Chloroquine and Hydroxychloroquine

Property	Information
Drug Name	Chloroquine and Hydroxychloroquine
FDA Approval	Not specified
Used for	Not specified
Clinical Trial Phase	Not specified
Clinical Trial Explanation	Not specified
Common Side Effects	Not specified
OS without	Not specified
OS with	Not specified
PFS without	Not specified
PFS with	Not specified
Usefulness Rating	Not rated
Usefulness Explanation	Not specified
Toxicity Level	Not specified
Toxicity Explanation	Not specified

From Ben Williams Book: 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.Property "Has original text" (as page type) with input value "In aseries of studies conducted in Mexico City (23, 24, 25) patients received the</br>traditional chemotherapy agent BCNU, with or without a 150 mg daily dose of</br>chloroquine (the equivalent of 250 mg chloroquine phosphate). The results were that</br>patients receiving chloroquine had a median survival time of 25-33 months, while those</br>receiving BCNU alone had a median survival time of 11 months. Chloroquine at the dose</br>used had no detectable toxicity. Because the cytotoxic mechanism of BCNU is similar to</br>that of Temodar, it seems likely that chloroquine should increase the efficacy of Temodar,</br>although this has yet to be demonstrated. One of several mechanisms by which</br>chloroquine makes chemotherapy more effective is that it inhibits autophagy, an</br>intracellular process that involves the cell digesting some of its internal parts to allow</br>repair of the damage caused by the chemotherapy.</br></br>Disappointingly, a multi-center phase I\/II trial testing the addition</br>of7hydroxychloroquine (which differs from chloroquine only by a single hydroxyl group)</br>to standard radiochemotherapy for newly diagnosed glioblastoma failed to show any</br>improvement in survival over historical averages. In the phase I safety and toxicity study,</br>all 3 subjects given 800 mg\/d hydroxychloroquine along with chemoradiation</br>experienced grade 3 or 4 neutropenia or thrombocytopenia, and 600 mg\/d was</br>determined to be the maximum tolerated dose. 76 patients were then treated at this dose</br>in the phase 2 cohort. Autophagy inhibition (the proposed mechanism of action) was not</br>consistently achieved at that dose, and patient survival (median OS 15.6 months, 2-year</br>survival of 25%) was not improved relative to historical control groups. The study</br>concluded that hydroxychloroquine was ineffective in this context at the maximum</br>tolerated dose (304).</br></br></br>Recent preclinical work (305) has shown increased reliance on autophagy and sensitivity</br></br>to chloroquine treatment in EGFR-overexpressing glioma cells, and any future trials with</br>chloroquine for high-grade gliomas may benefit from a subgroup analysis based on EGFR</br>status.</br>traditional chemotherapy agent BCNU, with or without a 150 mg daily dose of</br>chloroquine (the equivalent of 250 mg chloroquine phosphate). The results were that</br>patients receiving chloroquine had a median survival time of 25-33 months, while those</br>receiving BCNU alone had a median survival time of 11 months. Chloroquine at the dose</br>used had no detectable toxicity. Because the cytotoxic mechanism of BCNU is similar to</br>that of Temodar, it seems likely that chloroquine should increase the efficacy of Temodar,</br>although this has yet to be demonstrated. One of several mechanisms by which</br>chloroquine makes chemotherapy more effective is that it inhibits autophagy, an</br>intracellular process that involves the cell digesting some of its internal parts to allow</br>repair of the damage caused by the chemotherapy.</br></br>Disappointingly, a multi-center phase I\/II trial testing the addition</br>of7hydroxychloroquine (which differs from chloroquine only by a single hydroxyl group)</br>to standard radiochemotherapy for newly diagnosed glioblastoma failed to show any</br>improvement in survival over historical averages. In the phase I safety and toxicity study,</br>all 3 subjects given 800 mg\/d hydroxychloroquine along with chemoradiation</br>experienced grade 3 or 4 neutropenia or thrombocytopenia, and 600 mg\/d was</br>determined to be the maximum tolerated dose. 76 patients were then treated at this dose</br>in the phase 2 cohort. Autophagy inhibition (the proposed mechanism of action) was not</br>consistently achieved at that dose, and patient survival (median OS 15.6 months, 2-year</br>survival of 25%) was not improved relative to historical control groups. The study</br>concluded that hydroxychloroquine was ineffective in this context at the maximum</br>tolerated dose (304).</br></br></br>Recent preclinical work (305) has shown increased reliance on autophagy and sensitivity</br></br>to chloroquine treatment in EGFR-overexpressing glioma cells, and any future trials with</br>chloroquine for high-grade gliomas may benefit from a subgroup analysis based on EGFR</br>status." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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