Table 1.
Key trials supporting the current neoadjuvant, adjuvant and metastatic chemotherapy regimens.
| Chemotherapy | Trial characteristics |
Outcomes | Reference | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase | N | R | Line | ||||||||
| Neoadjuvant | Response rates | Survival outcomes (months) | |||||||||
| MVAC versus cystectomy or RT alone (T2 to T4aN0) |
III | 317 | Y | 1st | MVAC
cystectomy alone |
↓pT0 = 38%
↓pT0 = 15% p<0.001 |
MVAC
Cystectomy/RT alone (months) |
MS
MS |
77
46 p=0.06 |
Grossman et al. (2003) | |
| CMV versus cystectomy alone (T2 to T4aN0) |
III | 976 | Y | 1st | CMV | ↓pT0 = 32.5% | CMV
cystectomy alone (10-year f/u) |
OS
OS |
36%
30% |
International Collaboration of Trialists (1999) | |
| AMVAC
(cT2-T4a and N0-1) |
II | 44 | N | 1st | AMVAC | ↓pT0 = 38%
↓pT1 = 14% |
Plimack et al. 2014 | ||||
| AMVAC
(cT2-cT4, N0-1) |
II | 39 | N | 1st | AMVAC | PaR ≤ pT1 in 49% | with PaR
without PaR |
1 yr DFS | 89%
67% |
Choueiri et al. (2014) | |
| Adjuvant | 5-year recurrence outcomes | 5-year survival outcomes | |||||||||
| GC versus chemo at relapse (T2G3, T3 to T4, N0-2) |
III | 194 | Y | 1st | GC
chemo at relapse |
DFS
DFS |
42.3%
37.2% p=0.70 |
GC
Chemo at Relapse |
OS
OS |
53.7%
43.4% p=0.24 |
Cognetti et al. (2012) |
| MVAC versus observation (T1 and T2N0) |
III | 114 | Y | 1st | MVAC
observation |
TTR | 0.20; p=0.62; HR=0.78 | MVAC
observation |
OS
OS |
85%
85% |
Stadler et al. (2011) |
| AMVAC/GC/MVAC versus chemo at relapse (T3 to T4 and/or N+M0) |
III | 284 | Y | 1st | adjuvant chemo
chemo at relapse |
PFS
PFS |
31.8%
47.6% p<0.05 |
adjuvant chemo
chemo at relapse |
OS
OS |
47.7%
53.6% p=0.13 |
Sternberg et al. (2015) |
| Metastatic | Response rates | Survival outcomes (months) | |||||||||
| MVAC versus cisplatin | III | 269 | Y | 1st | MVAC
Cisplatin |
ORR
ORR |
39%
12% |
MVAC
Cisplatin |
PFS
OS PFS OS |
10.0
12.5 4.3 8.2 |
Loehrer et al. (1992) |
| GC versus MVAC | III | 405 | Y | 1st | GC
MVAC |
CR PR ORR CR PR ORR |
12.2%
37.2% 49.4% 11.9% 33.8% 45.7% |
GC
MVAC |
PFS
MS 5-yr OS PFS MS 5-yr OS |
7.7
14.0 13.0% 8.3 15.2 15.3% |
Von der Maase et al. (2005) |
| Classical MVAC versus AMVAC | III | 263 | Y | 1st | MVAC | CR
PR ORR |
9%
41% 50% |
MVAC | PFS
MS 5-yr OS |
8.1
14.9 13.5% |
Sternberg et al. (2006) |
| AMVAC | CR
PR ORR |
21%
41% 64% |
AMVAC | PFS
MS 5-yr OS |
9.5
15.1 21.8% |
||||||
Abbreviations: N, number randomized; R, randomized; Y, yes; N, no; MVAC, methotrexate, vinblastine, doxorubicin, cisplatin; MS, median survival; CMV, cisplatin, methotrexate, vinblastine; OS, overall survival; MRC, Medical Research Council; EORTC, European Organization for Research and Treatment of Cancer; AMVAC, accelerated MVAC; PaR, pathologic response; GC, gemcitabine, cisplatin; DFS, disease free survival; TTR, time to recurrence; PFS, progression-free survival; ORR, overall response rate; CR, complete response; PR, partial response; RT, radiation therapy.