Adjuvant platinum-based chemotherapy for early stage cervical cancer.
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.


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


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.


METHODS
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.


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


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.


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.
OncologyUnit,HospitalMoinhos deVento, PortoAlegre,Brazil. dornellesrosa@hotmail.com
Daniela D
DD
Rosa
Lídia R F
LR
Medeiros
Maria I
MI
Edelweiss
Paula R
PR
Pohlmann
Airton T
AT
Stein
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007044:Hysterectomy; D009367:Neoplasm Staging; D017671:Platinum Compounds / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery
D017671:Platinum Compounds; D002945:Cisplatin; D005472:Fluorouracil