CHEMOTHERAPY FOR ANAPLASTIC OLIGODENDROGLIOMA

Purpose: To examine the rate and duration of response of anaplastic ol igodendrogliomas to a dose-escalated combination chemotherapy regimen consisting of procarbazine, lomustine (CCNU), and vincristine (PCV) an d to evaluate the side effects of this treatment. Methods: In this sin gle-arm multicentered phase II study, patients with measurable, newly diagnosed or recurrent contrast-enhancing anaplastic oligodendroglioma s were treated with up to six cycles of PCV. Central pathology and rad iology review were mandatory, and rigorous response criteria based on imaging were used. Results: Thirty-three patients entered the trial; n ine were excluded subsequently, seven due to ineligible pathology. Eig hteen of 24 eligible patients (75%) responded, nine completely (38%), four had stable disease (SD), and two progressed during the first cycl e of PCV. Responses were observed in nine of 10 patients (90%) with a preexisting low-grade oligodendroglioma and 10 of 15 (67%) with necrot ic tumors, called glioblastoma multiforme by some. previously irradiat ed patients were as likely to respond to PCV as those newly diagnosed (11 of 15 [73%] v seven of nine [78%]). The median time to progression will be at least 25.2 months for complete responders, and was 14.2 mo nths for partial responders and 6.8 months for stable patients. four i neligible patients also responded to PCV; all had gliomas with oligode ndroglial differentiation. All responders, eligible or ineligible, wer e stable or improved neurologically, but nine of 22 (41%) experienced a decline in Eastern Cooperative Oncology Group (ECOG) performance sta tus of one grade while on PCV. Adverse events on treatment included ct death from Pneumocystis pneumonia, ct severe reversible encephalopath y due to procarbazine, an intratumoral hemorrhage, and a subdural hema toma. All other acute toxicities were anticipated and manageable. Conc lusion: Anaplastic oligodendrogliomas are chemosensitive cancers. Pati ents with these tumors respond predictably, durably, and often complet ely to PCV, and many tolerate a dose-escalated formulation, Cooperativ e group and randomized trials will be necessary to explore fully the r ole of chemotherapy in the treatment of aggressive oligodendrogliomas.