Feasibility Study of Temozolomide Maintenance Therapy in Elderly Patients with AML Following Induction Therapy with High Dose Mitoxantrone and High Dose Ara-C.

With intensive chemotherapy, approximately 50% of elderly patients with AML achieve a complete remission, however essentially all will relapse within 2 years. To date, there is no standard effective postremission therapy for these patients, and most elderly patients tolerate multiple courses of intensive chemotherapy poorly. We previously demonstrated that temozolomide has significant antileukemic activity in patients with relapsed/refractory acute leukemia (Seiter K, et al JCO 2002). In that study 9/20 patients treated had a significant reduction in bone marrow blasts, and 4 patients had a formal complete response. Currently we are evaluating the feasibility and efficacy of temozolomide maintenance therapy administered after one cycle of intensive induction chemotherapy in elderly patients with newly-diagnosed AML. Induction consists of ara-C, 3 gm/m² daily for 5 days, and mitoxantrone, 80 mg/m² times one on day 2. Patients achieving complete remission then receive temozolomide 200 mg/m²/d for 7 days every 5 weeks until progression. To date, 34 pts have been treated: median age 69.5 (range 61–84); M/F: 21/13; prior AHD: 47%; cytogenetics: good: 1, intermediate: 24, poor: 7, insufficient: 2. Response to high-dose ara-C/high-dose mitoxantrone induction: CR: 56%, failure: 32%, toxic death: 12%. Two pts expired in remission unrelated to temozolomide: pneumonia, 1 pt, C. difficile colitis: 1 pt. Of 19 patients in CR, 16 received temozolomide maintenance. The median number of temozolomide cycles was 2 (range 1–14). 3 pts stopped temozolomide after 1 cycle (1 refused further therapy, 1 had stem cell transplant, 1 died from C. difficile colitis). Treatment was well tolerated and was administered in the outpatient setting. The median duration of remission is 6.8 months (95% CI: 4.5–9.1 months), and median survival is 5.5 months (95% CI: 3.7–7.3 months) for all patients and 10.1 months (95% CI: 4.9–15.2 months) for patients achieving CR. Temozolomide maintenance is feasible in patients with AML in CR. Further accrual is continuing to assess if remission duration and survival will be improved compared to historical controls.