Intratumor RAIT May Improve Survival in Malignant Glioma

PRINCETON, NJ--Direct intratumor radioimmunotherapy (RAIT), withmultiple courses delivered via indwelling or removable catheters,resulted in prolonged survival in patients with malignant glioma.Observations in newly diagnosed patients suggests that this treatmentmay have its greatest benefits as an adjuvant to primary surgicalexcision, Dr. Agostino Arista said at the Fifth Conference onRadioimmunodetection and Radioimmunotherapy of Cancer.

Patients with recurrent malignant glioma had improved survivalwith the treatment, and those with minimal residual disease followingconventional primary therapy showed improved response rates. Thetreatment was associated with no significant local or systemicside effects, said Dr. Arista, of M. Buffalini Hospital, Cesena,Italy, who presented the report for principal investigator P.Riva.

The investigators used two different iodine 131-labeled murinemonoclonal antibodies, BC-2 and BC-4, which react with tenascin,an extracellular antigen associated exclusively with malignantgliomas, Dr. Arista said.

Treatment was carried out in 38 patients after surgery for recurrentglioma and in 14 patients following surgery and other conventionaltreatments for newly diagnosed brain tumors. 131I was deliveredat doses escalating from 5 up to 69 mCi per cycle, and patientsreceived up to six treatments.

Of 48 evaluable patients, 12 experienced complete remissions.Six patients had a partial remission, while nine had stable diseaseand 21 progressed. The study did not include a randomized controlgroup, but median survival in the treated patients was considerablylonger than that reported for comparable patients who receivedconventional therapy (18 months versus 12 months), Dr. Aristasaid.

The likelihood of a response was determined primarily by tumorsize, Dr. Arista continued. The response rate was about 40% inthe group as a whole, 54% in those with small or minimal lesionsfollowing other therapy, and only 23% in those with bulky lesions.Patients with newly diagnosed tumors had a somewhat greater rateof response than those with recurrent disease.

Headaches, the only clinically apparent treatment side effect,occurred in 13 patients and were transient in all cases. Therewas no systemic, hematologic, hepatic, or renal toxicity.

Almost half of the patients developed HAMA (human antimouse antibody)reactions, and the reactions were universal in those who had receivedfour or more treatments. However, these antibodies did not causeallergic reactions to subsequent cycles of therapy.

Improved Irradiation

The treatment protocol resulted in improved irradiation of tumortissue, compared with that achieved with conventional radiotherapy.Target tissue received an estimated average of 350 Gy per treatmentcycle, and dosage exceeded 1,500 Gy in patients who received fouror more treatments.

This improvement stemmed from both a high concentration of themonoclonal antibody in tumor tissue and a long residence time,with a half-life greater than 50 hours, Dr. Arista said.