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Meta-Analysis
. 2005 Jul 20;2005(3):CD002225.
doi: 10.1002/14651858.CD002225.pub2.

Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix

J Green  1 , J Kirwan, J Tierney, C Vale, P Symonds, L Fresco, C Williams, M Collingwood
Affiliations
Meta-Analysis

Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix

J Green et al. Cochrane Database Syst Rev. .

Abstract

Background: The National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials (RCTs).

Objectives: To review all known RCTs comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer.

Search strategy: We searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched.

Selection criteria: This review includes RCTs in cervical cancer comparing concomitant chemoradiation with radiotherapy in the experimental arm. Trials allowing further adjuvant chemotherapy or hydroxyurea were included. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded.

Data collection and analysis: Two authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. Few trials reported acute toxicity adequately, but where possible ORs were calculated for the main types and severities of acute toxicity. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Late toxicity was rarely described in sufficient detail so could only be reviewed qualitatively.

Main results: The original review was based on nineteen trials (17 published and two unpublished) including 4580 patients. This update includes twenty four trials (21 published, 3 unpublished) and 4921 patients, although due to patient exclusion and differential reporting 61% to 75% were available for the analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether or not platinum was used with absolute benefits of 10% and 13% respectively. There was, however, statistical heterogeneity for these outcomes. There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for local recurrence and a suggestion of a benefit for distant recurrence. Acute haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Late effects of treatment were not well reported and so the impact of chemoradiation on these effects could not be determined adequately. Treatment-related deaths were rare.

Authors' conclusions: Concomitant chemoradiation appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also appears to reduce local and distant recurrence suggesting concomitant chemotherapy may afford radiosensitisation and systemic cytotoxic effects. Some acute toxicity is increased, but the long-term side effects are still not clear.

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Conflict of interest statement

None known

Figures

1.1
1.1. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 1 Survival by type of chemotherapy.
1.2
1.2. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 2 Survival by scheduling of chemotherapy.
1.3
1.3. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 3 Survival by hydroxyurea on control.
1.4
1.4. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 4 Survival by timing of chemotherapy.
1.5
1.5. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 5 Survival by stage.
1.6
1.6. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 6 Progression‐free survival by type of chemotherapy.
1.7
1.7. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 7 Rate of local recurrence by type of chemotherapy.
1.8
1.8. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 8 Rate of distant recurrence by type of chemotherapy.
1.9
1.9. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 9 Rate of distant +/‐ local recurrence by type of chemotherapy.
1.10
1.10. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 10 Acute haematological toxicity (non‐specified).
1.11
1.11. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 11 Acute white blood cell toxicity.
1.12
1.12. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 12 Acute haemoglobin toxicity.
1.13
1.13. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 13 Acute platelet toxicity.
1.14
1.14. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 14 Acute GI toxicity.
1.15
1.15. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 15 Acute nausea / vomiting.
1.16
1.16. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 16 Acute GU toxicity.
1.17
1.17. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 17 Acute skin toxicity.
1.18
1.18. Analysis
Comparison 1 Concomitant chemoradiotherapy versus radiotherapy, Outcome 18 Acute neurologic toxicity.
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