ACNU-based chemotherapy for recurrent glioma in the temozolomide era

Abstract

No standard of care for patients with recurrent glioblastoma has been defined since temozolomide has become the treatment of choice for patients with newly diagnosed glioblastoma. This has renewed interest in the use of nitrosourea-based regimens for patients with progressive or recurrent disease. The most commonly used regimens are carmustine (BCNU) monotherapy or lomustine (CCNU) combined with procarbazine and vincristine (PCV). Here we report our institutional experience with nimustine (ACNU) alone (n = 14) or in combination with other agents (n = 18) in 32 patients with glioblastoma treated previously with temozolomide. There were no complete and two partial responses. The progression-free survival (PFS) rate at 6 months was 20% and the survival rate at 12 months 26%. Grade III or IV hematological toxicity was observed in 50% of all patients and led to interruption of treatment in 13% of patients. Non-hematological toxicity was moderate to severe and led to interruption of treatment in 9% of patients. Thus, in this cohort of patients pretreated with temozolomide, ACNU failed to induce a substantial stabilization of disease in recurrent glioblastoma, but caused a notable hematotoxicity. This study does not commend ACNU as a therapy of first choice for patients with recurrent glioblastomas pretreated with temozolomide. (PCV). Here we report our institutional experience with nimustine (ACNU) alone (n=14) or in combination with other agents (n=18) in 32 patients with glioblastoma treated previously with temozolomide. There were no complete and two partial responses. The progression-free survival (PFS) rate at 6 months was 20% and the survival rate at 12 months 26%. Grade III or IV hematological toxicity was observed in 50% of all patients and led to interruption of treatment in 13% of patients. Non-hematological toxicity was moderate to severe and led to interruption of treatment in 9% of patients. Thus, in this cohort of patients pretreated with temozolomide, ACNU failed to induce a substantial stabilization of disease in recurrent glioblastoma, but caused a notable hematotoxicity. This study does not commend ACNU as a therapy of first choice for patients with recurrent glioblastomas pretreated with temozolomide.

Nonsurgical Treatment of Recurrent Glioblastoma

“…Temozolomide is now the accepted standard for firstline treatment. Nimustine in monotherapy in pre-treated patients or in combination with teniposide or cytarabine has yielded a 6-month pfs (pfs-6) of 20%, with a median os of 6.7 months 16 .…”

Canadian Recommendations for the Treatment of Recurrent or Progressive Glioblastoma Multiforme

“…The combination of fotemustine-procarbazine may provide some benefit with respect to partial response and stable disease, but it does not appear to improve 6-month pfs 103 . The use of nimustine is not advised because of its modest efficacy and high rate of hematologic toxicity 109 . Salvage cyclophosphamide at the time of first or second recurrence post-temozolomide has also been reported to have modest efficacy (6-month pfs: 20%) with more acceptable toxicity 110 .…”

An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting

“…However, a phase II trial employing such a combination resulted in comparable results to that of CPT-11 alone and increased toxicity [68]. Similarly, ACNU, another nitrosourea given alone or in combination with teniposide or cytarabine in patients with GBM after TMZ failure resulted in limited activity and considerable toxicity [69]. The combination of CPT-11 and celecoxib, a selective COX-2 inhibitor was well tolerated and had a marginal activity against heavily pretreated recurrent glioma (mostly GBM) patients with PFS6 of 25.1% [70].…”