Treatment > Temozolomide Clinical Trials

Meeting Abstract

A Phase I Trial of Chronic Oral Fixed Dose Temozolomide

SF Jones, FA Greco, JD Hainsworth, VG Gian, FT Miranda, JF Patton, NT Willcutt, MN Baker, HA Burris III

The Sarah Cannon Cancer Center/Tennessee Oncology, Nashville, TN

Temozolomide is an imidazotetrazine that is spontaneously cleaved in vivo to MTIC. 
Temozolomide is currently approved (orally qd x 5 every 28 days) for the treatment of anaplastic astrocytoma, and has demonstrated activity in a variety of other tumor types. 
Extended dosing (75 mg/m2/d po qd for 6 weeks) has been explored in an attempt to increase dose intensity and antitumor activity. 
This phase I trial was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of temozolomide administered continuously for 5 out of every 7 days. 
The incorporation of 2 days rest each week may allow for increased tolerability and could potentially delay the development of drug resistance. 
To simplify dosing, a "fixed" or flat dose of drug was used, so that all patients received the same dose regardless of their BSA. A cycle was defined as 4 weeks of treatment. 
To date, a total of 37 patients (median age 60 years, range 33–90; 21 males/16 females; median PS 1) have received 87+ (range 1–5+) cycles at 6 dose levels (100, 140, 180, 220, 250, and 300 mg/day). 
Two patients (1 each at 220 and 250 mg/d, respectively) have experienced dose-limiting thrombocytopenia. 
Platelet nadirs (23K and 20K) occurred after 6 weeks of treatment and the duration of grade 3 thrombocytopenia was 10 and 26 days, respectively. 
No platelet transfusions were required. 
No grade 4 thrombocytopenia or neutropenia has been reported. 
Non-hematologic toxicities have been mild to moderate and consist primarily of nausea and vomiting which has been managed with phenothiazines. 
Two partial responses have been reported in patients with melanoma and colon cancer. 
Patient accrual is ongoing with new patients receiving 360 mg/day for 5 days continuously out of every 7 days. 
Increased dose intensity can be achieved with this extended oral schedule.

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