Treatment > Methotrexate  

Meeting Abstract

CLIMT-2: an ongoing phase-II multicentre trial of MATILde chemotherapy regimen (methotrexate-cytarabine-thiotepa-idarubicin) in HIV-negative primary CNS lymphomas (PCNSL)

Andrés J Ferreri, Massimo Bernardi, Stefania Dell'Oro, Alba A Brandes, Michele Reni, Fabio Ciceri, Lara M Pasetto, Michele Spina, Caterina Stelitano, Monica Balzarotti, Fiorella Ilariucci, Maurilio Ponzoni, Alberto Franzin, Romano Danesi, Eugenio Villa

Depts of Radiochemotherapy, Hematology, Pathology, and Neurosurgery, San Raffaele H Scientific Institute, Milan, Italy; Div of Hematology, Osp. di Padova, Milan, Italy; Div of Oncology, Osp. di Padova, Padova, Italy; Div of Medical Oncology A, National Cancer Institute, Aviano, Italy; Div of Hematology, Osp. di Reggio Calabria, Reggio Calabria, Italy; Div of Oncology, Istituto Clinico Humanitas, Rozzano, Italy; Div of Hematology, Osp. di Reggio Emilia, Reggio Emilia, Italy; Div of Oncology, University of Pisa, Pisa, Italy

Purpose. To assess activity and feasibility of MATILde chemotherapy regimen in PCNSL.

Patients & methods. Untreated HIV-negative pts (<=70 years, ECOG-PS<4) with pathological diagnosis of lymphoma and CNS-limited disease are eligible to receive 3 courses of methotrexate 3.5 g/m² d.1; idarubicin 15 mg/m² d.1; cytarabine 2 g/m²x2/d d.2; and thiotepa 25 mg/m² d.3; every three weeks.
Pts achieving a complete remission (CR) or partial remission >90% (PR₁) do not receive further treatment.
Pts with PR₂, stable (SD) or progressive disease (PD) receive whole-brain irradiation (36-40 Gy).
Planned accrual (Α=0.05; β=0.2) to show a 30% improvement of CR rate is 46 pts.

Results. Nineteen pts (median age: 55) were registered since May 2000.
Four pts had a PS=3; 5 had elevated LDH levels.
All pts but one (meninges) had brain lesions, multiple in 8, without ocular involvement.
Tumor cells were detected in 3 of the 13 CSF-assessed pts, hyperproteinorrhachia in 8.
After 42 courses, toxicity consisted of G4 neutropenia (64% of courses), G4 thrombocytopenia without bleeding (50%), G4 anemia (7%), G2-3 infection (16%), and G3 venous thrombosis (12%).
Chemotherapy was interrupted in 4 cases (3 PR₂) due to persistent thrombocytopenia or early death (pulmonary thromboembolism, septic shock and unknown cause).
Fatal complications (FC) occurred in pts with PS=3.
Chemotherapy is ongoing in 3 cases.
Response rate was 88% after the first course of chemotherapy (n=17; 4 CR, 3 PR₁, 8 PR₂, 1 SD, 1 FC), and 63% after chemotherapy (n=16; 5 CR, 2 PR₁, 3 PR₂, 3 PD, 3 FC) and 69% after radiotherapy (8 CR, 3 PR₁, 2 PD, 3 FC).
Two pts with PD and two pts relapsed after radiotherapy died of lymphoma.
Two pts in CR after MATILde experienced early relapse; they were irradiated achieving a second CR (alive at 12 and 18 months).
Twelve pts are alive (median follow-up: 10 months).

Conclusions. MATILde is a feasible and active combination.
Accrual is ongoing.
Adequate anticoagulant prophylaxis is mandatory since the high risk of thromboembolism in pts with PS=3.

© Copyright 2002 American Society of Clinical Oncology