View source for Chloroquine and Hydroxychloroquine



{{TreatmentInfo
|drug_name=Chloroquine and Hydroxychloroquine
|treatment_category=Repurposed Drugs
|book_text=In aseries of studies conducted in Mexico City (23, 24, 25) patients received the
traditional chemotherapy agent BCNU, with or without a 150 mg daily dose of
chloroquine (the equivalent of 250 mg chloroquine phosphate). The results were that
patients receiving chloroquine had a median survival time of 25-33 months, while those
receiving BCNU alone had a median survival time of 11 months. Chloroquine at the dose
used had no detectable toxicity. Because the cytotoxic mechanism of BCNU is similar to
that of Temodar, it seems likely that chloroquine should increase the efficacy of Temodar,
although this has yet to be demonstrated. One of several mechanisms by which
chloroquine makes chemotherapy more effective is that it inhibits autophagy, an
intracellular process that involves the cell digesting some of its internal parts to allow
repair of the damage caused by the chemotherapy.

Disappointingly, a multi-center phase I\/II trial testing the addition
of7hydroxychloroquine (which differs from chloroquine only by a single hydroxyl group)
to standard radiochemotherapy for newly diagnosed glioblastoma failed to show any
improvement in survival over historical averages. In the phase I safety and toxicity study,
all 3 subjects given 800 mg\/d hydroxychloroquine along with chemoradiation
experienced grade 3 or 4 neutropenia or thrombocytopenia, and 600 mg\/d was
determined to be the maximum tolerated dose. 76 patients were then treated at this dose
in the phase 2 cohort. Autophagy inhibition (the proposed mechanism of action) was not
consistently achieved at that dose, and patient survival (median OS 15.6 months, 2-year
survival of 25%) was not improved relative to historical control groups. The study
concluded that hydroxychloroquine was ineffective in this context at the maximum
tolerated dose (304).


Recent preclinical work (305) has shown increased reliance on autophagy and sensitivity

to chloroquine treatment in EGFR-overexpressing glioma cells, and any future trials with
chloroquine for high-grade gliomas may benefit from a subgroup analysis based on EGFR
status.
traditional chemotherapy agent BCNU, with or without a 150 mg daily dose of
chloroquine (the equivalent of 250 mg chloroquine phosphate). The results were that
patients receiving chloroquine had a median survival time of 25-33 months, while those
receiving BCNU alone had a median survival time of 11 months. Chloroquine at the dose
used had no detectable toxicity. Because the cytotoxic mechanism of BCNU is similar to
that of Temodar, it seems likely that chloroquine should increase the efficacy of Temodar,
although this has yet to be demonstrated. One of several mechanisms by which
chloroquine makes chemotherapy more effective is that it inhibits autophagy, an
intracellular process that involves the cell digesting some of its internal parts to allow
repair of the damage caused by the chemotherapy.

Disappointingly, a multi-center phase I\/II trial testing the addition
of7hydroxychloroquine (which differs from chloroquine only by a single hydroxyl group)
to standard radiochemotherapy for newly diagnosed glioblastoma failed to show any
improvement in survival over historical averages. In the phase I safety and toxicity study,
all 3 subjects given 800 mg\/d hydroxychloroquine along with chemoradiation
experienced grade 3 or 4 neutropenia or thrombocytopenia, and 600 mg\/d was
determined to be the maximum tolerated dose. 76 patients were then treated at this dose
in the phase 2 cohort. Autophagy inhibition (the proposed mechanism of action) was not
consistently achieved at that dose, and patient survival (median OS 15.6 months, 2-year
survival of 25%) was not improved relative to historical control groups. The study
concluded that hydroxychloroquine was ineffective in this context at the maximum
tolerated dose (304).


Recent preclinical work (305) has shown increased reliance on autophagy and sensitivity

to chloroquine treatment in EGFR-overexpressing glioma cells, and any future trials with
chloroquine for high-grade gliomas may benefit from a subgroup analysis based on EGFR
status.
}}