Intra-arterial carboplatin as a salvage strategy in the treatment of recurrent glioblastoma multiforme
- 390 Downloads
The first-line treatment of glioblastoma typically consists of a maximal surgical resection, followed by a combination of radio-chemotherapy with temozolomide. There is however no consensus regarding optimal therapeutic approaches at relapse. The following phase II study explored the therapeutic gain obtained when exposing these patients to a combination of intra-arterially administered carboplatin and melphalan at first or second relapse as a salvage treatment in recurrent glioblastoma. Fifty-one consecutive patients diagnosed with glioblastoma were accrued and offered this treatment at first or second relapse. A Karnofsky score of ≥60 was required, and when appropriate, patients were first reoperated prior to accrual. Patients enrolled were treated every 4 weeks (1 cycle) for up to 12 cycles. Progression was evaluated by Macdonald criteria. Primary end point surrogates were overall survival from diagnosis and study entry. Median survival from diagnosis and study entry was 23 and 11 months, respectively. The median time to progression was 5.2 months. All patients enrolled were treated for a minimum of 2 cycles. Hematologic toxicity was manageable, with an 8 % of grade II neutropenia, 12 % of grade II thrombocytopenia and 7 % of grade III thrombocytopenia. This therapeutic strategy represents an adequate option in the second-line treatment of recurrent glioblastoma. The adjunction of an osmotic permeabilization could be considered to further expand delivery, and hopefully improve survival in these patients.
KeywordsIntra-arterial chemotherapy Carboplatin Glioblastoma Recurrent glioblastoma Salvage treatment
This work was supported by the National Bank research chair on brain tumors, held by D. Fortin. The protocol was approved by the institutional review board, and informed consent was obtained for each patient in accordance to institutional regulation prior to accrual.
Conflict of interest
The authors have no financial disclosure and there is no conflict of interest to declare.
- 26.Boulikas T (2007) Molecular mechanisms of cisplatin and its liposomally encapsulated form, LipoplatinTM. LipoplatinTM as a chemotherapy and antiangiogenesis drug. Cancer Ther 5:349–376Google Scholar
- 39.Charest G, Sanche L, Fortin D, Mathieu D, Paquette B (2012) Glioblastoma treatment: bypassing the toxicity of platinum compounds by using liposomal formulation and increasing treatment efficiency with concomitant radiotherapy. Int J Radiat Oncol Biol Phys. doi: 10.1016/j.ijrobp.2011.10.054 PubMedCentralPubMedGoogle Scholar
- 42.Jiglaire CJ, Baeza-Kallee N, Denicolaï E, Barets D, Metellus P, Padovani L et al (2013) Cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening. Exp Cell Res 12:1–10Google Scholar