Treatment > Gemcitabine · Temozolomide Clinical Trials

Meeting Abstract

Phase I study of temozolomide in conjunction with gemcitabine

Rakesh Goel, Stanley Gertler, David J Stewart, Scott Laurie, Glenwood Goss, Neil Reaume, Joanne Roach, Deborah Bedard, Angela Rodgers, David Cutler

Ottawa Regional Cancer Centre, Ottawa, ON, Canada; Schering Canada Inc, Pointe Claire, PQ, Canada; Schering-Plough Research Institute, Kenilworth, NJ

Temozolomide (TZ) is an oral alkylating agent used in the treatment of brain tumors, and malignant melanoma. 
Gemcitabine (GC) is a nucleoside analog active versus several human tumors. 
In vitro, these 2 drugs exhibit additive cytotoxic effects against the astrocytoma U373MG cell line. 
A phase I clinical study using these 2 drugs in combination was initiated. 
Cohort 1 received: TZ 100 mg/m²/d, days 1-7 and 15-21; GC 750 mg/m^{2 days} 1, 8, and 15; every 28 days. 
Cohort 2 received TZ 125 mg/m² and GC 750 mg/m². 
Cohort 3 received TZ 125 mg/m² and GC 1000 mg/m². 
Further dose escalation will take place. 
Patient characteristics: male 6/female 6; median age 53 (range 26-74); performance status 0 (n=0), 1 (n=8), and 2 (n=4); prior therapy: chemotherapy 9, radiotherapy 6, no therapy 1; tumor types: non-small cell lung 4, renal cell 2, primary brain tumor 2, unknown primary 1, colon 1, salivary gland 1, adrenal cortical 1. 
To date, 6 patients were treated on cohort 1, 4 on cohort 2, and 2 on cohort 3. 
At least 1 more patient will be treated on cohort 3. 
The regimen is well tolerated. 
Of the 9 patients off study, the number of cycles given: 1 (n=2), 2 (n=3), 3 (n=2), 4 (n=1), 5 (n=1). 
One patient remains on cohort 2 (1 cycle given), and 2 remain on cohort 3 (both received 1 cycle). 
The nadir counts (x 10⁹/L) after cycle 1: cohort 1 wbc 3.2 (range 1.6-4.4), PMN 1.9 (range 1.0-2.5), platelets 104 (range 53-211), cohort 2 wbc 3.3 (range 2.2-4.2), PMN 1.3 (0.8-1.8), platelets 130 (17-173). 
No grade 3 or 4 non-hematologic toxicity has been observed. 
Encouraging activity of the regimen is suggested in this group of heavily pre-treated patients with resistant tumors; 4 patients received more than 2 courses of therapy (1 patient each with primary brain tumor, renal cell ca, colon ca, and non-small cell lung ca). 
The study is ongoing. 

Supported by Schering-Plough Research Institute.

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