Rationale for superseding:
There is no evidence demonstrating equivalent efficacy for day 8 dosing of carboplatin vs the day 1 schedule. Whilst a small phase II study did demonstrate fewer dose adjustments with day 8 carboplatin, no difference in outcomes were notedr, and carboplatin/gemcitabine regimens across several malignancies have continued to administer carboplatin on day 1. For this reason the Medical Oncology Reference Committee has superseded this protocol.
Cisplatin and gemcitabine or MVAC remain the standard systemic regimen for metastatic or locally advanced TCC of the urothelium. However, this cancer commonly occurs in an elderly population often with multiple co-morbidities and these cisplatin-based regimens may be poorly tolerated, particularly in those with a poor performance status or in the very elderly. A number of phase 2 studies have examined the substitution of carboplatin for cisplatin, suggesting better tolerability and response rates of 30 to 60%.rrr
There are no randomised studies of gemcitabine + carboplatin or cisplatin. However, a study of 47 patients of MVAC vs carboplatin based regimen (M-CAVI) showed an overall response rates of 39% for M-CAVI and 52% for M-VAC (P = 0.3). There was a statistically significant difference in median disease-related survival time favouring M-VAC (16 months; range, 6 to 22+) versus M-CAVI (9 months; range, 6 to 14+) (P = 0.03).r
An audit of 381 elderly patients with advanced TCC of the bladder showed the elderly tolerate cisplatin-based therapy and gain as much benefit as their younger counterparts. Survival correlated with performance status and haemoglobin level but not with age.r Additionally, the advent of novel anti-emetics such as aprepitant makes cisplatin easier to use in this population.
These data indicate that carboplatin and gemcitabine may be an alternative to cisplatin-based regimen for the treatment of advanced urothelial cancer, particularly in those with poor performance status. However, in the absence of randomised studies, carboplatin should not be substituted for cisplatin in these regimens as a general rule. Carboplatin and gemcitabine should not be used in the adjuvant setting.
Efficacy
Overall Survival (n=41) r:

© Cancer 2003
Toxicity
Toxicityr |
Grade 1 to 2 (%) |
Grade 3 to 4 (%) |
Leucopenia |
49 |
44 |
Neutropenia |
31 |
63 |
Thrombocytopenia |
24 |
32 |
Anaemia |
39 |
63 |
Vomiting |
24 |
7 |
Serum Creatinine |
47 |
2 |
Alopecia |
31 |
0 |
Oedema |
10 |
7 |
Peripheral Neuropathy |
5 |
2 |
Asthenia |
54 |
19 |
Infection |
34 |
5 |
Hepatic |
36 |
0 |
© Cancer 2003