Treatment > Irinotecan

Meeting Abstract

A Phase II Trial of Irinotecan (CPT-11) in Recurrent Glioma

J Buckner, J Reid, L Schaaf, S Cha, K Wright, R Marks, M Wiesenfeld, A Hatfield, J Krook, S Nair, P Schaefer, L Miller

This trial evaluated the efficacy and toxicity of CPT-11 given IV to pts with recurrent glioma and the PK of CPT-11, SN-38, SN-38 glucuronide, and APC in these pts. 
Pts with tumor growth on MRI scan > 8 wks after end of radiation therapy and stable corticosteroid doses > 2 wks prior to baseline scan received CPT-11 125 mg/m2 (100 mg/m2 if prior nitrosourea) wkly for 4 wks followed by a 2-week rest (Arm A), or 300 mg/m2 (250 mg/m2 if prior nitrosourea) every 3 wks (Arm B). 
In total, 64 eligible pts entered the trial, 32 on each arm. 
Median age was 56 years (range 25-74), 79% had on-study ECOG PS = 0-1, and 50 pts had received prior nitrosourea-based chemotherapy. 
In pts completing treatment, 2/31 in arm A and 2/28 in arm B demonstrated tumor regression. 
Five other pts remain on treatment and are stable. 
Toxicity in Arm A consisted primarily of grade 2 leukopenia and diarrhea, although 1 patient experienced grade 4 infection at the starting dose. 
Toxicity in Arm B included 4 pts with grade 4 diarrhea and 1 pt with grade 5 neutropenic sepsis. 
Dose escalation occurred in 4 Arm-A and 17 Arm-B pts; only 2 Arm-A and 1 Arm-B pts required dose reductions. 
Mean first-cycle SN-38 AUC was 99 ng/ml-hr in Arm A and 218 ng/ml-hr in Arm B. 
These AUCs are substantially lower than those in patients with colorectal cancer not receiving anticonvulsants. 
SN-38 exposure did not correlate with toxicity or response. 
In summary, CPT-11 as a single agent has demonstrable but limited antitumor activity in pts with recurrent glioma. 
While grade 4/5 toxicity can occur, toxicity is usually mild at the starting dose perhaps due to concomitant use of anticonvulsants. 
There was no definite association of total SN-38 exposure with toxicity or response.

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