Carboplatin and paclitaxel is a widely studied reference regimen for NSCLC.
A number of generalisations can be made.
- Carboplatin-paclitaxel is equally effective as a number of other reference regimens.r Choice of regimens is guided by toxicity, cost and convenience.
- Carboplatin and paclitaxel is more effective than single agent paclitaxel.r
- Cisplatin adds a small survival advantage over carboplatin paclitaxel but this needs to be balanced against the additional toxicity and inconvenience.r
On this basis, carboplatin and paclitaxel is a commonly used regimen in ECOG 0 to 2 patients.
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
Response rates in response-evaluable patients with measurable tumourr
Rosell et alr |
Paclitaxel/Cisplatin
n=284 (%)
|
Paclitaxel/Carboplatin
n=279 (%) |
Complete response |
1 |
1 |
Partial response |
28 |
25 |
Stable disease |
43 |
40 |
Progressive disease |
20 |
29 |
Early death toxicity |
8 |
6 |
Rosell et alr reported that the response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively.r
Schiller et al rcompared carboplatin/paclitaxel with 3 other regimens and the response rates are summarised below. It was concluded that third generation chemotherapy regimens in patients with NSCLC who have a good performance status can moderately improve survival at one and two years. No significant difference in survival was observed among four commonly used regimens.r
Variable |
Cisplatin/
Paclitaxel
n=288
(%)
|
Cisplatin/
Gemcitabine
n=288
(%) |
Cisplatin/
Docetaxel
n=289
(%) |
Carboplatin/
Paclitaxel
n=290
(%) |
Total
n=1155 |
Complete response |
<1 |
1 |
<1 |
<1 |
<1 |
Partial response |
21 |
21 |
17 |
16 |
19 |
Stable disease |
18 |
18 |
25 |
23 |
21 |
Progressive disease |
49 |
40 |
42 |
49 |
45 |
Could not determine |
13 |
20 |
16 |
11 |
15 |
Overall response |
21 |
22 |
17 |
17 |
19 |
Median survival months |
7.8 |
8.1 |
7.4 |
8.1 |
7.9 |
1 year 95% (CI) |
31 |
36 |
31 |
34 |
33 |
2 year 95% (CI) |
10 |
13 |
11 |
11 |
11 |
Median time to progression 95%(CI) |
3.4 |
4.2 |
3.7 |
3.1 |
3.6 |
Toxicity
In the Rosell et al. (2002) study, excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms.r
The following table summarises toxic complications in the Schiller et al. (2002) study. It was concluded that the regimen of carboplatin/paclitaxel had a lower rate of toxic effects than the other regimens and, on the basis of these results, ECOG has chosen this regimen as its reference for future studies.
Toxicitiesr
© New Engl J Med 2002