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.

Fig. 1.

Kaplan–Meier plots of survival and EFS after ASCR.

Fig. 2.

Kaplan–Meier plot of EFS after ASCR in patients with M-0 vs M-1+ disease at the time of relapse. There is no statistically significant difference (P = .33).

Fig. 3.

Kaplan–Meier plot of EFS after ASCR in patients whose initial treatment regimen consisted of RT only vs combined RT and chemotherapy. There is no statistically significant difference (P = .27).

Fig. 4.

Kaplan–Meier plot demonstrating a trend toward better EFS after ASCR in patients (n = 5) who received additional RT as a part of their retrieval therapy (P = .07).

Fig. 5.

Kaplan–Meier plot demonstrating a trend toward better EFS after ASCR in patients whose recurrent disease was demonstrated to be sensitive to reinduction chemotherapy (P = .09).