Regimen-Related Toxicity of Myeloablative Chemotherapy With BCNU, Thiotepa, and Etoposide Followed by Autologous Stem Cell Rescue for Children With Newly Diagnosed Glioblastoma Multiforme: Report From the Children’s Cancer Group

Regimen-Related Toxicity of Myeloablative Chemotherapy With BCNU, Thiotepa, and Etoposide Followed by Autologous Stem Cell Rescue for Children With Newly Diagnosed Glioblastoma Multiforme: Report From the Children’s Cancer Group

Regimen-Related Toxicity of Myeloablative Chemotherapy With BCNU, Thiotepa, and Etoposide Followed by Autologous Stem Cell Rescue for Children With Newly Diagnosed Glioblastoma Multiforme: Report From the Children’s Cancer Group

Abstract

BACKGROUND:

The survival of children with glioblastoma multiforme (GBM) remains poor. In an effort to improve the cure rate of children with this disease, high-dose chemotherapy followed by autologous stem cell rescue (ASCR) has been evaluated. We report the regimen-related toxicity (RRT) and survival seen in 11 children with newly diagnosed GBM treated with high-dose chemotherapy on a Children’s Cancer Group study (CCG-9922).

PROCEDURES:

This phase II pilot study, intended to treat 30 patients, accrued 11 patients from July, 1993, to April, 1995. The pre-ASCR preparative regimen included BCNU 100 mg/m2 every 12 hr for a total of six doses on days -8, -7, -6; thiotepa 300 mg/m2/day on days -5, -4, -3; and etoposide250 mg/m2/day on days -5, -4, -3. All patients received delayed radiotherapy at a dose of 5,400 cGy to the primary site commencing on approximately day +42 after ASCR.

RESULTS:

Five patients (45%) developed significant, nonfatal (grade III or IV) pulmonary and/or neurological toxicities. Three patients developed signs and/or symptoms of idiopathic interstitial pneumonitis. Eight patients (73%) have died, two (18%) of toxicity, and six (55%) of disease progression. Three patients (27%) achieved and remain in complete radiographic remission 2.9, 3.9, and 5.1 years from ASCR. One of these three, developed a lymphoblastic non-Hodgkins lymphoma (NHL) 3. 5 years post-ASCR. The survival rates for these 11 children at 1 year and 2 years are 73% +/- 13% and 46% +/- 14%, respectively. The progression-free survival rates at 1 year and at 2 years are 64% +/- 14% and 46% +/- 14%, respectively.

CONCLUSIONS:

We conclude that high-dose chemotherapeutic regimens followed by ASCR is a feasible treatment of childhood GBM. The BCNU-based preparative regimen utilized in this study was associated with prohibitive pulmonary toxicity.

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