Wednesday 26 August 2015
Should we take chloroquine
I just looked at the new pdf posted by Ben Williams and it states there that addition of it to the standard treatment did not produce any benefit except for tumors with egfr3. So I am quite confused now if we should take it or not since our tumor is tp53 mutated , might have pten loss but no egfr3.
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Anna,
ReplyDeleteI collaborated with Ben for his 2015 update, and it was I that wrote the new material on chloroquine/hydroxychloroquine.
Hydroxychloroquine is very similar to chloroquine, but not identical, so we can't with certainty extrapolate the results of the hydroxychloroquine trial to chloroquine proper.
In an unpublished retrospective study, 28 patients who received chloroquine + radiation + BCNU treatment were separated by EGFRvIII status. These patients were also compared with a control group not receiving chloroquine. Survival benefit of chloroquine was particularly pronounced for those positive for EGFRvIII (median survival increased from 3 months to 15 months). In this study, those negative for EGFRvIII also seemed to benefit from chloroquine but the benefit was not as dramatic (median survival 10 months versus 5 months).
At least some of these patients were included in the trials done in Mexico (Sotelo et al. recruiting 2000-2004, published 2006). The grouping of the patients by EGFRvIII status was not part of the trial design, and was done retrospectively, meaning that patients in each group (EGFRv3+ chloroquine+, EGFRv3+ chloroquine-, EGFRv3- chloroquine+, EGFRv3- chloroquine-) were not necessarily well-matched for prognostic variables (age, extent of resection, MGMT etc.).
Nonetheless, preclinical work also validates that EGFR-driven tumors may be especially responsive to chloroquine. That doesn't it mean it is without effect for tumors not overexpressing EGFR/EGFRv3, just that it might be somewhat less effective.
The TP53 mutation adds another layer of complexity, as some preclinical evidence also shows that chloroquine might be less effective for tumors with mutant TP53. Mike has also been grappling with this question.
A big question is how well does he tolerate the chloroquine? Any side-effects?
His whit blood cells are lower than normal but that is probably from tmz. Otherwise there is no side effects so far.
DeleteStill it is just slightly below normal. Mine are always at 2300 or less and I"m fine with it. (Effect of chernobyl I think)
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