Temozolomide and intravenous irinotecan for refractory Ewing's sarcoma: A retrospective review.

8526 Background: Preclinical models show sequence-dependent synergy with temozolomide (T) + irinotecan (I), and a pediatric Phase I trial has been reported (Clin Cancer Res; 10: 840-8). Because responses were seen in patients with Ewing's sarcoma (ES), additional patients were treated with these commercially available drugs following study completion.,We reviewed data from all patients with refractory ES treated with combined T + I at 3 institutions, including 7 patients treated on the above Phase I trial.,Fourteen patients (median 18 yrs, range 7-33) have received a total of 74 courses to date (median =5). All received standard 5-drug therapy initially, and 8 had stem cell transplants (6 tandem) for metastatic disease. Four relapsed on initial therapy; others relapsed a median of 7 mos (range 5-13) after completion. All but four received from 1-5 prior treatment regimens, and 8 patients received prior pelvic irradiation. Relapse sites were primary bone (5), lung (8), bone metastases (6), and marrow (2). Patients received oral T 100 mg/m/day on days 1-5 + intravenous I at 10 mg/m/day (10), 15 mg/m/day (3), or 20 mg/m/day (1) on days 1-5 and 8-12. Subsequent courses were planned every 21 days (7) or 28 days (7). Grade 3-4 diarrhea or vomiting was seen in 14% of courses. Excluding the 2 patients with marrow disease, grade 3-4 neutropenia or thrombocytopenia occurred in 9 (14%) of 66 courses; 2 patients received G-CSF. One complete, 2 partial, and 3 minor responses (31%, 44%, and 46% reduction in tumor volume) were seen in 12 evaluable patients. Additionally, 2 patients without measurable disease were progression-free for 6 and 13 months before electively stopping therapy. Two more patients continue on therapy past course 6 with stable or responding disease. Nine patients (64%) had substantial symptomatic relief with the first course of treatment, irrespective of ultimate response. Over 80% of I doses were administered at home.,T + I is tolerable in heavily pretreated patients, and shows activity in highly refractory ES. Home administration was safe and is reasonable for palliative care. A formal Phase II study using uniform doses and schedules will better define activity. No significant financial relationships to disclose.