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Review
. 2014 May 15;2014(5):CD010681.
doi: 10.1002/14651858.CD010681.pub2.

Adjuvant Chemotherapy for Advanced Endometrial Cancer

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Free PMC article
Review

Adjuvant Chemotherapy for Advanced Endometrial Cancer

Khadra Galaal et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective.

Objectives: To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV).

Search methods: We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials.

Selection criteria: Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer.

Data collection and analysis: Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software.

Main results: We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data.Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison.

Authors' conclusions: There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regimens in the long-term. Further research is needed to determine which chemotherapy regimen(s) are the most effective and least toxic, and whether the addition of radiotherapy further improves outcomes. A large trial evaluating the benefits and risks of adjuvant chemoradiation versus chemotherapy in advanced endometrial cancer is ongoing.

Conflict of interest statement

None

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.
2
2
Study flow diagram.
3
3
Forest plot of comparison: 1 Chemotherapy vs radiotherapy, outcome: 1.1 OS (Stage III/IV).
4
4
Forest plot of comparison: 1 Chemotherapy versus radiotherapy, outcome: 1.6 PFS (Stage III/IV).
1.1
1.1. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 1 OS (Stage III/IV).
1.2
1.2. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 2 OS (stage III/IV) (unadjusted data).
1.3
1.3. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 3 OS (stage III/IV dichotomous).
1.4
1.4. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 4 OS (Stage III only).
1.5
1.5. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 5 OS (Stage III dichotomous).
1.6
1.6. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 6 PFS (Stage III/IV).
1.7
1.7. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 7 PFS (stage III/IV dichotomous).
1.8
1.8. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 8 PFS (Stage III only).
1.9
1.9. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 9 PFS (Stage III dichotomous).
1.10
1.10. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 10 Severe adverse events (G3/4).
1.11
1.11. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 11 Treatment discontinuation due to toxicity.
1.12
1.12. Analysis
Comparison 1 Chemotherapy vs radiotherapy, Outcome 12 Treatment‐related deaths.
2.1
2.1. Analysis
Comparison 2 CDP vs CD, Outcome 1 OS (stage III/IV).
2.2
2.2. Analysis
Comparison 2 CDP vs CD, Outcome 2 PFS (stage III/IV).
2.3
2.3. Analysis
Comparison 2 CDP vs CD, Outcome 3 Severe adverse events (G3/4).
2.4
2.4. Analysis
Comparison 2 CDP vs CD, Outcome 4 Treatment discontinuation.

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  • Cochrane Database Syst Rev. doi: 10.1002/14651858.CD010681

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