title: High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma.
abstract: Recurrent medulloblastoma is highly lethal in previously irradiated patients. Previously irradiated patients with M-0-M-3 recurrences who achieved a minimal disease state prior to protocol enrollment received carboplatin (Calvert formula with area under the curve = 7 mg/mL min, maximum 500 mg/m(2)/day) on days -8 to -6, and thiotepa (300 mg/m(2)/day) and etoposide (250 mg/m(2)/day) on days -5 to -3, followed by autologous stem cell rescue (ASCR) on day 0. Twenty-five patients, aged 7.6-44.7 years (median 13.8 years) at ASCR, were treated. Three (12%) died of treatment-related toxicities within 30 days of ASCR, due to multiorgan system failure (n = 2) and aspergillus infection with veno-occlusive disease (n = 1). Tumor recurred in 16 at a median of 8.5 months (range 2.3-58.5 months). Six are event-free survivors at a median of 151.2 months post-ASCR (range 127.2-201.6 months). The Kaplan-Meier estimate of median overall survival is 26.8 months (95% CI: 11.9-51.1 months) and of event-free survival (EFS) and overall survival are both 24% (95% CI: 9.8%-41.7%) at 10 years post-ASCR. M-0 (vs M-1 + ) recurrence prior to protocol, lack of tissue confirmation of relapse, and initial therapy of radiation therapy (RT) alone (vs RT + chemotherapy) were not significantly associated with better EFS (P = .33, .34, and .27, respectively). Trends toward better EFS were noted in patients (n = 5) who received additional RT as part of their retrieval therapy (P = .07) and whose recurrent disease was demonstrated to be sensitive to reinduction chemotherapy (P = .09). This retrieval strategy provides long-term EFS for some patients with previously irradiated recurrent medulloblastoma. The use of additional RT may be associated with better outcome.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Box 185, 1275 York Avenue, New York, NY 10065, USA. dunkeli@mskcc.org
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Dunkel
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Gardner
authors.forename: James H
authors.initials: JH
authors.lastname: Garvin
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.forename: Weiji
authors.initials: W
authors.lastname: Shi
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Finlay
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002528:Cerebellar Neoplasms / Q000401:mortality / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008527:Medulloblastoma / Q000401:mortality / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000628:therapy*; D011788:Quality of Life; D011878:Radiotherapy; D016879:Salvage Therapy / Q000379:methods*; D013852:Thiotepa / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D005047:Etoposide; D013852:Thiotepa; D016190:Carboplatin