Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of the uterine cervix.

BACKGROUND

A number of randomised studies suggest hydroxyurea given alongside radiotherapy improves survival in patients with locally advanced cervix cancer. Following publication of five large randomised trials in 1999 and 2000 concomitant chemoradiotherapy has become standard treatment for these patients. In two of the studies hydroxyurea was given to patients in both control and experimental arms. The precise role of this orally administered cytotoxic drug is not known.

OBJECTIVES

To assess the effectiveness (survival and toxicity) of concomitant radiation and hydroxyurea compared with radiotherapy alone in treating locally advanced cervix cancer.

SEARCH STRATEGY

We searched the following:Cochrane Gynaecological Cancer Group's Specialised RegisterCENTRAL (Cochrane Library on CD ROM, issue 4, 2002) MEDLINE (Silver Platter, from 1970 to 2001) EMBASE (from 1980 to 2001) CANCERLIT (from 1970 to 2001) PDQ (search for open and closed trials) LILACSMeta-register (ongoing trials)Searches were not language or publication restricted. Investigators of relevant trials were contacted for further information.

SELECTION CRITERIA

Randomized controlled trials comparing concomitant radiotherapy (+/- surgery) with hydroxyurea versus radiotherapy (+/- surgery) for locally advanced cervix cancer.

DATA COLLECTION AND ANALYSIS

Two authors independently reviewed trials for inclusion and extracted data. Discussions on all aspects of data collection and analysis took place among all the authors at regular intervals.

MAIN RESULTS

Seven studies were found to be suitable for inclusion from 33 identified as relevant. None of the trials provided adequate evidence to support the use of hydroxyurea owing to small sample size, large numbers of post-randomisation exclusions and questionable rules for censoring, particularly a failure to include treatment-related deaths in the survival analysis. Details of statistical analysis were limited and often confusing, and we felt meta-analysis would lead to unreliable and invalid conclusions. Most studies appeared to be double blind placebo-controlled studies but none give details of power calculations or reasons for stopping recruitment. Only two studies had more than 50 patients. Patients were excluded from analysis in most trials for treatment-related reasons; in one, less than half those recruited were used in the analysis, the remainder having been excluded because of tumour progression or treatment-related conditions e.g. septicaemia, worsening renal/hepatic function. In another trial five out of 20 in the hydroxyurea group died of treatment-related complications but the five-year survival group was presented as 94%.

REVIEWER'S CONCLUSIONS: We found no evidence to support the use of hydroxyurea in addition to radiotherapy in the routine treatment of cervix cancer.