The ICON3r study concluded that a combination of paclitaxel and carboplatin was not superior to either CAP (cyclophosphamide, doxorubicin, cisplatin) or single-agent carboplatin as a first-line treatment for women requiring chemotherapy for ovarian cancer. The evidence showed that paclitaxel plus carboplatin is more toxic than carboplatin alone, in particular causing more alopecia, fever and sensory neuropathy. It was concluded that, if a difference existed between the treatment arms, it was very small.
Despite the findings of ICON3r, most centres still consider carboplatin and paclitaxel the treatment of choice for good performance status patients. One reason for this clinical decision is that ICON3r contradicts previous studies, such as GOG 111, which demonstrated that combination treatment was superior to single agent carboplatin.
The favourable toxicity profile of single-agent carboplatin and the efficacy data from ICON3r support the decision to use single agent treatment in patients in whom the addition of paclitaxel is inappropriate (elderly, patient preference or paclitaxel contraindicated).
Efficacy
ICON2 r
Equivalence of anthracycline containing combination CAP and single-agent carboplatin. Median survival 33 months for both groups (p=0.98)
ICON3 r
Absolute difference in 2 year survival of 0.6% (95% CI : 62.0% - 62.6%) in favour of paclitaxel plus carboplatin, compared with both controls. Median survival, difference of 0.7 months with a median survival of 35.4 months in the control group and 36.1 months in the paclitaxel plus carboplatin group (p=0.16)
Absolute difference in 1 year progression-free survival of 2.2% in favour of paclitaxel plus carboplatin, from 59% to 61.2%, compared with either control. These results translate into a median progression-free survival of 16.1 months for the control groups and 17.3 months for the paclitaxel plus carboplatin group.
Progression-free survival with carboplatin control armr
© Lancet 2002
Toxicity
Moderate or severe toxic effects seen during treatment (grade 3 to 4 except where stated)
Toxicityr |
Carboplatin (control)
% |
Paclitaxel plus
carboplatin
% |
CAP (control)
% |
Paclitaxel plus
carboplatin
% |
Alopecia |
4 |
73 |
76 |
80 |
Nausea and vomiting |
9 |
9 |
23 |
10 |
Haematological* |
32 |
25 |
23 |
29 |
Fever requiring antibiotics* |
3 |
10 |
23 |
13 |
Sensory neuropathy
(grade 2 to 3) |
1 |
19 |
3 |
18 |
Motor neuropathy* |
< 1 |
3 |
1 |
1 |
Other** |
4 |
7 |
6 |
6 |
* These data were collected by the non-Italian centres only
** Including ototoxicity, renal toxicity, cardiac toxicity and stomatitis
© Lancet 2002