Treatment > Temozolomide Clinical Trials

Meeting Abstract

Safety and efficacy of temozolomide concomitant and sequential to radiotherapy in glioblastoma multiforme: Results of a phase II multicentric study

L. Fatigante, L. Cionini, A. M. Nocita, M. Luppatelli, A. Tagliagambe, F. Grillo Ruggeri, L. Pirtoli, A. Paccapelo

Radiotherapy University, PISA, Italy; Radiotherapy, Perugia, Italy; Radiotherapy, Carrara, Italy; Radiotherapy, Ancona, Italy; Radiotherapy, Siena, Italy; Division of Oncology, Ancona, Italy

Purpose. In January 2000 we started a multicentric phase II study in patients (pts) with newly diagnosed Glioblastoma Multiforme (GBM), to evaluate tolerability and efficacy of Temozolomide (TMZ) concurrent and sequential to Radiotherapy(RT).

Methods. 122 pts were enrolled, 79 male, 43 females, median age 60.7 years (34-84), median ECOG P.S. 1 (0-2).
Surgery was complete in 57 pts, incomplete in 48; 17 had biopsy only.
RT was delivered with ³4 Mv photons, multiple fields; total dose was 60 Gy, 2 Gy/fr, 5 days/week.
TMZ (75 mg/sqm/day) was given orally 7 days/week, 1 hour before RT.
In pts without progression of disease, as demonstrated by CT or MR, sequential TMZ started at the dose of 200 mg/sqm (6 cycles every 28 days).
121 pts completed the concomitant treatment (1 interrupted because of G3 thrombocytopenia), while only in 47 pts all the sequential program was performed.
8 pts are still on treatment and 8 interrupted because of refusal; in the remaining, the interruption was caused by: progression of disease (54), death for non neoplastic disease (4).

Results. The actuarial overall survival (OS) according to Kaplan-Meier was respectively at 12 and 24 months 72% and 38%.
38% of the overall pts were free from progression (FFP) at 12 months, 20% at 24 months.
In the 47 pts who completed the program, OS at 12 and 24 months was 98% and 57%, with Freedom From Progression 70% and 38%.
Treatment tolerance was good; main side effects were gastroenteric and haematologic.
During the concomitant treatment we observed: vomiting G1-G2 (21%), G3-G4 (4.7%); thrombocytopenia G2 (5.6%), G3-G4(3.8%).
3 pts discontinued sequential phase: in 1 case very severe vomiting at the 5th cycle occurred, the others 2 pts had haematologic toxicities (1 G4 thrombocytopenia and 1 G3 neutropenia).
A few pts presented a mild elevation of the hepatic function tests.

Conclusions. The compliance to this treatment protocol valuated in our experience was good, resulting feasible in more than 90% of cases, with moderate acute morbidity.
Both actuarial overall survival ant time to progression compare favourably with values reported usually in this neoplastic disease.

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