Phase I evaluation of radiation combined with recombinant interferon alpha-2a and BCNU for patients with high-grade glioma.

Abstract

PURPOSE:

A Phase I study to determine the safety, toxicity, and maximum tolerated dose (MTD) of carmustine (BCNU) and interferon alpha-2a (IFN-a) when combined with radiation as initial therapy in high-grade glioma.

METHODS AND MATERIALS:

Patients with newly diagnosed Grade 3 or 4 astrocytoma, oligoastrocytoma, or gliosarcoma were enrolled after surgery. All received radiation therapy to the brain (64.8 Gy/36 fractions), combined with a single dose of BCNU (200 mg/m2) at the start of radiation. Chemotherapy after completing radiation consisted of BCNU 150 mg/m2 once every 7 weeks, and IFN-a 12 x 10(6) units/m2 subcutaneously Days 1-3 each week of a 7-week cycle. Subsequent dose modification was based on constitutional symptoms for IFN-a and on myelosuppression for BCNU.

RESULTS:

Fifteen patients were entered on the study. Four were excluded because they did not receive IFN-a (3 refused treatment and 1 patient left the study due to multiple medical problems). Eleven were evaluable for toxicity and efficacy. Nonhematological toxicity, mainly lethargy and flu-like symptoms, were dose-limiting for IFN-a. After the first 6 patients were treated per the initial protocol, the frequency of IFN-a administration was decreased to Days 1-3 on weeks 1, 3, and 5 of the 7-week cycle for 5 additional patients. Lethargy, fever, chills, myalgias, alopecia, and anorexia occurred in all patients. Other toxicities included nausea and vomiting (91%), central-nervous-system depression or mood changes (64%), headaches (55%), and elevation of liver enzymes (36%). Grade 3-4 leukopenia occurred in 4 (45%) of 11 patients, and Grade 3-4 thrombocytopenia in 3 (27%) of 11 patients. Due to myelosuppressive effects, BCNU dose was not escalated. Median survival of the cohort was 44 months. Objective responses occurred in 5 (56%) of 9 patients and median duration of response was 33 months. The MTD of this combination after radiation therapy is IFN-a 12 x 10(6) units/m2 Days 1-3, on Weeks 1, 3, and 5 of a 7-week cycle and BCNU 150 mg/m2 Day 1, every 7 weeks.

CONCLUSIONS:

Treatment with radiation, IFN-a, and BCNU is feasible and effective in patients with high-grade gliomas, although constitutional symptoms from IFN-a are substantial.

• Authors: S V Rajkumar, J C Buckner, P J Schomberg, T L Cascino, P A Burch, R P Dinapoli
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 40 Issue 2 Pg. 297-302 (Jan 15 1998) ISSN: 0360-3016 [Print] United States
• PMID: 9457812 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Carmustine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Brain Neoplasms (drug therapy, pathology, radiotherapy)
• Carmustine (administration & dosage, adverse effects)
• Combined Modality Therapy
• Female
• Glioma (drug therapy, pathology, radiotherapy)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, adverse effects)
• Male
• Middle Aged
• Radiotherapy (adverse effects)
• Recombinant Proteins
• Survival Analysis