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Pegylated liposomal
doxorubicin plus temozolamide in the salvage treatment of brain metastases: The
update
M. Caraglia, R. Addeo, R. Costanzo, L. Montella, V. Faiola, E. Capasso, S.
Del Prete
S. Giovanni di Dio Hospital, Frattamaggiore, Italy
Background.
It has been recently demonstrated that pegylated liposomal
doxorubicin (Caelyx, PLD) can cross the brain-blood barrier with a consequent
accumulation in primitive and secondary brain tumours.
Moreover, temozolamide (TMZ) is a new imidazo-tetrazine
that accumulates in brain tissue and is used alone or in combination with
radiotherapy in the treatment of primary and secondary brain tumours.
The two drugs have been already used in combination in a
phase I cinical study in the treatment of advanced solid tumours.
Methods.
We have evaluated the feasibility of the concomitant
administration of TMZ and PLD in the treatment of brain mestastases and a
preliminary evaluation of the activity was also performed.
We have treated 12 consecutive patients (7 F and 5 M, mean
age: 62.83 + 13.9 yrs; median age: 65.5 yrs) affected by brain metastases
from different solid tumours (4 breast adenocarcinoma, 6 non small lung cancer,
1 melanoma, 1 ovarian cancer) with TMZ 1000 mg/m2 fractionated in 5
days and PLD 40 mg/m2 day 1 every 28 days.
Nine out of 12 pts. have received previous whole brain
irradiation plus TMZ.
Results.
Thirty-four cycles were performed.
Three grade II ad 8 grade I neutropenia (CTC), 2 grade II
hand and foot syndrome, 8 grade I thrombocytopenia and 9 grade I alopecia were
recorded.
Nausea and vomiting or liver or renal toxicity were never
observed in our series being the schedule well tolerated in all patients.
Two CR and two PRs was recorded in the four patients with
breast tumours, while a clinical benefit was achieved in other 4 patients (1
with melanoma and 3 with lung cancer).
In the long-surviving pt. (overall survival, OS: 27+
months), who achieved CR, also a remission of a neoplastic pleural effusion was
observed.
Other 2 still alive pts. (breast and NSCLC, respectively),
who achieved a PR and a SD, had an OS of 14 and 9 months, respectively.
Conclusions.
the schedule was a well tolerated treatment (also in elder
pts.) and has suggested an encouraging activity in brain metastases from breast.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-001560,00.asp
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