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 Tattersall & 5 others Stefano Greggi, Parker Vicky, Mahesh K B Parmar, Lesley A. Stewart, Jayne F. Tierney

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

Fingerprint

Uterine Cervical Neoplasms
Drug Therapy
Radiotherapy
Cisplatin
Survival
Risk Reduction Behavior
Patient Selection
Neoplasms
Therapeutics

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., ... 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

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

In: The Cochrane database of systematic reviews, No. 4, CD001774, 2009.

Research output: Contribution to journalArticle

Tierney, J, Benedetti-Panici, P, Bermudez, A, Blake, P, Cárdenas, J, Chang, TC, 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, Tattersall, M, Greggi, S, Vicky, P, Parmar, MKB, Stewart, LA & Tierney, JF 2009, 'Neoadjuvant chemotherapy for locally advanced cervix cancer', The Cochrane database of systematic reviews, no. 4, CD001774. https://doi.org/10.1002/14651858.CD001774.pub2
Tierney J, Benedetti-Panici P, Bermudez A, Blake P, Cárdenas J, Chang TC et al. Neoadjuvant chemotherapy for locally advanced cervix cancer. The Cochrane database of systematic reviews. 2009;(4). CD001774. https://doi.org/10.1002/14651858.CD001774.pub2
Tierney, Jayne ; Benedetti-Panici, Pierluigi ; Bermudez, Adriana ; Blake, Peter ; Cárdenas, Jesus ; Chang, Ting Chang ; Chiara, Silvana ; Di Paola, G. ; Floquet, Anne ; Guthrie, David ; Kigawa, Junzo ; Kumar, Lalit ; Leborgne, Felix ; Lodge, Nick ; Poole, Chris ; Sardi, Juan ; Souhami, Luis ; Sundfør, Kolbein ; Symonds, Paul ; Tattersall, Martin ; Greggi, Stefano ; Vicky, Parker ; Parmar, Mahesh K B ; Stewart, Lesley A. ; Tierney, Jayne F. / Neoadjuvant chemotherapy for locally advanced cervix cancer. In: The Cochrane database of systematic reviews. 2009 ; No. 4.
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doi = "10.1002/14651858.CD001774.pub2",
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TY - JOUR

T1 - Neoadjuvant chemotherapy for locally advanced cervix cancer

AU - Tierney, Jayne

AU - Benedetti-Panici, Pierluigi

AU - Bermudez, Adriana

AU - Blake, Peter

AU - Cárdenas, Jesus

AU - Chang, Ting Chang

AU - Chiara, Silvana

AU - Di Paola, G.

AU - Floquet, Anne

AU - Guthrie, David

AU - Kigawa, Junzo

AU - Kumar, Lalit

AU - Leborgne, Felix

AU - Lodge, Nick

AU - Poole, Chris

AU - Sardi, Juan

AU - Souhami, Luis

AU - Sundfør, Kolbein

AU - Symonds, Paul

AU - Tattersall, Martin

AU - Greggi, Stefano

AU - Vicky, Parker

AU - Parmar, Mahesh K B

AU - Stewart, Lesley A.

AU - Tierney, Jayne F.

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

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KW - Antineoplastic agents [therapeutic use]

KW - Chemotherapy

KW - Cisplatin [therapeutic use]

KW - Female

KW - Humans

KW - Neoadjuvant therapy

KW - Randomized controlled trials as topic

KW - Survival analysis

KW - Uterine cervical neoplasms [drug therapy; pathology]

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