Salvage chemotherapy with cyclophosphamide for recurrent temozolomide-refractory anaplastic astrocytoma

A prospective Phase II study of cyclophosphamide (CYC) was conducted in adult patients with recurrent temozolomide-refractory anaplastic astrocytoma (AA) with a primary objective of evaluating 6-month progression-free survival (PFS).

Forty patients (28 men, 12 women) ages 26-57 years (median, 43 yrs) with neuroradiographically recurrent AA were treated. All patients had previously been treated with surgery and involved-field radiotherapy. Additionally, all patients were treated with temozolomide (TMZ) chemotherapy after radiotherapy. All patients were treated at recurrence with CYC administered intravenously on 2 consecutive days (750 mg/m2/day) every 4 weeks (operationally defined as a single cycle). Neurologic and neuroradiographic evaluation were performed every 8 weeks.

All patients were evaluable. A total of 215 cycles of CYC (median, 4 cycles; range 2-12 cycles) was administered. CYC-related toxicity included alopecia (all patients, 100%), anemia (5, 12.5%), thrombocytopenia (6, 15%), and neutropenia (8, 20%). Four (10%) patients required transfusion. Nine patients (22.5%) (95% confidence interval [95% CI], 11%-39%) demonstrated a neuroradiographic partial response, 16 patients (40.0%) (95% CI, 25%-57%) demonstrated stable disease, and 15 patients (37.5%) (95% CI, 23%-54%) had progressive disease after 2 cycles of CYC. Time to tumor progression ranged from 2-19 months (median, 4 mos; 95% CI, 2-6 mos). Survival ranged from 2-26 months (median, 8 mos; 95% CI, 6-10 mos). The 6-month and 12-month PFS was 30% and 8%, respectively.

CYC demonstrated modest efficacy with acceptable toxicity in this cohort of adult patients with recurrent anaplastic astrocytoma, all of whom had failed prior TMZ chemotherapy.