Adjuvant chemotherapy after concurrent chemoradiation for locally advanced
cervical cancer.
Author(s): Tangjitgamol S(1), Katanyoo K, Laopaiboon M, Lumbiganon P, Manusirivithaya S,
Supawattanabodee B.
Affiliation(s): Author information:
(1)Department of Obstetrics and Gynaecology, Faculty of Medicine Vajira Hospital,
Navamindradhiraj University, 681 Samsen Road, Dusit District, Bangkok, 10300,
Thailand. siriwanonco@yahoo.com.
Publication date & source: 2014, Cochrane Database Syst Rev. , 12:CD010401
BACKGROUND: Current standard treatment for patients with cervical cancer who have
locally advanced stage disease (International Federation of Gynecology and
Obstetrics (FIGO) stage IIB to IVA) is concurrent chemoradiation therapy (CCRT).
However, less than two-thirds of patients in this group survive for longer than
five years post treatment. Adjuvant chemotherapy (ACT) can be given in an attempt
to improve survival by eradicating residual disease in the pelvis and treating
occult disease outside the pelvic radiation field. However, inconsistency in
trial design, inclusion criteria for participants, interventions and survival
benefit has been noted among trials of ACT after CCRT for locally advanced
cervical cancer (LACC).
OBJECTIVES: To evaluate the effect of adjuvant chemotherapy (ACT) after
concurrent chemoradiation (CCRT) on survival of women with locally advanced
cervical cancer compared with CCRT alone.
SEARCH METHODS: We searched the Cochrane Gynaecological Review Group Trial
Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
EMBASE and conference proceedings to March 2014. We handsearched citation lists
of relevant studies.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing CCRT alone
versus CCRT plus ACT were included. Patients were diagnosed with cervical cancer
FIGO stage IIB to IVA with a histopathology of squamous cell carcinoma,
adenosquamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma.
DATA COLLECTION AND ANALYSIS: Two review authors (ST, KK) selected relevant
trials, extracted data, assessed risk of bias independently, compared results and
resolved disagreements by discussion.
MAIN RESULTS: We identified two RCTs involving 978 women with cervical cancer
stage IIB to IVA. As the trials were significantly different clinically, we did
not perform meta-analyses. One industry-funded trial involving 515 women compared
CCRT (cisplatin) versus CCRT (cisplatin and gemcitabine) plus ACT (two additional
cycles). This trial reported significant improvement in progression-free survival
(PFS) and overall survival (OS) in women who were given CCRT plus ACT compared
with those treated with CCRT alone: Three-year PFS was 74.4% versus 65.0% (hazard
ratio (HR) 0.68, 95% confidence interval (CI) 0.49 to 0.95, P value 0.027), and
three-year OS was 80% versus 69% (HR 0.68, 95% CI 0.49 to 0.95, P value 0.022).
However, as the CCRT chemotherapy differed between the two arms, we considered
the findings to be at high risk of bias.The second trial was a four-arm study
from which we extracted data on 463 women in two study arms receiving CCRT
(intravenous mitomycin C and oral 5-fluorouracil (5-FU)) or CCRT plus ACT (oral
5-FU for three cycles). The HR for OS in women who received ACT after CCRT
compared with the HR for OS in those who were given CCRT alone was 1.309 (95% CI
0.795 to 2.157), and the HR for disease-free survival (DFS) was 1.125 (95% CI
0.799 to 1.586).Haematological adverse events were more common in the ACT arms of
both trials. Quality of life (QoL) was not reported in either trial.
AUTHORS' CONCLUSIONS: With limited data from only two trials, we found
insufficient evidence to support the use of ACT after CCRT. Future large trials
are required to demonstrate efficacy, toxicities and QoL.
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