BackgroundThe National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials (RCTs).
ObjectivesTo review all known RCTs comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer.
Search strategyWe searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched.
Selection criteriaThis review includes RCTs in cervical cancer comparing concomitant chemoradiation with radiotherapy in the experimental arm. Trials allowing further adjuvant chemotherapy or hydroxyurea were incuded. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded.
Data collection and analysisTwo authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. Few trials reported acute toxicity adequately, but where possible ORs were calculated for the main types and severities of acute toxicity. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Late toxicity was rarely described in sifficient detail so could only be reviewed qualitatively.
More intense combination chemotherapy significantly improves the disease-free survival and the data indicate a modest improvement in OS. The addition of anthracyclines (e.g. doxorubicin) or the taxanes [e.g. paclitaxel (Taxol)] to cisplatin increases the response rate. More intensive regimens are associated with the gain in survival. However, grade 3 and 4 myelosuppression and gastrointestinal toxicity are also increased. Future developments are likely to exploit specific molecular characteristics of endometrial cancers, including their hormone dependence, growth factor target overexpression and PTEN loss. While no one drug or regimen offers a clear benefit for women with advanced endometrial cancer, platinum drugs, anthracyclines and paclitaxel seem the most promising agents. Future trials should address the impact of such agents on QoL and symptom control in addition to survival. Chemotherapy and endocrine therapy need to be compared directly in an RCT.
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