

AbstractBackgroundSurvival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high‐risk (HR)/metastatic HB.ProceduresPatients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha‐fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1–5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5‐fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone.ResultsThirty‐six eligible patients enrolled on study. The median age at enrollment was 27 months (range: 7–170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648 ng/mL and the median AFP following two VIT cycles was 19,262 ng/mL. Three‐year event‐free survival was 47% (95% confidence interval [CI]: 30%–62%), while overall survival was 67% (95% CI: 49%–80%).ConclusionVIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.

Publisher

Wiley

Subject

Oncology,Hematology,Pediatrics, Perinatology and Child Health

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