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Salvage chemotherapy with cyclophosphamide for
recurrent, temozolomide-refractory glioblastoma multiforme
Chamberlain MC, Tsao-Wei DD
Department of Neurology, University of Southern California/Norris
Comprehensive Cancer Center, Los Angeles, California 90033, USA.
chamberl@usc.edu
Background. The primary objective of the current prospective Phase II
study of cyclophosphamide (CYC) in adult patients with recurrent,
temozolomide-refractory glioblastoma multiforme was to evaluate 6-month
progression-free survival (PFS).
Methods. Forty patients (28 men and 12 women) ages 28-67 years (median
age, 51.5 years), with recurrent glioblastoma multiforme were treated.
All patients had been treated previously with surgery and involved-field
radiotherapy (median dose, 60 grays [Gy]; range, 59-61 Gy).
In addition, all patients were treated adjuvantly with either nitrosourea-based
chemotherapy (21 patients: procarbazine, lomustine, and vincristine in 13
patients; carmustine in 8 patients) or temozolomide (19 patients).
Twenty-one patients who were treated previously with a nitrosourea were treated
with temozolomide at the time of first recurrence.
Twenty-one patients were treated with CYC at the time of second recurrence, and
19 patients were treated with CYC at the time of first recurrence.
CYC was administered intravenously on 2 consecutive days (750 mg/m2 per day)
every 4 weeks (operationally defined as a single cycle).
Neurologic and neuroradiographic evaluations were performed every 8 weeks.
Results. All patients were evaluable.
In total, 170 cycles of CYC (median, 2 cycles; range, 2-12 cycles) were
administered.
CYC-related toxicity included alopecia in all patients (100%), anemia in 6
patients (3.5%), thrombocytopenia in 7 patients (4.1%), and neutropenia in 9
patients (5.3%).
Four patients required transfusions (two required red blood cell transfusion,
and two required platelet transfusion).
One patient developed neutropenic fever without bacteriologic
confirmation.
No treatment-related deaths occurred.
Seven patients (17.5%; 95% confidence interval [95% CI], 8-33%) exhibited a
neuroradiographic partial response, 11 patients (27.5%; 95% CI, 15-44%) had
stable disease, and 22 patients (55%) had progressive disease after a single
cycle of CYC.
The time to tumor progression ranged from 2 months to 18 months (median, 2
months).
Survival ranged from 3 months to 24 months (median, 4 months).
In patients with either a neuroradiographic response or stable disease (n = 18
[45%]), the median time to tumor progression was 6 months (range, 4-18 months;
95% CI, 6-8 months), and the median survival was 10 months (range, 5-24 months;
95% CI, 8-10 months).
The 6-month PFS rate was 20%.
Conclusions. CYC exhibited modest efficacy with acceptable toxicity in
the current cohort of adult patients with recurrent glioblastoma multiforme, all
of whom had previously experienced treatment failure after temozolomide
chemotherapy.
Copyright 2004 American Cancer Society.
PMID: 15022289 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15022289
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