Table 2.
Select trials of WBRT with concurrent systemic agents for brain metastases
| Studya | Systemic Agent | Primary Cancer | Trial Design | N | WBRT Dose | Primary Endpoint | Overall Survival | CNS Response Rate (CR + PR) in Evaluable Patients | Other Outcomes |
|---|---|---|---|---|---|---|---|---|---|
| Guerrieri et al, 2004161 | Carboplatin | NSCLC | Phase III randomized controlled trial (stopped prematurely due to poor accrual) | G1: WBRT (N = 21), G2: WBRT + carboplatin (N = 21) |
20 Gy in 5 fractions | Overall survival | G1: 4.4 mo G2: 3.7 mo (P = NS) |
G1: 10% G2: 29% (P = NS) |
|
| Ushio et al, 1991162 | Chloroethylnitrosureas tegafur | Lung | Phase III randomized controlled trial | G1: WBRT (N = 25) G2: WBRT + chloroethylnitrosureas (N = 34) G3: WBRT + chloroethylnitrosureas + tegafur (N = 29) |
40 Gy in 1.5–2 Gy fractions | Tumor control | G1: 27 wk G2: 29 wk G3: 30.5 wk (P = NS) |
G1: 36% G2: 69% G3: 74% G1 vs G2 (P = NS) G2 vs G3 (P = NS) G1 vs G3 (P < .05) |
|
| Margolin et al, 200288 | Temozolomide | Melanoma | Phase II single arm trial | N = 31 | 30 Gy in 3 Gy fractions | Objective response | 6 mo | 10% | |
| Antonadou et al, 2002163 | Temozolomide | Lung, breast, or unknown primary | Phase II randomized trial | G1: WBRT (N = 23) G2: WBRT + concurrent TMZ followed by 6 cycles of adjuvant TMZ (N = 25) |
40 Gy in 2 Gy fractions | RR and neurologic symptom evaluation | G1: 7.0 mo G2: 8.6 mo (P = NS) |
G1: OR 67% G2: OR 96% (P = .017) |
Improvement in neurologic function in the TMZ group |
| Verger et al, 2005164 | Temozolomide | Multiple (∼50% lung, 15% breast) | Phase II randomized trial (stopped prematurely due to poor accrual) | G1: WBRT (N = 41) G2: WBRT + concurrent TMZ followed by 2 cycles of adjuvant TMZ (N = 41) |
30 Gy in 3 Gy fractions | Neurologic toxicity | G1: 3.1 mo G2: 4.5 mo (P = NS) |
Response at 30 d G1: OR 32% G2: OR 32% (P = NS) |
Freedom from intracranial progression at 90 d was improved in the TMZ group |
| Sperduto et al, 201287 | Temozolomide or erlotinib | NSCLC | Phase III randomized trial | G1: WBRT + SRS (N = 44) G2: WBRT + SRS + TMZ (N = 40) G3: WBRT + SRS + erlotinib (N = 41) |
WBRT: 37.5 Gy in 2.5 Gy fractions SRS dose was size dependent: lesions < 2 cm, 2.1 to 3.0 cm, and 3.1 to 4.0 cm received 24, 18, and 15 Gy, respectively |
Overall survival | G1: 13.4 mo G2: 6.3 mo G3: 6.1 mo (P = NS for G1 vs G2 and G1 vs G3) |
Not reported | No difference between groups in time to CNS progression Grade 3–5 toxicity rates were 11% in G1, 41% in G2, and 49% in G3; high toxicity rates may have led to inferior survival in the combination arms |
| Welsh et al, 201386 | Erlotinib | NSCLC | Phase II single-arm trial | N = 40 | 35 Gy in 2.5 Gy fractions | Overall survival | 11.8 mo | 86% | No grade 4–5 toxicities Median survival was 19.1 vs 9.3 mo for patients with vs without an EGFR mutation |
| Knisely et al, 2008 (RTOG 0118)165 | Thalidomide | Multiple (∼60% lung) | Phase III randomized trial | G1: WBRT (N = 93) G2: WBRT + thalidomide (N = 90) |
37.5 Gy in 2.5 Gy fractions | Overall survival | G1: 3.9 mo G2: 3.9 mo |
Not reported | No difference between arms in time to progression or rate of death due to brain metastases. 48% patients discontinued thalidomide due to side effects |
| Neuhaus et al, 2009166 | Topotecan | Lung | Phase III randomized trial (stopped prematurely due to poor accrual | G1: WBRT (N = 49) G2: WBRT + topotecan (N = 47) |
20 Gy in 2 Gy fractions | Overall survival | G1: 95 d G2: 87 d (P = NS) |
Response 2 wk after treatment G1: 52% G2: 60% |
No difference between groups in progression free survival |
Abbreviations: CR, complete response; PR, partial response; OR, odds ratio. aArranged according to systemic agent and study design.