Salvage chemotherapy with cyclophosphamide for recurrent temozolomide-refractory anaplastic astrocytoma

Authors

  • Marc C. Chamberlain M.D.,

    Corresponding author
    1. Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Center, Tampa, Florida
    • Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Center, 12902 Magnolia Dr., Suite 2010, Tampa, FL 33612
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    • Fax: (813) 745-3713

  • Denice D. Tsao-Wei M.S.,

    1. Department of Preventive Medicine, University of Southern California, Los Angeles, California
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  • Susan Groshen Ph.D.

    1. Department of Preventive Medicine, University of Southern California, Los Angeles, California
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Abstract

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. Cancer 2006. © 2005 American Cancer Society.

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