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

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.