TY - JOUR
T1 - Doxorubicin in combination with cisplatin, 5-flourouracil, and vincristine is feasible and effective in unresectable hepatoblastoma
T2 - A Children's Oncology Group study
AU - Katzenstein, Howard M.
AU - Malogolowkin, Marcio H.
AU - Krailo, Mark D.
AU - Piao, Jin
AU - Towbin, Alexander J.
AU - McCarville, M. Beth
AU - Tiao, Gregory M.
AU - Dunn, Stephen P.
AU - Langham, Max R.
AU - McGahren, Eugene D.
AU - Finegold, Milton J.
AU - Ranganathan, Sarangarajan
AU - Weldon, Christopher B.
AU - Thompson, Patrick A.
AU - Trobaugh-Lotrario, Angela D.
AU - O’Neill, Allison F.
AU - Furman, Wayne L.
AU - Chung, Nadia
AU - Randazzo, Jessica
AU - Rodriguez-Galindo, Carlos
AU - Meyers, Rebecka L.
N1 - Funding Information:
This research was supported by Imaging and Radiation Oncology Core Rhode Island (formerly Quality Assurance Review Center) grant U10 CA29511, National Clinical Trials Network Operations Center grant U10CA180886, and Statistics and Data Center grant U10CA180899 from the National Cancer Institute of the National Institutes of Health (Bethesda, Maryland) and by St. Baldrick's Foundation (Monrovia, California). A complete listing of grant support for research conducted by the Children's Cancer Group and the Pediatric Oncology Group before the initiation of the Children's Oncology Group grant in 2003 is available online at http://www.childrensoncologygroup.org/admin/grantinfo.htm .
Funding Information:
Howard M. Katzenstein is employed by EMD Serono, a division of Merck KGaA; the work was performed before this employment. Mark D. Krailo reports personal fees from Merck Sharpe & Dohme outside the submitted work. Alexander J. Towbin reports grants from the Cystic Fibrosis Foundation, Guerget, and Siemens and reports royalties from Applied Radiology and Elsevier outside the submitted work. Allison F. O’Neill reports travel reimbursements for biannual Children's Oncology Group meetings. The other authors made no disclosures.
Publisher Copyright:
© 2021 American Cancer Society
PY - 2021
Y1 - 2021
N2 - Background: The Children's Oncology Group (COG) adopted cisplatin, 5-flourouracil, and vincristine (C5V) as standard therapy after the INT-0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease. Methods: In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility. Results: One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%-97%) for cisplatin, 96% (95% CI, 94%-97%) for 5-fluorouracil, 95% (95% CI, 93%-97%) for doxorubicin, and 90% (95% CI, 87%-93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5-year event-free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%-93%) and 95% (95% CI, 87%-98%), respectively. Conclusions: The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials.
AB - Background: The Children's Oncology Group (COG) adopted cisplatin, 5-flourouracil, and vincristine (C5V) as standard therapy after the INT-0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease. Methods: In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility. Results: One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%-97%) for cisplatin, 96% (95% CI, 94%-97%) for 5-fluorouracil, 95% (95% CI, 93%-97%) for doxorubicin, and 90% (95% CI, 87%-93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5-year event-free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%-93%) and 95% (95% CI, 87%-98%), respectively. Conclusions: The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials.
KW - cisplatin
KW - doxorubicin
KW - hepatoblastoma
KW - pediatric liver transplant
KW - pediatric liver tumor
KW - Pretreatment Extent of Disease (PRETEXT)
KW - toxicity
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U2 - 10.1002/cncr.34014
DO - 10.1002/cncr.34014
M3 - Article
C2 - 34762296
AN - SCOPUS:85118852397
JO - Cancer
JF - Cancer
SN - 0008-543X
ER -