On 2014 Nov 19, Francisco Felix commented:

This report is highly provocative because it poses the question of administration density and dosing for temozolomide. Data from phase I-II trials settles the issue for two basic administration schemes. In the first one, temozolomide is given concomitant with radiotherapy at a dose ranging from 75-90 mg/m2, 5 days a week, for 6 consecutive weeks, with a cumulative total dose of 2250-2700 mg/m2. This protocol is very well tolerated with virtually no grade III-IV toxicities. The second one is a 5-day administration course with a total cumulative dose of 750-1000 mg/m2 per course and 28-day intervals. It is also very well tolerated. The dosing "scheme" inadvertently used with the reported patient can be viewed as a dose-dense version of the first protocol, with a nearly equal cumulative dose (2560 mg/m2) in about half the time span (3 weeks versus the normal 6-week interval). As such, it is probably not really correct to classify it as a >3 times normal dose, but a "regular" dose administered in a dose-dense way. Of course, this is only a way of wording and does not change the facts in no manner. The fact is it should be worthwhile to plan dose-dense phase I trials of temozolomide for pediatric patients, to test the hypothesis of this report: higher peak doses of temozolomide could overcome intrinsic tumor resistance and be more effective?

On 2014 Nov 19, Francisco Felix commented:

This report is highly provocative because it poses the question of administration density and dosing for temozolomide. Data from phase I-II trials settles the issue for two basic administration schemes. In the first one, temozolomide is given concomitant with radiotherapy at a dose ranging from 75-90 mg/m2, 5 days a week, for 6 consecutive weeks, with a cumulative total dose of 2250-2700 mg/m2. This protocol is very well tolerated with virtually no grade III-IV toxicities. The second one is a 5-day administration course with a total cumulative dose of 750-1000 mg/m2 per course and 28-day intervals. It is also very well tolerated. The dosing "scheme" inadvertently used with the reported patient can be viewed as a dose-dense version of the first protocol, with a nearly equal cumulative dose (2560 mg/m2) in about half the time span (3 weeks versus the normal 6-week interval). As such, it is probably not really correct to classify it as a >3 times normal dose, but a "regular" dose administered in a dose-dense way. Of course, this is only a way of wording and does not change the facts in no manner. The fact is it should be worthwhile to plan dose-dense phase I trials of temozolomide for pediatric patients, to test the hypothesis of this report: higher peak doses of temozolomide could overcome intrinsic tumor resistance and be more effective?