Salvage chemotherapy with cyclophosphamide for recurrent temozolomide-refractory anaplastic astrocytoma.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Chamberlain
Marc C
MC
Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Center, Tampa, Florida 33612, USA. chamberl@moffitt.usf.edu
Tsao-Wei
Denice D
DD
Groshen
Susan
S
D000328:Adult; D000708:Anaplasia; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011446:Prospective Studies; D016879:Salvage Therapy; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D003520:Cyclophosphamide; D000077204:Temozolomide