Neoadjuvant chemotherapy for locally advanced cervix cancer

Jayne Tierney, Pierluigi Benedetti-Panici, Adriana Bermudez, Peter Blake, Jesus Cárdenas, Ting Chang Chang, Silvana Chiara, G. Di Paola, Anne Floquet, David Guthrie, Junzo Kigawa, Lalit Kumar, Felix Leborgne, Nick Lodge, Chris Poole, Juan Sardi, Luis Souhami, Kolbein Sundfør, Paul Symonds, Martin TattersallStefano Greggi, Parker Vicky, Mahesh K B Parmar, Lesley A. Stewart, Jayne F. Tierney

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Abstract

Background: The impact of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer remains uncertain. Objectives: 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. Search strategy: Searches of Medline, Cancer Lit and trial registers were supplemented by hand-searching conference proceedings and contacting relevant trialists. Searches have been updated to February 2006. Selection criteria: 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). Data collection and analysis: 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. Main results: 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. Authors' conclusions: 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.

Original languageEnglish
Article numberCD001774
JournalThe Cochrane database of systematic reviews
Issue number4
DOIs
Publication statusPublished - 2009

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Keywords

  • Adjuvant
  • Antineoplastic agents [therapeutic use]
  • Chemotherapy
  • Cisplatin [therapeutic use]
  • Female
  • Humans
  • Neoadjuvant therapy
  • Randomized controlled trials as topic
  • Survival analysis
  • Uterine cervical neoplasms [*drug therapy; pathology]

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology (medical)

Cite this

Tierney, J., Benedetti-Panici, P., Bermudez, A., Blake, P., Cárdenas, J., Chang, T. C., Chiara, S., Di Paola, G., Floquet, A., Guthrie, D., Kigawa, J., Kumar, L., Leborgne, F., Lodge, N., Poole, C., Sardi, J., Souhami, L., Sundfør, K., Symonds, P., ... Tierney, J. F. (2009). Neoadjuvant chemotherapy for locally advanced cervix cancer. The Cochrane database of systematic reviews, (4), [CD001774]. https://doi.org/10.1002/14651858.CD001774.pub2