Salvage chemotherapy with cyclophosphamide for recurrent, temozolomide-refractory glioblastoma multiforme.

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Cancer. 2004 Mar 15;100(6):1213-20.

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.

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.