Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study.

Abstract

PURPOSE:

Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.

MATERIALS AND METHODS:

Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2.

RESULTS:

Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%).

CONCLUSION:

TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

• Authors: Loredana Amoroso, Giovanni Erminio, Guy Makin, Andrew D J Pearson, Penelope Brock, Dominique Valteau-Couanet, Victoria Castel, Marlène Pasquet, Genevieve Laureys, Caroline Thomas, Roberto Luksch, Ruth Ladenstein, Riccardo Haupt, Alberto Garaventa, SIOPEN Group
• Journal: Cancer research and treatment (Cancer Res Treat) Vol. 50 Issue 1 Pg. 148-155 (Jan 2018) ISSN: 2005-9256 [Electronic] Korea (South)
• PMID: 28324923 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Topoisomerase I Inhibitors
• Vincristine
• Topotecan
• Doxorubicin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Doxorubicin (administration & dosage)
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Neuroblastoma (drug therapy, pathology)
• Risk Factors
• Topoisomerase I Inhibitors (administration & dosage)
• Topotecan (administration & dosage)
• Vincristine (administration & dosage)