Short versus long duration infusions of paclitaxel for any advanced adenocarcinoma

 

Abstract

Background

Paclitaxel has become a standard drug used in a number of common cancers. At first long infusions were used to reduce the rate of inflow of the drug and as a result reduce the occurrence of hypersensitivity types of allergic reactions. Trials with shorter durations of infusion, and using a cocktail of anti-allergic drugs to prevent hypersensitivity reactions, some randomised, were begun. These were interpreted as showing that effectiveness of treatment was not lessened by a short infusion time. These studies also appeared to show that some important toxicities were less common with short infusions and that they were more convenient for the patient and the hospital.

Objectives

To assess the effect of varying the duration of infusion of paclitaxel on its anti-cancer effectiveness and side-effects.

Search strategy

Electronic searches of the Cochrane Gynaecological Cancer CRG, the Cochrane Register of Controlled Trials, MEDLINE, EmBase, CANCERLIT, PDQ, Meta-register (mRCT) and the
M.D.Anderson Cancer Centre, GOG were carried out.
Information from the manufacturer and authors of reports of studies was also acquired.

Selection criteria

The review was restricted to randomised controlled trials of single agent paclitaxel or paclitaxel with other drugs, where the only variable was the duration of paclitaxel infusion. The review only included patients with advanced adenocarcinoma.

Data collection and analysis

Data was extracted by two independent reviewers and where there was disagreement this was resolved by discussion. Where possible the data was synthesised in a meta-analysis.

Main results

Three hour paclitaxel infusions appear to result in a smaller fall in white blood cell count, less fever, infection and sore mouth than 24 hour infusions. In contrast, 24 hour infusions cause less nerve toxicity. Other side-effects are not dependent on the duration of infusion. Evidence from individual trials suggesting efficacy may be slightly greater with 24 hour infusions is inconclusive. Combination of data from trials of different cancer sites in a meta-analysis must be considered speculative, but the combined data also suggest that 24 hour infusions of paclitaxel may be slightly more effective.

Authors' conclusions

This review confirms that, apart from neurological effects, three hour infusion of paclitaxel causes significantly less side effects than 24 hour infusion. Insufficient data exists to state whether varying the duration of infusion has a significant effect on its anti-cancer effectiveness. Further study would be required to establish whether there genuinely is a significant difference in efficacy according to the duration of infusion of paclitaxel.

 

Plain language summary

Short-infusion paclitaxel (anticancer drug) causes fewer adverse effects than 24-hour infusion, is more convenient, with no obvious loss of effectiveness

Paclitaxel is derived from Yews, and used for several cancers. It was initially given by a long infusion (24 hours), with premedication to avoid allergic reactions. It was also thought this method would be more active against tumours. However, this review found that short (three hour) infusions are more convenient and cause significantly less adverse effects (decreased white blood cell counts, fever, infection, sore mouths). There is no obvious loss of effectiveness, although further trials are needed to be sure.