Thiotepa/topotecan/carboplatin with autologous stem cell rescue in recurrent/refractory/poor prognosis pediatric malignancies of the central nervous system.

Abstract

BACKGROUND:

Thiotepa and carboplatin are known to be active in central nervous system tumors. Topotecan potentiates the anti-cancer effects of alkylators and crosses the blood-brain barrier. We present ten patients with recurrent or progressive central nervous system malignancies treated on a myeloablative regimen using these drugs.

METHODS:

Treatment included: Thiotepa 300 mg/m(2) on days -8, -7, and -6; topotecan 2 mg/m(2) on days -8, -7, -6, -5, and -4; and carboplatin approximately 500 mg/m(2) (Calvert formula-area under the curve = 7) on days -5, -4, and -3. Stem cell rescue was on day 0.

RESULTS:

Age at study entry ranged from 2.5 to 20 years old (median age 8.7 years). Five had medulloblastoma (MB), four had high grade glioma (HGG), and one had trilateral retinoblastoma/pineoblastoma (tRB/PB). Prior treatment for all patients included surgery and chemotherapy (1-7 regimens, median 2). Nine patients received radiotherapy; one patient did not receive radiotherapy pre-study. Three patients had residual disease at the time of transplant. There were two toxic deaths. Four patients are event-free survivors at a median of 6 years (range 2.8-7.6 years) after treatment including 2/5 MB patients, 1/4 HGG patients, and the tRB/PB patient. Four of the seven patients with no evidence of disease/minimal residual disease status at the time of stem cell rescue are long-term survivors versus 1/3 with measurable disease.

CONCLUSION:

Thiotepa/topotecan/carboplatin may help consolidate remission of poor prognosis pediatric central nervous system tumors. Diagnosis and extent of disease prior to stem cell rescue may have an impact on outcome.

• Authors: Stephen W Gilheeney, Yasmin Khakoo, Mark Souweidane, Suzanne Wolden, Farid Boulad, Ira J Dunkel
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 54 Issue 4 Pg. 591-5 (Apr 2010) ISSN: 1545-5017 [Electronic] United States
• PMID: 19998470 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Topotecan
• Thiotepa
• Carboplatin

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Central Nervous System Neoplasms (drug therapy)
• Child
• Child, Preschool
• Combined Modality Therapy
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Male
• Neoplasm Recurrence, Local (drug therapy)
• Prognosis
• Thiotepa (administration & dosage, adverse effects)
• Topotecan (administration & dosage, adverse effects)
• Young Adult