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Meta-Analysis
. 2012 Jun 13;6(6):CD005342.
doi: 10.1002/14651858.CD005342.pub3.

Adjuvant platinum-based chemotherapy for early stage cervical cancer

Daniela D Rosa  1 , Lídia R F Medeiros, Maria I Edelweiss, Paula R Pohlmann, Airton T Stein
Affiliations
Meta-Analysis

Adjuvant platinum-based chemotherapy for early stage cervical cancer

Daniela D Rosa et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: This is an updated version of the original Cochrane review published in The Cochrane Library 2009, Issue 3. Most women with early cervical cancer (stages I to IIA) are cured with surgery or radiotherapy, or both. We performed this review originally because it was unclear whether cisplatin-based chemotherapy after surgery, radiotherapy or both, in women with early stage disease with risk factors for recurrence, was associated with additional survival benefits or risks.

Objectives: To evaluate the effectiveness and safety of platinum-based chemotherapy after radical hysterectomy, radiotherapy, or both in the treatment of early stage cervical cancer.

Search methods: For the original 2009 review, we searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, LILACS, BIOLOGICAL ABSTRACTS and CancerLit, the National Research Register and Clinical Trials register, with no language restriction. We handsearched abstracts of scientific meetings and other relevant publications. We extended the database searches to November 2011 for this update.

Selection criteria: Randomised controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy (after radical surgery, radiotherapy or both) with no adjuvant chemotherapy, in women with early stage cervical cancer (stage IA2-IIA) with at least one risk factor for recurrence.

Data collection and analysis: Two review authors extracted data independently. Meta-analysis was performed using a random-effects model, with death and disease progression as outcomes.

Main results: For this updated version, we identified three additional ongoing trials but no new studies for inclusion. Three trials including 368 evaluable women with early cervical cancer were included in the meta-analyses. The median follow-up period in these trials ranged from 29 to 42 months. All women had undergone surgery first. Two trials compared chemotherapy combined with radiotherapy to radiotherapy alone; and one trial compared chemotherapy followed by radiotherapy to radiotherapy alone. It was not possible to perform subgroup analyses by stage or tumour size.Compared with adjuvant radiotherapy, chemotherapy combined with radiotherapy significantly reduced the risk of death (two trials, 297 women; hazard ratio (HR) = 0.56, 95% confidence interval (CI): 0.36 to 0.87) and disease progression (two trials, 297 women; HR = 0.47, 95% CI 0.30 to 0.74), with no heterogeneity between trials (I² = 0% for both meta-analyses). Acute grade 4 toxicity occurred significantly more frequently in the chemotherapy plus radiotherapy group than in the radiotherapy group (risk ratio (RR) 5.66, 95% CI 2.14 to 14.98). We considered this evidence to be of a moderate quality due to small numbers and limited follow-up in the included studies. In addition, it was not possible to separate data for bulky early stage disease.In the one small trial that compared adjuvant chemotherapy followed by radiotherapy with adjuvant radiotherapy alone there was no significant difference in disease recurrence between the groups (HR = 1.34; 95% CI 0.24 to 7.66) and OS was not reported. We considered this evidence to be of a low quality.No trials compared adjuvant platinum-based chemotherapy with no adjuvant chemotherapy after surgery for early cervical cancer with risk factors for recurrence.

Authors' conclusions: The addition of platinum-based chemotherapy to adjuvant radiotherapy (chemoradiation) may improve survival in women with early stage cervical cancer (IA2-IIA) and risk factors for recurrence. Adjuvant chemoradiation is associated with an increased risk of severe acute toxicity, although it is not clear whether this toxicity is significant in the long-term due to a lack of long-term data. This evidence is limited by the small numbers and poor methodological quality of included studies. We await the results of three ongoing trials, that are likely to have an important impact on our confidence in this evidence.

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Figures

Figure 1
Figure 1
Methodological quality graph: review authors’ judgements about each methodological quality item presented as percentages across all included studies.
Figure 2
Figure 2
Methodological quality summary: review authors’ judgements about each methodological quality item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

    1. *

    2. Peters WA, 3rd, Liu PY, Barrett RJ, 2nd, Stock RJ, Monk BJ, Berek JS, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. Journal of Clinical Oncology. 2000;18(8):1606–13. - PubMed

    1. *

    2. Cancer Research UK A prospective randomised trial of adjuvant chemotherapy in node positive early stage carcinoma of the cervix - Protocol CE3005. UK Clinical Trials Register. 2001.

    1. *

    2. Tattersall MH, Ramirez C, Coppleson M. A randomized trial of adjuvant chemotherapy after radical hysterectomy in stage Ib-IIa cervical cancer patients with pelvic lymph node metastases. Gynecologic Oncology. 1992;46(2):176–81. - PubMed

References to studies excluded from this review

    1. Argenta PA, Ghebre R, Dusenbery KE, Chen MD, Judson PL, Downs LS, et al. Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. European Journal of Gynaecological Oncology. 2006;27(3):231–5. - PubMed
    1. Blohmer JU, Paepke S, Bohmer D, Ernhardt B, Sehouli J, Elling D, et al. Adjuvant chemotherapy of cervix carcinoma--results of a phase II study. Zentralblatt fur Gynakologie. 2001;123(5):286–91. - PubMed
    1. Buxton EJ, Saunders N, Blackledge GR, Kelly K, Redman CW, Monaghan J, et al. The potential for adjuvant therapy in early-stage cervical cancer. Cancer Chemotherapy and Pharmacology. 1990;26(suppl 26):S17–21. - PubMed
    1. Curtin JP, Hoskins WJ, Venkatraman ES, Almadrones L, Podratz KC, Long H, et al. Adjuvant chemotherapy versus chemotherapy plus pelvic irradiation for high-risk cervical cancer patients after radical hysterectomy and pelvic lymphadenectomy (RH-PLND): a randomized phase III trial. Gynecologic Oncology. 1996;61:3–10. - PubMed
    1. Dimpfl T, Stumpfe M, Baltzer J, Genz T. Results of adjuvant chemotherapy of operated high risk cervix carcinoma. Geburtshilfe Frauenheilkd. 1996;56(10):517–9. - PubMed

References to ongoing studies

    1. Ryu SY, Koh W. Radiation therapy with or without chemotherapy in patients with stage I or stage II cervical cancer who previously underwent surgery. www.ClinicalTrials.gov. NCT01101451.
    1. Hong J-H. Cisplatin based chemoradiation v.s radiotherapy for cervical cancer and with clinically defined good prognosis. www.ClinicalTrials.gov. NCT00846508.
    1. Liu J, Huang H. A multicenter trial of benefits of adding post-surgery chemotherapy for cervical cancer. www.ClinicalTrials.gov. NCT00806117.

Additional references

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    1. Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration (CCCMAC) Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: individual patient data meta-analysis. Cochrane Database of Systematic Reviews. 2010;(Issue 1) [DOI: 10.1002/ 14651858.CD008285] - PMC - PubMed
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References to other published versions of this review

    1. Rosa DD, Medeiros LRF, Edelweiss EI, Bozzetti MC, Pohlmann PR, Stein AT. Adjuvant platinum-based chemotherapy for early stage cervical cancer. Cochrane Database of Systematic Reviews. 2009;(Issue 3) [DOI: 10.1002/14651858.CD005342.pub2] - PubMed

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