Table 4.
Summary of articles describing the use of concomitant therapy of BCNU-impregnated wafers and other treatments, including modifications of the Stupp regimen
| Study | Year | Study Phase | Description | Design | N (GBM) | Median OS (mo) | Conclusion/Comments/Complications |
|---|---|---|---|---|---|---|---|
| Affronti et al92 | 2009 | Retrospective | Newly diagnosed | (1) Resection + BCNU wafer → RT + TMZ + rotational chemotherapy (2) Resection → RT + TMZ + rotational chemotherapy |
36 (36) 49 (49) |
16.7 20.6 |
31% grade 3 or 4 hematological toxicity 16% grade 3 or 4 hematological toxicity |
| Asher et al93 | 2007 | Phase II, single arm | Newly diagnosed | Resection + BCNU wafer → early TMZ (day 4) → Stupp regimen | 46 (43) | 18.2 | 33% of patients who received TMZ 200 mg/m2 experienced grade 3–4 thrombocytopenia compared with 5% who received 150 mg/m2 |
| Ewelt et al94 | 2008 | Retrospective | Recurrent | Resection + BCNU wafer → TMZ 1 week on/1 week off | 25 (25) | 18 (from initial diagnosis) | Ten patients with grade 3 and 6 patients with grade 4 toxicity |
| Gururangan et al95 | 2001 | Phase I | Recurrent | Resection + BCNU wafer → TMZ up to 12 cycles | 10 (7) | – | Median of 3 TMZ cycles administered 1 patient experienced grade 3 thrombocytopenia at the highest dose level |
| Limentani et al96 | 2005 | Phase I | Newly diagnosed | Resection + BCNU wafer → early (day 3 or 4) carboplatin → RT | 16 (14) | 22.3a | No grade 3 or 4 toxicities occurred |
| McPherson et al97 | 2012 | Phase I | Newly diagnosed | Resection + I-125 seeds (3000 cGy) + BCNU wafers → RT + adjuvant TMZ | 5 (5) | 12 | Dose-escalation study closed because of radiation toxicity |
| Quinn et al98 | 2009 | Phase II single arm | Recurrent | GTR + BCNU wafer → O6-BG | 52 (52) | 11.6a | Treatment-related toxicity included grade 3 hydrocephalus (9.6%), grade 3 CSF leak (19.2%), and grade 3 CSF/brain infection (13.4%) |
| Rezazadeh et al102 | 2011 | Phase II | Newly diagnosed | Resection + BCNU wafer → dense-dose RT + TMZ → bevacizumab every other week for 12 weeks | 10 (10) | – | 2 patients experienced intracranial hemorrhage and 1 experienced neutropenic fever Through median follow-up of 9 months, 6 patients experienced progression of disease and 6 patients died |
| Salmaggi et al99 | 2013 | Phase II, single arm | Newly diagnosed | Resection + BCNU wafer → RT + TMZ → daily metronomic TMZ 75 mg/m2 up to 6 months | 35 (35) | 17.8 | 7 patients had to prematurely stop TMZ due to toxicity DVT (n = 4) and/or PE (n = 1) occurred in 4 cases |
| Sampath et al100 | 2005 | Phase I | Recurrent | GTR + BCNU wafer → Irinotecan up to 6 cycles | 10 (10) | 20 | Mean number of Irinotecan cycles: 2.7 Median survival from the time of the second surgery was 13.5 months |
| Smith et al101 | 2008 | Phase II | Newly diagnosed | Resection + BCNU wafer → Gamma knife surgery → RT | 27 (27) | 11.5a | No acute early toxicity or complications within the first 3 months |
| Weingart et al103 | 2007 | Phase I | Recurrent | GTR + BCNU wafer → O6-BG | 32 (32) | 11.6a | No treatment-related grade 4 events 10 patients experienced grade 3 CSF leak and 7 patients experienced grade 3 CSF infection |
Abbreviations: BCNU, 1,3-bis(2-chloroethyl)-1- nitrosurea; DVT, deep-vein thrombosis; GTR, gross total resection; HGG, high-grade glioma; MGMT, O(6)-methylguanine-DNA methyltransferase; OS, overall survival; PE, pulmonary embolism; PFS, progress-free survival; RT, radiation therapy; TMZ, temozolamide.
a = days or weeks converted to months.