GC-04: PRELIMINARY RESULTS OF A FEASIBILITY PILOT STUDY OF “GEMPOX” (GEMCITABINE, OXALIPLATIN, AND PACLITAXEL) IN PEDIATRIC AND ADULT PATIENTS WITH REFRACTORY OR RECURRENT CENTRAL NERVOUS SYSTEM (CNS) GERM CELL TUMORS (GCT): THE INTERNATIONAL CNS GCT CONSORTIUM TRIAL, CNS GCT- 4

PURPOSE: We present updated findings on the response rate, toxicity and early outcomes of a re-induction regimen of gemcitabine, oxaliplatin and paclitaxel (GemPOx) administered prior to myeloablative chemotherapy and autologous hematopoietic cell rescue (HDCx + AuHCR) in patients with recurrent/refractory central nervous system (CNS) germ cell tumors (GCT). METHODS: Since December 2004, 14 patients (12 mixed malignant (MM) GCT, 2 germinoma; 12 males; mean age 16.5 years, range 7-34 years) have been treated with up to 4 cycles of gemcitabine (800 mg/m2), oxaliplatin (100 mg/m2) and paclitaxel (170 mg/m2), administered on one day at 14 days intervals. Quantitation of cerebrospinal fluid (CSF) GCT-specific exosomal microRNAs to assess response during therapy has recently been incorporated into the protocol. RESULTS: Of 14 patients, five were treated on a preceding feasibility pilot with 1-3 cycles of GemPOx, and nine have been enrolled on an ongoing prospective multi-center trial. Seven patients achieved complete remissions (tumor marker and/or imaging studies), five achieved partial remissions and two developed progressive disease (PD) while on GemPOx; one patient with PD after 1 cycle had pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma; the second patient, with pure pineal choriocarcinoma, progressed following the second cycle of GemPOx. Twelve of the 14 patents subsequently underwent HDCx + AuHCR (2 with tandem transplants). Six of these subsequently received irradiation. Transient hepatotoxicity and pancytopenia were the most commonly observed toxicities. Five patients continue alive and disease-free for 8 + , 19 + , 21 + , 25+ and 27+ months since discontinuation of all therapy. CONCLUSIONS: GemPOx appears to be an effective re-induction regimen for patients with recurrent CNS MMGCT, with acceptable toxicities. The ongoing multi-center, international trial should confirm this and demonstrate the potential for assay of serial CSF GCT-specific exosomal microRNAs in predicting response and durable relapse-free survival with this therapy.