Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial.

Abstract

BACKGROUND:

Sunitinib is approved for treatment of adults with imatinib-resistant gastrointestinal stromal tumor (GIST) or imatinib intolerance.

METHODS:

This single-arm, multicenter, multinational phase I/II clinical trial (NCT01396148) enrolled eligible patients aged 6 to < 18 years with advanced, unresectable GIST with non-mutant KIT, or who demonstrated disease progression or intolerance to imatinib. Patients received sunitinib 15 mg/m2 per day, 4-weeks-on/2-weeks-off (schedule 4/2), for ≤ 18 cycles over 24 months. Intra-patient dose escalation to 22.5 and subsequently 30 mg/m2 were permitted based on individual patient tolerability and supported by real-time pharmacokinetics (PK). Primary objective was PK characterization. Secondary objectives included safety, antitumor activity and PK/pharmacodynamic relationships.

RESULTS:

Six patients were enrolled with median (range) age of 14 (13-16) years. All six patients completed at least three treatment cycles, with one completing all 18 cycles. Five patients had a dose increase to 22.5 mg/m2; two of them had a further dose increase to 30 mg/m2. The average daily dose at cycle 3 was 21.1 mg/m2 (n = 6). Steady-state plasma concentrations were reached by day 15, cycle 1. No tumor responses were observed, but three patients had stabilization of the disease (50%). Median progression-free survival was 5.8 months (95% CI 2.3-not reached). There were no serious adverse events.

CONCLUSIONS:

The tolerable dose of sunitinib in chemotherapy-naïve pediatric patients is at least 20 mg/m2 on schedule 4/2. The safety profile and PK of sunitinib in pediatric patients with GIST are comparable to those in adults.

• Authors: Arnauld C Verschuur, Viera Bajčiová, Leo Mascarenhas, Reza Khosravan, Xun Lin, Antonella Ingrosso, Katherine A Janeway
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 84 Issue 1 Pg. 41-50 (07 2019) ISSN: 1432-0843 [Electronic] Germany
• PMID: 31006038 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Imatinib Mesylate
• Sunitinib

Topics

• Adolescent
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Female
• Gastrointestinal Neoplasms (drug therapy, pathology)
• Gastrointestinal Stromal Tumors (drug therapy, pathology)
• Humans
• Imatinib Mesylate (administration & dosage)
• Male
• Progression-Free Survival
• Sunitinib (administration & dosage, adverse effects, pharmacokinetics)
• Treatment Outcome