Influence of UGT1A1 *6/*28 Polymorphisms on Irinotecan-Related Toxicity and Survival in Pediatric Patients with Relapsed/Refractory Solid Tumors Treated with the VIT Regimen.

OBJECTIVE

The association between UGT1A1*6/28 polymorphisms and treatment outcomes of irinotecan in children remains unknown. This retrospective study investigated the influence of UGT1A16/*28 polymorphisms on irinotecan toxicity and survival of pediatric patients with relapsed/refractory solid tumors.

METHODS

The present study enrolled a total of 44 patients aged younger than 18 years at Sun Yat-sen University Cancer Center between 2014 and 2017.

RESULTS

There were 26 boys and 18 girls; the median age at first VIT course was six years (range: 1-18 years). The tumor types included neuroblastoma (n = 25), rhabdomyosarcoma (n = 11), Wilm's tumor (n = 4), medulloblastoma (n = 2), and desmoplastic small round cell tumor (n = 2). Overall, 203 courses of VIT regimens were prescribed. Neither UGT1A16 nor 28 polymorphisms were associated with the incidence rates of severe (grade III-IV) irinotecan-related toxicities, but tended to reduce the patient overall survival (UGT1A16, = 0.146; UGT1A128, = 0.195). Moreover, patients with mutant UGT1A16 genotypes were more likely to develop grade I-IV irinotecan-related diarrhea ( = 0.043) and anemia ( = 0.002). Overall, the UGT1A128 polymorphism may play a protective role against irinotecan-related diarrhea and abdominal pain.

CONCLUSION

In relapsed/refractory pediatric solid tumors, the UGT1A16 polymorphism was a risk factor of irinotecan-related diarrhea and anemia. The UGT1A128 polymorphism may serve a protective role in irinotecan-related abdominal pain and diarrhea. Both mutations had a tendency to be risk factors for survival. Nevertheless, prospective studies are required to verify such conclusions.