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Initial chemotherapy in gliomatosis cerebri

From the Fédération de Neurologie Mazarin (Drs. Sanson, Taillibert, Napolitano, Djafari, Cougnard, Gervais, Laigle, Carpentier, Hoang-Xuan, and Delattre), Laboratoire de neuropathologie R Escourolle (Dr. Mokhtari), and Service de Neurochirurgie (Dr. Duffau), Groupe hospitalier Pitié-Salpêtrière and Université Pierre et Marie Curie, Paris, France; Neurologie B (Drs. Cartalat-Carel and Honnorat), Hopital Neurologique, Lyon, France; Service de Neurologie (Dr. Taillandier), Hôpital Central, CHU de Nancy, France; and Service de Neurochirurgie (Dr. Chinot), CHU la Timone, Université de la Méditerranée, Marseille, France.

Address correspondence and reprint requests to Marc Sanson, on behalf of the ANOCEF group, Fédération de neurologie Mazarin, Hôpital de la Salpêtrière, 47 Bd de l’Hôpital, 75013 Paris, France; e-mail: m.sanson{at}psl.ap-hop-paris.fr

Background: Because of the diffuse nature of gliomatosis cerebri (GC), surgery is not suitable, and large field radiotherapy carries the risk of severe toxicity. In this setting, initial chemotherapy warrants further investigation.

Methods: The authors treated 63 consecutive patients with GC with initial chemotherapy consisting of either PCV (procarbazine, 60 mg/m² on days 8 to 21; CCNU, 110 mg/m² on day 1; and vincristine, 1.4 mg/m² on days 8 and 29) or temozolomide (TMZ; 150 to 200 mg/m² for 5 days every 4 weeks). There were 40 men and 23 women, with a median age of 48 years (range, 17 to 74 years) and a median Karnofsky performance status of 90 (range, 50 to 100). GC was initially present at diagnosis in 49 patients (primary GC), whereas 14 patients with a circumscribed glioma at onset developed secondary GC after a median follow-up period of 5.11 years. GC was classified based on the predominant tumor cells as astrocytic, oligodendroglial, or mixed GC.

Results: Seventeen patients received 1 to 6 cycles (median, 5) of PCV, and 46 received 2 to 24 courses (median, 13) of TMZ. Grade 3 to 4 hematologic toxicity was seen in 4 of 17 (23.5%) patients treated with PCV and in 4 of 46 (8.6%) of those treated with TMZ. Clinical objective responses were observed in 21 of 63 (33%) patients, and radiologic responses were seen in 16 of 62 (26%), with no significant difference between the two regimens. For all patients combined, the median progression-free survival (PFS) and overall survival (OS) were 16 months and 29 months, respectively. Regardless of the chemotherapeutic regimen, oligodendroglial GC had a better prognosis than astrocytic and oligoastrocytic GC in terms of PFS (p < 0.02) and OS (p < 0.0001).

Conclusion: Initial chemotherapy is useful for some patients with gliomatosis cerebri. Temozolomide is well tolerated and appears to be a valuable alternative to procarbazine-CCNU-vincristine, especially for those with slow-growing, low-grade GC.

Received January 7, 2004. Accepted in final form March 26, 2004.

See also pages 205 and 354

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