Short versus long duration infusions of paclitaxel for any advanced adenocarcinoma

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.

To assess the effectiveness and toxicity of short versus long infusions of paclitaxel for any advanced adenocarcinoma.

We searched the Cochrane Gynaecological Cancer Review Group Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2009, MEDLINE and EMBASE up to March 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included trials and contacted experts in the field, as well as drugs companies.

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

Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in meta-analyses.

We identified six trials that met our inclusion criteria. The trials compared 3, 24 and 96 hour infusions and one trial examined different schedules (1 versus 3 day). From the included RCTs we found no evidence of a difference between short and long infusions in terms of overall and progression-free survival and tumour non-response. In most cases a greater proportion of adverse events and severe toxicity occurred in the 24 hour infusion group compared to the 3 hour group with many of the analyses being highly statistically significant (RR = 0.32, 95% CI 0.22, 0.47, RR = 0.06, 95% CI 0.02, 0.17, RR = 0.59, 95% CI 0.40, 0.88, RR = 0.52, 95% CI 0.28, 0.97 for severe hypersensitivity, febrile neutropenia, sore mouth and diarrhoea outcomes respectively). Although a meta analysis of three trials found that 3 hour infusions were associated with a statistically significant increase in the risk of neurosensory changes compared with 24 hour infusions (RR = 1.26, 95% CI 1.09 to 1.46). Adverses events were not comprehensively reported for any of the other comparisons. Outcomes were incompletely documented and QoL outcomes were not reported in any of the trials. The strength of the evidence is weak in this review as it is based on meta analyses of very few trials or single trial analyses and all trials were at moderate risk of bias and two were published in abstract form only.

Ideally, large, multi-centre supporting trials are needed as outcomes were incompletely reported in included trials in this review. It may be beneficial to design a multi-arm trial comparing 3, 24 and 96 hour infusions or maybe looking at different schedules. In the absence of such trials, the decision to offer short or long infusions in advanced adenocarcinoma may need to be individualised, although it certainly appears that women have less toxicity, apart from sensory nerve damage, with a shorter infusion. Efficacy appearing similar regardless of infusion duration.