Adjuvant platinum-based chemotherapy for early stage cervical cancer. 2012

Daniela D Rosa, and Lídia R F Medeiros, and Maria I Edelweiss, and Paula R Pohlmann, and Airton T Stein
OncologyUnit,HospitalMoinhos deVento, PortoAlegre,Brazil. dornellesrosa@hotmail.com

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.

UI MeSH Term Description Entries
D007044 Hysterectomy Excision of the uterus. Hysterectomies
D009367 Neoplasm Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D002583 Uterine Cervical Neoplasms Tumors or cancer of the UTERINE CERVIX. Cancer of Cervix,Cancer of the Cervix,Cancer of the Uterine Cervix,Cervical Cancer,Cervical Neoplasms,Cervix Cancer,Cervix Neoplasms,Neoplasms, Cervical,Neoplasms, Cervix,Uterine Cervical Cancer,Cancer, Cervical,Cancer, Cervix,Cancer, Uterine Cervical,Cervical Cancer, Uterine,Cervical Cancers,Cervical Neoplasm,Cervical Neoplasm, Uterine,Cervix Neoplasm,Neoplasm, Cervix,Neoplasm, Uterine Cervical,Uterine Cervical Cancers,Uterine Cervical Neoplasm
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D005260 Female Females
D005472 Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid. 5-FU,5-FU Lederle,5-FU Medac,5-Fluorouracil,5-Fluorouracil-Biosyn,5-HU Hexal,5FU,Adrucil,Carac,Efudex,Efudix,Fluoro-Uracile ICN,Fluoroplex,Fluorouracil Mononitrate,Fluorouracil Monopotassium Salt,Fluorouracil Monosodium Salt,Fluorouracil Potassium Salt,Fluorouracil-GRY,Fluorouracile Dakota,Fluorouracilo Ferrer Far,Fluoruracil,Fluracedyl,Flurodex,Haemato-FU,Neofluor,Onkofluor,Ribofluor,5 FU Lederle,5 FU Medac,5 Fluorouracil,5 Fluorouracil Biosyn,5 HU Hexal,Dakota, Fluorouracile,Fluoro Uracile ICN,Fluorouracil GRY,Haemato FU
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000971 Antineoplastic Combined Chemotherapy Protocols The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form. Anticancer Drug Combinations,Antineoplastic Agents, Combined,Antineoplastic Chemotherapy Protocols,Antineoplastic Drug Combinations,Cancer Chemotherapy Protocols,Chemotherapy Protocols, Antineoplastic,Drug Combinations, Antineoplastic,Antineoplastic Combined Chemotherapy Regimens,Combined Antineoplastic Agents,Agent, Combined Antineoplastic,Agents, Combined Antineoplastic,Anticancer Drug Combination,Antineoplastic Agent, Combined,Antineoplastic Chemotherapy Protocol,Antineoplastic Drug Combination,Cancer Chemotherapy Protocol,Chemotherapy Protocol, Antineoplastic,Chemotherapy Protocol, Cancer,Chemotherapy Protocols, Cancer,Combinations, Antineoplastic Drug,Combined Antineoplastic Agent,Drug Combination, Anticancer,Drug Combination, Antineoplastic,Drug Combinations, Anticancer,Protocol, Antineoplastic Chemotherapy,Protocol, Cancer Chemotherapy,Protocols, Antineoplastic Chemotherapy,Protocols, Cancer Chemotherapy
D016032 Randomized Controlled Trials as Topic Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical
D017024 Chemotherapy, Adjuvant Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment. Adjuvant Chemotherapy,Drug Therapy, Adjuvant,Adjuvant Drug Therapy

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