Phase II study of high‐dose chemotherapy before radiation in children with newly diagnosed high‐grade astrocytoma

Abstract

BACKGROUND High‐grade astrocytomas (HGA) carry a dismal prognosis and compose nearly 20% of all childhood brain tumors. The role of high‐dose chemotherapy (HDCT) in the treatment of HGA remains unclear. METHODS In a nationwide study, The Children's Cancer Group (CCG) prospectively evaluated 102 children with HGA and postoperative residual disease for efficacy and toxicity of four courses of HDCT before radiotherapy (RT). Patients were randomly assigned to one of three couplets of drugs: carboplatin/etoposide (Regimen A), ifosfamide/etoposide (Regimen B), or cyclophosphamide/etoposide (Regimen C). After HDCT, all patients were to receive local RT followed by lomustine and vincristine. Twenty‐six patients were excluded after central neuroradiographic review (n = 8) or pathology review (n = 18). RESULTS Of 76 evaluable patients (median age, 11.95 yrs; range, 3–20 yrs), 30 patients relapsed during HDCT, and 11 others did not complete HDCT because of toxicity. Nonhematologic serious toxicities were common (29%), and 21% of patients did not receive RT. Objective response rates were not associated with amount of residual disease and did not statistically differ between regimens: 27% (Regimen A), 8% (Regimen B), and 29% (Regimen C). Overall survival (OS) was 24% ± 5% at 5 years and did not differ between groups. Median time to an event was longest for Regimen A (283 days compared with 83 and 91 days for Regimens B and C, respectively). The five‐year, event‐free survival (EFS) rate for all patients was 8% ± 3% and 14% ± 7% for Regimen A (P = 0.07). CONCLUSIONS OS and EFS were not affected by histologic grade. Patients who responded to HDCT had a nominally higher survival rate (P = 0.03 for trend). The authors conclude that these commonly used HDCT regimens provide no additional clinical benefit to conventional treatment in HGA, regardless of the amount of measurable residual tumor. Cancer 2005. © 2005 American Cancer Society.

Pediatric Brain Tumors: Current Treatment Strategies and Future Therapeutic Approaches

“…Unfortunately, none of the three treatment arms showed beneficial effect toward survival. 90 The SFOP treated high-grade glioma patients with limited success with a combination of carmustine, cisplatin, and etoposide after surgery. The 5-and 10-year OS were reported at 16% (Ϯ 9%) and 13.3% (Ϯ 9.4%), respectively.…”

In vitro apoptotic induction of human glioblastoma cells by Fas ligand plus etoposide and in vivo antitumour activity of combined drugs in xenografted nude rats

“…However toxic adverse effects are frequently reported (18). Central nervous system-directed treatment using intraventricular drug injection is one approach to overcoming the blood-brain barrier protective effect against anticancer chemotherapy.…”

A phase I trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood

“…2 Although subsequent studies have all utilized chemotherapy, further improvements in outcome have not been realized. [10][11][12][13] With the advent of temozolomide, there was renewed hope that outcome could be improved. The benefit of temozolomide for adults with newly diagnosed HGGs was established in a randomized study by Stupp et al,4 who showed a significant improvement in OS and PFS in newly diagnosed adults with glioblastomas treated with temozolomide during and after RT compared to those treated with RT alone.…”

“…12,13,18 The Children's Cancer Group 9933 (CCG-9933) study evaluated the combinations of "high-dose" carboplatin/VP-16, cyclophosphamide/ VP-16, and ifosfamide/VP-16 prior to RT. 11 More than half of the patients either progressed during chemotherapy or did not complete chemotherapy because of toxicity, and 21% of the patients never received RT. In contrast, the combination of lomustine/temozolomide at the MTD was generally well tolerated, and only one patient ment without a change in tumor-specific treatment is becoming increasingly recognized.…”