No salvage using high-dose chemotherapy plus/minus reirradiation for relapsing previously irradiated medulloblastoma.

Abstract

PURPOSE:

Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation.

METHODS AND MATERIALS:

In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa (+/- carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible.

RESULTS:

Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months.

CONCLUSIONS:

Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few exceptions. A salvage therapy for medulloblastoma after CSI still needs to be sought.

• Authors: Maura Massimino, Lorenza Gandola, Filippo Spreafico, Veronica Biassoni, Roberto Luksch, Paola Collini, Carlo N Solero, Fabio Simonetti, Emanuele Pignoli, Graziella Cefalo, Geraldina Poggi, Piergiorgio Modena, Luigi Mariani, Paolo Potepan, Marta Podda, Michela Casanova, Emilia Pecori, Stefania Acerno, Andrea Ferrari, Monica Terenziani, Cristina Meazza, Daniela Polastri, Fernando Ravagnani, Franca Fossati-Bellani
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 73 Issue 5 Pg. 1358-63 (Apr 01 2009) ISSN: 1879-355X [Electronic] United States
• PMID: 19019566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Granulocyte Colony-Stimulating Factor
• Vincristine
• Etoposide
• Cyclophosphamide
• Thiotepa
• Carboplatin
• Cisplatin
• Methotrexate

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Cerebellar Neoplasms (drug therapy, mortality, radiotherapy, surgery)
• Child
• Child, Preschool
• Cisplatin (administration & dosage, adverse effects)
• Combined Modality Therapy (methods)
• Cyclophosphamide (administration & dosage, adverse effects)
• Disease-Free Survival
• Drug Administration Schedule
• Etoposide (administration & dosage, adverse effects)
• Female
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Male
• Medulloblastoma (drug therapy, mortality, radiotherapy, surgery)
• Methotrexate (administration & dosage, adverse effects)
• Neoplasm Recurrence, Local (drug therapy, mortality, radiotherapy, surgery)
• Radiotherapy Dosage
• Remission Induction (methods)
• Salvage Therapy
• Thiotepa (administration & dosage, adverse effects)
• Vincristine (administration & dosage, adverse effects)
• Young Adult