Chloroquine as Adjuvant to the Treatment of Glioblastoma Multiforme, A Randomized Trial

ANTECEDENTS: We have shown experimentally a significant adjuvant effect of quinacrine (an analog of chloroquine) on cultured malignant glial cells and C6 implanted malignant glioma in Wistar rats. When quinacrine was added to the standard therapy with carmustine cell destruction and tumor diminution were higher than therapy with carmustine alone. Those results were published in Neurosurgery 2001; 49:969-973 (at that time the manuscript was "in press").

The present protocol started with a controlled, open-label clinical trial on 7 patients with GBM and 7 contemporary control patients. All patients received the same treatment of extensive surgery, carmustine therapy and irradiation at the standard doses as (as described in our previous report Surgical Neurology 2000; 53:157-162). Once selected to enter the study the patients were allocated alternatively in the chloroquine or the control group. Endpoint evaluation was settled as surviving time after the beginning of therapy and the end point follow-up was settled in survivors at two years after the beginning of treatment.

18 months after the beginning of the open trial it was observed that chloroquine treated patients had a longer survival and no adverse effects to chloroquine therapy were seen.

At that time it was decided to start the second part of the protocol designed as a double-blind placebo-controlled trial, ideal number of patients to be included was settled in 15 patients on each group.

The results of the 1st. phase of the study by the open-label trial were published in Neurosurgical Focus (http://www.aans.org/education/journal/neurosurgical/feb03/14-2-3.pdf) on February, 2003.