This protocol has been superseded due to the availability of superior alternatives.
The randomised phase III trial by Tan comparing gemcitabine/vinorelbine with carboplatin/vinorelbine (316 patients) reported overall response rate for carboplatin/vinorelbine of 20.8%, PFS 3.9 months and median survival 8.6 months.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
Carboplatin/vinorelbine was compared with gemcitabine/vinorelbine in a randomised phase III trial by Tan et al. Response rates for the gemcitabine/vinorelbine arm were 28% (not statistically significant) and a median survival of 11.5 months (p= 0.01). The authors concluded that gemcitabine/vinorelbine compared to carboplatin/vinorelbine resulted in a similar overall response rate, favourable median survival and a better toxicity profile.r
Tanr |
Vinorelbine Gemcitabine |
Vinorelbine Carboplatin |
p-value |
Response rate |
28% |
20.8% |
0.15 |
Time to progression |
4.4 months |
3.9 months |
0.18 |
Median survival |
11.5 months |
8.6 months |
0.01 |
1 year survival |
48.9% |
32.4% |
|
Toxicity
Tan et al, (2005) reported that tolerance was better in the gemcitabine/vinorelbine arm as compared to the carboplatin/vinorelbine patients. Four toxic deaths were recorded in the carboplatin/vinorelbine group. Clinical benefit response rate was 32.4% compared to 40.9% in 111 and 110 evaluable patients in carboplatin/vinorelbine and gemcitabine/vinorelbine, respectively. CONCLUSION: gemcitabine/vinorelbine compared to carboplatin/vinorelbine resulted in a similar overall response rate, favourable median survival and a better toxicity profile. For non-cisplatin-based chemotherapy, gemcitabine/vinorelbine is a useful alternative.r
Toxicity Grade 3 or 4r |
Carboplatin/vinorelbine (%) |
Gemcitabine/vinorelbine (%) |
Neutropenia |
45 |
23 |
Infection |
9 |
3 |
Anaemia |
21 |
5 |
Thrombocytopenia |
5 |
1 |
Nausea/Vomiting |
4 |
2 |
Asthenia |
11 |
4 |
Constipation |
4 |
2 |
Venous irritation |
1 |
3 |
Horvath et al, (2001) reported that the main toxicity of carboplatin/vinorelbine was myelopsuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.r
Adverse eventr |
Grade 3 episodes (%) |
Grade 4 episodes (%) |
Neutropenia |
20 |
24 |
Anaemia |
5 |
0 |
Thrombocytopenia |
1 |
0 |
Sepsis |
0 |
1 |
Autonomic neuropathy |
0 |
1 |