|
|
A phase I study
of chemo-radiotherapy using gemcitabine as a radiosensitiser in patients with
metastases to the brain
J. Sgouros, S. Upadhyay, M. Braun, M. Holmes, A. Maraveyas
Academic Oncology Princess Royal
Hospital, Hull, United Kingdom; Clinical Oncology Princess Royal Hospital, Hull,
United Kingdom
Background. Conventional treatment for patients with brain metastases is
whole-brain radiotherapy (WBRT).
Efficacy is poor and median survival for these patients is 2-3 months.
One way to increase the efficacy of radiotherapy (RT) is to use a
radiosensitising agent.
Gemcitabine (gem) is a potent radiosensitiser.
There is also some evidence that it crosses the blood-brain barrier.
The primary objective of this study was to determine the maximum tolerated dose
(MTD) of gem when given in conjunction with WBRT.
Methods. Patients with brain
metastases and fit for RT were included in the study.
Adequate haematological, renal and liver functions and clinical stability on
steroids were required.
WBRT was 30Gy in 10 daily fractions.
Gem was given 2-4 hours prior to RT on day 1 and 8 of the first cohort of
patients and then day 1, 4, 8 and 11 subsequently.
Starting dose was 25mg/m2, escalated by 12.5mg/m2increments.
At least 3 patients were included per level.
Dose limiting toxicity (DLT) was defined as grade 4 haematological toxicity or
grade ≥ 3 non-haematological toxicity.
Results. 25 patients were
entered in the study.
15 male, 10 female.
74% had a PS 1 (WHO).
Twelve had NSCLC, 6 colorectal, 4 breast cancer, 2 renal cell carcinoma and 1
oesophageal carcinoma.
92% had concurrent extracranial disease.
Six had a single brain metastasis, 13 had 2 or 3 metastases and 6
multiple.
Up to 50mg/m2 (level 4) no DLT was observed but at this level 6 out
of 7 patients had at least one dose reduced or omitted due to toxicity.
At level 5 (62.5mg/m2) and at level 6 (75mg/m2) 1 out of 6
and 1 out of 2 patients developed DLT (thrombocytopenia-bleeding and neutropenic
sepsis).
Conclusions. The MTD of gem in
this schedule is 62.5mg/m2.
A phase II study evaluating the efficacy of the regime has commenced.
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_19-001424,00.asp
|
