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To the Editor:
Tosoni et al.1 presented their findings on protracted low-dose temozolomide, at 75 mg/m2/day for 21 days in 28-day cycles. They found over 50% of patients had lymphopenia and more than 25% had at least grade 3 lymphopenia.
Although the rationale for continuous temozolomide and dose-dense temozolomide is to suppress O6-alkylguanine-DNA alkyltransferase (AGAT) activity, the toxicity profile of such regimens is unclear. The various schedules of temozolomide used across different trials also add to the confusion.1–5
However, if the trials were compared based on number of days of temozolomide exposure, dose intensity on a per month basis, and months on temozolomide, then a picture emerges that suggests that lymphopenia from chronic exposure to temozolomide is a function of days exposed to temozolomide, dose intensity, and number of months on temozolomide (table).
Comparing to the standard dosing regimen (regimen 1), regimens 2 and 4 …
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