Karen[a]
Second line BCNU plus CPT-11 chemotherapy in recurrent glioblastoma (GBM): Phase II study of GICNO (Italian Neuro-Oncology Group).
Abstract No: 1516
Author(s): A. A. Brandes, A. Tosoni, M. Reni, F. Valduga, U. Basso, S. Lonardi, L. M. Pasetto, V. Blatt, S. Monfardini, M. Ermani; Azienda Ospedale-Università, Padova, Italy; San Raffaele H., Milan, Italy; Santa Chiara H., Trento, Italy
Background:
In a phase I study the MTD of CPT-11 associated with BCNU was established at 225 mg/m2 for patients (pts) on p450 enzyme inducing anticonvulsants (EIAC). The aim of the present phase II study was to evaluate PFS at 6 months (PFS-6), time to progression (TTP), response rate (RR) and toxicity of associated BCNU and CPT-11.
Methods:
From August 2001 to October 2003, 42 pts (29 M, 13 F; mean age 53 yrs, range 27-71 yrs) and on EIAC with recurrent/progressive GBM after surgery, radiotherapy and first line chemotherapy with temozolomide, were given chemotherapy with BCNU 100 mg/m2 every 6 weeks on day 1 plus CPT-11 weekly for 4 weeks (starting dose 175 mg/m2), followed by 2-weeks' rest. Second cycle CPT-11 was escalated to 200 mg/m2 if no G2 toxicity was registered.
Results: PFS-6 was 30.3% (95% CI: 18.5% - 49.7%) and TTP 17.27 weeks (95% CI: 11.9 - 23.9). Age <45 years (p=0.024) and response to chemotherapy (p<0.001) were independent prognostic factors. Nine pts (21.4%, 95% CI: 9% - 34%) had a partial response (PR), and 21 (50%, 95% CI: 35% - 65%), stable disease. A total of 130 cycles was delivered (mean 3.1 per pt, range 1-8). The CPT-11 dose was escalated to 200 mg/m2 in 26 cycles (20%), and reduced to 75% in 22 cycles (17%) because G2 diarrhea (59%) and neutropenia ≥G2 (41%) occurred; 2.4% of the pts had G3 neutropenia. Nausea and vomiting were G3 in 4 pts (9.5%), and diarrhea G1-2 in 29 pts (69%) and G3 in 3 pts (7.1%). Therapy was discontinued in 2 pts (4.8%) that had G3 pulmonary toxicity while they were on PR. Overall MST was 11.7 months (95% CI: 7.4-NA).
Conclusions; This new regimen is highly active as second line chemotherapy in pts with recurrent GBM with an acceptable toxicity. Further studies are therefore warranted to test it as first line chemotherapy.
Event: 2004 ASCO Annual Meeting
Presenter: Alba Ariela Brandes, MD