Rahman Rifaquat, Hempfling Kelly, Norden Andrew D, Reardon David A, Nayak Lakshmi, Rinne Mikael L, Beroukhim Rameen, Doherty Lisa, Ruland Sandra, Rai Arun, Rifenburg Jennifer, LaFrankie Debra, Alexander Brian M, Huang Raymond Y, Wen Patrick Y, Lee Eudocia Q
Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
Neuro Oncol. 2014 Nov;16(11):1523-9. doi: 10.1093/neuonc/nou118. Epub 2014 Jun 23.
Currently, there are no known effective treatments for recurrent glioblastoma once patients have progressed on a bevacizumab-containing regimen. We examined the efficacy of adding nitrosoureas to bevacizumab in patients who progressed while on an initial bevacizumab-containing regimen.
In this retrospective study, we identified adult patients with histologically confirmed glioblastoma (WHO grade IV) who were treated with lomustine or carmustine in combination with bevacizumab as a second or third regimen after failing an alternative initial bevacizumab-containing regimen. Response rate (RR), 6-month progression free survival (PFS6), and progression-free survival (PFS) were assessed for each treatment.
Forty-two patients were identified (28 males) with a median age of 49 years (range, 24-78 y). Of 42 patients, 28 received lomustine (n = 22) or carmustine (n = 6) with bevacizumab as their second bevacizumab-containing regimen, and 14 received lomustine (n = 11) or carmustine (n = 3) as their third bevacizumab-containing regimen. While the median PFS for the initial bevacizumab-containing regimen was 16.3 weeks, the median PFS for the nitrosourea-containing bevacizumab regimen was 6.3 weeks. Patients had an RR of 44% and a PFS6 rate of 26% during the initial bevacizumab regimen and an RR of 0% and a PFS6 rate of 3% during the nitrosourea-containing bevacizumab regimen. There was increased grade 3-4 toxicity (45% vs 19%, P = .010) during the nitrosourea-containing bevacizumab regimen relative to the initial bevacizumab regimen. Median overall survival was 18.7 weeks from initiation of the nitrosourea-containing bevacizumab regimen.
The addition of lomustine or carmustine to bevacizumab after a patient has already progressed on a bevacizumab-containing regimen does not appear to provide benefit for most patients and is associated with additional toxicity with the doses used in this cohort.
目前，对于复发性胶质母细胞瘤患者，一旦其在含贝伐单抗的治疗方案中病情进展，尚无已知的有效治疗方法。我们研究了在初始含贝伐单抗治疗方案中病情进展的患者，在贝伐单抗基础上加用亚硝基脲的疗效。
在这项回顾性研究中，我们纳入了组织学确诊为胶质母细胞瘤（世界卫生组织IV级）的成年患者，这些患者在含贝伐单抗的初始替代治疗方案失败后，接受洛莫司汀或卡莫司汀联合贝伐单抗作为第二或第三种治疗方案。评估每种治疗的缓解率（RR）、6个月无进展生存期（PFS6）和无进展生存期（PFS）。
共纳入42例患者（28例男性），中位年龄49岁（范围24 - 78岁）。42例患者中，28例接受洛莫司汀（n = 22）或卡莫司汀（n = 6）联合贝伐单抗作为含贝伐单抗的第二种治疗方案，14例接受洛莫司汀（n = 11）或卡莫司汀（n = 3）作为含贝伐单抗的第三种治疗方案。初始含贝伐单抗治疗方案的中位PFS为16.3周，而含亚硝基脲的贝伐单抗治疗方案的中位PFS为6.3周。患者在初始贝伐单抗治疗方案期间的RR为44%，PFS6率为26%；在含亚硝基脲的贝伐单抗治疗方案期间的RR为0%，PFS6率为3%。相对于初始贝伐单抗治疗方案，含亚硝基脲的贝伐单抗治疗方案期间3 - 4级毒性增加（45%对19%，P = 0.010）。从含亚硝基脲的贝伐单抗治疗方案开始，中位总生存期为18.7周。
在患者已在含贝伐单抗治疗方案中病情进展后，在贝伐单抗基础上加用洛莫司汀或卡莫司汀对大多数患者似乎并无益处，且与该队列中使用的剂量所带来的额外毒性相关。
