Abstract
9546 Background: Platinum analogues in combination with topoisomerase 1 inhibitors have been shown in in vitro studies to have synergistic anti-tumor activity. This study estimated the maximum tolerated dose (MTD) of OXA in combination with a protracted schedule of IRN in children with refractory solid tumors. Methods: OXA was administered over 2 hrs on days 1 and 8 in combination with IRN iv over 1 hr on days 1–5 and 8–12 of a 21-day cycle. An oral cephalosporin was administered daily to ameliorate IRN-associated diarrhea. Pharmacokinetic studies of OXA and UGT1A1 genotyping were performed during course 1 in consenting patients. Results: 13 patients (median age 16 yrs, 4 M) were enrolled. Dose-limiting diarrhea (n=3), serum lipase elevation (n=3), serum amylase elevation (n=2), colitis (n=1), abdominal pain (n=1) and headache (n=1) occurred at the 1st dose level (60 mg/m2/dose OXA; 20 mg/m2/dose of IRN) in the first 3 patients. Only 1/7 patients treated with reduced doses of both agents (40 mg/m2/dose OXA; 15 mg/m2/dose IRN) experienced DLT, diarrhea. When the OXA dose (60 mg/m2) was increased with the reduced IRN dose (15 mg/m2) 2/3 patients had DLT (1 diarrhea, 1 hypokalemia). Myelosuppression was minimal at all dose levels. One patient with alveolar rhabdomyosarcoma previously treated with irinotecan (dose level 2: 40 mg/m2/dose OXA; 15 mg/m2/dose IRN) had an unconfirmed complete response of her breast metastases and one patient with refractory neuroblastoma had disease stabilization through 6 courses of therapy. The frequency of 6/6, 6/7, and 7/7 UGT1A1 promoter genotypes were 5/10, 4/10, and 1/10, respectively. Conclusions: The MTD using this schedule with oral cephalosporin support was oxaliplatin 40 mg/m2/dose with irinotecan 15 mg/m2/dose. There was some evidence of benefit but significant toxicity, both expected (diarrhea) and unexpected (elevation in pancreatic enzymes), was also observed. [Table: see text]
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
