CHEMOTHERAPY FOR PATIENTS WITH RECURRENT OR REFRACTORY NEUROBLASTOMA - A POG PHASE-II STUDY

Purpose: The purpose of this study was to evaluate the efficacy and to xicity of three different salvage regimens (Rx) in children with recur rent or refractory neuroblastoma. Patients and Methods: Forty-six chil dren with recurrent or refractory neuroblastoma received treatment acc ording to one of three regimens: Rx 1 (five patients), high-dose cispl atin (HDP) (200 mg/m(2)) with concurrent sodium thiosulfate (STS) (9.9 g/m(2)) as a nephroprotectant and etoposide (VP-16) (200 mg/m(2)/day for 3 days); Rx 2 (22 patients), high-dose carboplatin (HD-CBDCA) (500 mg/m(2)/day for 2 days) and VP-16 (100 mg/m(2)/day for 3 days); Rx 3 (19 patients), ifosfamide (1.5 g/m(2)/day for 3 days) followed by CBDC A (400 mg/m(2)) on day 4. Chemotherapy was administered every 3-4 week s. Responses were assessed following four courses with or without surg ery. Patients achieving less than a partial response (PR) on their pri mary treatment were crossed over to the next regimen (i.e., Rx 1 --> R x 2 <----> Rx 3). Results: Rx 1 was ended early owing to grade 4 nephr otoxicity in two patients following their first course. Ten of 22 eval uated patients (45%) primarily (n = 19) or secondarily (n = 3) treated by Rx 2 responded [five complete response (CR) and five PRs]. Nine of the 23 evaluated patients (39%) on Rx 3 as primary (n = 18) or second ary (n = 5) treatment responded (one CR and eight PRs). Grades 3-4 neu tropenia and thrombocytopenia occurred after 80% and 50% of courses ad ministered on Rx 2 and Rx 3, respectively. Central venous line infecti ons were the most commonly documented infections on these regimens. Co nclusions: Rx 2 and Rx 3 are active combinations in patients with recu rrent or refractory neuroblastoma and are associated with manageable t oxicity. HDP administered as a short i.v. infusion with concurrent STS infusion cannot be safely given to children with neuroblastoma pretre ated with cisplatin.