Surgery, radiotherapy or sometimes both were the best treatments for locally advanced cervical cancer. This is cancer that has spread beyond the cervix (neck of the womb) into the surrounding tissues, such as the vagina, sides of the pelvis or nearby lymph nodes. The exact choice of treatment would have depended on the size and location of the tumour and the preferences of the woman and her doctor.
Nowadays, women with this type of cancer may be given combined chemotherapy (drug treatment) and radiotherapy (x-rays that kill cancer cells) at the same time. Or, they may have surgery (to remove the womb) as well as this combined chemotherapy and radiotherapy. However, giving chemotherapy before these treatments (neoadjuvant chemotherapy) might have a similar benefit, but have less side effects than giving the treatments at the same time.
This review aimed to assess the benefits and risks of giving chemotherapy before surgery, before radiotherapy or before both treatments.
Our first comparison was based on 18 trials and 2074 women. The women who were given chemotherapy either more than a fortnight apart or with a less intense dose of cisplatin before their radiotherapy, did not live as long as those who were only given radiotherapy. However, women given chemotherapy either less than a fortnight apart or with a more intense dose of cisplatin before their radiotherapy, seemed to live longer than those who were only given radiotherapy. These second results are based on less data and are not so convincing. There were very few serious side effects that continued long after treatment and they seemed to be similar whether chemotherapy was given or not.
Our second comparison was based on 5 trials and 872 women. The women who were given chemotherapy before surgery seemed to live longer than those who were only given radiotherapy. However, there was a small amount of data, there were differences between results of trials and other treatments were used. Therefore, it is not clear if the benefit might be for reasons other than the chemotherapy.
Further assessment of neoadjuvant chemotherapy in randomised trials is required. It may be valuable to compare it to a combined chemotherapy and radiotherapy approach or even to use neoadjuvant chemotherapy together with combined chemotherapy and radiotherapy.
The timing and dose intensity of cisplatin-based neoadjuvant chemotherapy appears to have an important impact on whether or not it benefits women with locally advanced cervical cancer and warrants further exploration. Obtaining additional IPD may improve the strength of these conclusions.
The impact of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer remains uncertain.
This review of individual patient data (IPD) aimed to assess the effect of;
Neoadjuvant chemotherapy followed by radical radiotherapy compared to the same radiotherapy; and
Neoadjuvant chemotherapy followed by surgery compared to radical radiotherapy.
Searches of Medline, CancerLit and trial registers were supplemented by hand-searching conference proceedings and contacting relevant trialists. Searches have been updated to February 2006.
Trials had to be properly randomised and include patients with locally advanced cervical cancer who had received neoadjuvant chemotherapy either before radiotherapy or surgery (or both).
We collected, validated and re-analysed updated trial data on all randomised patients from all relevant trials. The person responsible for the trial resolved queries and verified the final data. Treatment comparisons 1 and 2 were analysed separately. For all outcomes, we obtained overall hazard ratios using the fixed-effect model. We pre-specified analyses that grouped trials by important aspects of their design and patients by their or their tumour characteristics, to assess whether they might influence the effect of neoadjuvant chemotherapy.
We obtained data from 18 trials and 2074 patients for the first comparison. Considering these trials together there was a high level of statistical heterogeneity, a substantial amount of which was explained by analyses of trial groups. Trials using chemotherapy cycle lengths shorter than 14 days (HR = 0.83, 95% CI = 0.69 to 1.00, p = 0.046) or cisplatin dose intensities greater than 25 mg/m2 per week (HR = 0.91, 95% CI = 0.78 to 1.05, p = 0.20) tended to show an advantage of neoadjuvant chemotherapy on survival. In contrast, trials using cycle lengths longer than 14 days (HR = 1.25, 95% CI = 1.07 to 1.46, p = 0.005) or cisplatin dose intensities lower than 25 mg/m2 per week (HR = 1.35, 95% CI = 1.11 to 1.14, p = 0.002) showed a detrimental effect of neoadjuvant chemotherapy on survival. In the second comparison, data from 5 trials and 872 patients were obtained. The combined results (HR = 0.65, 95% CI = 0.53 to 0.80, p = 0.0004) indicated a highly significant reduction in the risk of death with neoadjuvant chemotherapy, but with heterogeneity in both the design and results.