This protocol has been superseded due to the availability of superior alternatives.
Two large phase III studies comparing cisplatin/vinorelbine with other platin-based doublet regimens in chemotherapy-naïve advanced NSCLC have been published.
The first Scagliotti, compared cisplatin/vinorelbine (cis 100 mg/m2 D1, vinorelbine 25 mg/m2 q1/52) with cisplatin/gemcitabine and carboplatin/paclitaxel. Six hundred twelve patients were entered on study. For cisplatin / vinorelbine, overall response rate was 30%, with a median time to progression of 4.6 months and median survival of 9.5 months. There was no statistical difference for these outcomes for the three regimens. Cisplatin/vinorelbine was associated with a greater incidence of grade 3/4 neutropenia, and nausea and vomiting.r
The second study by Fossella randomised 1218 patients to either cisplatin/vinorelbine, or docetaxel with either cisplatin or carboplatin. Overall response rate for cisplatin/vinorelbine was 24.5%, with a median survival of 10.1 months. These results were inferior to cisplatin/docetaxel (31.6%, 11.3 months) and equivalent to carboplatin/docetaxel. Neutropenia, febrile neutropenia and thrombocytopenia rates were similar for the three arms, but there was a higher incidence of anaemia with cisplatin/vinorelbine.r
A phase III study by Georgoulias compared cisplatin/vinorelbine with a non-platin doublet regimen, and showed similar overall survival (9.7 months for cisplatin/vinorelbine) and a non-significant trend for improved response rate in favour of cisplatin/vinorelbine (39.2%). The docetaxel/gemcitabine regimen was associated with less marrow-related toxicity and less nausea and vomiting.r
Cisplatin vs. Carboplatin
A meta-analysis of abstracted data by Hotta et alr compared the results of 9 trials involving 2698 patients between cisplatin based combination chemotherapy (1489 patients) against carboplatin based chemotherapy (1479 patients) in first line treatment of advanced NSCLC. It showed that cisplatin based chemotherapy achieved higher objective response rates (OR 1.36, P<0.01) but showed no overall survival advantage (HR 1.05, P=.515). Toxicity was not uniformly comparable but there were no significant differences in treatment related deaths.
Optimal chemotherapy doublet
The predictive influence of histological subtypes on outcomes has been shown in recent studies. In a combined analysis of individual patient data from three phase III trials in first line treatment of NSCLC, Treat et alr demonstrated a difference in overall survival between patients with non-squamous and squamous histology to different chemotherapy combinations. In patients with non-squamous histology, pemetrexed/cisplatin conferred superior median overall survival (11 months) compared with other regimens including gemcitabine/carboplatin (8.3 months). However, in patients with squamous histology, vinorelbine/cisplatin conferred the best median overall survival outcome and gemcitabine/cisplatin was superior to pemetrexed/ cisplatin.
Efficacy
Approximately 60% of patients in each group had stage lV disease.
Patients treated with docetaxel carboplatin or docetaxel cisplatin reported consistently improved global QoL compared with patients on vinorelbine cisplatin.
The one year survival was x 46% (HR=1.183; p= 0.44) and the 2 year survival was 21% (HR=1.183; p= 0.44)
Fossellar |
Docetaxel Cisplatin |
Vinorelbine Cisplatin |
p-value |
Response rate |
32% |
25% |
0.29 |
Time to progression |
22 weeks |
23 weeks |
0.805 |
Overall median survival |
11.3 months |
10.1 months |
0.44 |
TAX 326r |
Docetaxel
cisplatin n=408 (%)
|
Docetaxel carboplatin n=406 (%) |
Vinorelbine
cisplatin n=404 (%) |
Overall response |
32 |
24 |
25 |
95% CI |
27 to 36 |
20 to 28 |
20 to 29 |
Complete response |
2 |
1 |
2 |
Partial response |
30 |
23 |
23 |
No change or stable disease |
43 |
46 |
42 |
Progressive disease |
18 |
22 |
21 |
Not assessable |
8 |
8 |
12 |
In the planned pair-wise comparison between docetaxel/carboplatin (Dcb) versus vinorelbine/cisplatin (VC), the overall median survival was similar, 9.4 months and 9.9 months respectively. One and 2-year survival rates for Dcb versus VC were 38%v40%, and 18% v 14% respectively
Survival:r
© J Clin Oncol 2003
Toxicity
More patients on the vinorelbine cisplatin arm (22.5%) discontinued treatment because of adverse events compared with those on the docetaxel carboplatin (9.1%) and docetaxel cisplatin (15.7%).
Neutropenia, febrile neutropenia and thrombocytopenia were similar for all three arms, but there was a higher incidence of anaemia with cisplatin/navelbine arm.
There were no treatment related deaths reported.
Grade 3 and 4 Toxicities from TAX 326 study group. Note: doses were higher in this study.r
Adverse eventr |
Vinorelbine Cisplatin
n=396 (%) |
Docetaxel Cisplatin
n=406 (%) |
Docetaxel Carboplatin n=401 (%) |
Leucopenia |
55 |
43 |
50 |
Neutropenia |
79 |
75 |
74 |
Thrombocytopenia |
4 |
3 |
7 |
Anaemia |
24 |
7 |
11 |
Infection |
8 |
8 |
11 |
Asthenia |
14 |
12 |
11 |
Nausea |
16 |
10 |
6 |
Pulmonary |
11 |
10 |
14 |
Pain |
8 |
8 |
9 |
Vomiting |
16 |
8 |
4 |
Diarrhoea |
3 |
7 |
5 |
Anorexia |
5 |
5 |
3 |