SAFETY PROFILE OF GEMCITABINE

This paper reviews the toxicity profile of gemcitabine in a large grou p of patients (up to 790) from pivotal phase II studies, in which the drug was given intravenously as a 30 min infusion, in a schedule once a week for 3 weeks followed by a week of rest. The safety profile of g emcitabine is unusually mild for such an active agent in solid tumours . Haematological toxicity is mild and short-lived with modest WHO grad es 3 and 4 for haemoglobin (6.4% and 0.9% of patients), leukocytes (8. 1% and 0.5%), neutrophils (18.7% and 5.7%) and platelets (6.4% and 0.9 %). The incidence of grade 3 and 4 infection associated with this leve l of myelosuppression was low (0.9% and 0.2%). Transaminase elevations occurred frequently, but they were usually mild, and rarely dose limi ting. Mild proteinuria and haematuria were seen but were rarely clinic ally significant. There was no evidence of cumulative hepatic or renal toxicity. Nausea and vomiting was mild, rarely dose limiting, and gen erally well controlled with standard antiemetics. Flu-like symptoms we re experienced in a small proportion of patients but were of short dur ation. Where oedema/peripheral oedema was experienced there was no evi dence of any association with cardiac, hepatic or renal failure. Hair loss was rare, with WHO grade 3 alopecia reported in 0.5% of patients. There was no grade 4 alopecia. Furthermore, gemcitabine displayed min imal toxicity in elderly patients, and the side-effect profile does no t seem to be affected by patient age. The adverse events typically exp erienced with cytotoxic agents, namely myelosuppression, nausea and vo miting and alopecia, are not seen to such a degree with gemcitabine, a nd this nonoverlapping toxicity profile suggests that gemcitabine is a promising agent for incorporation into combination chemotherapy regim ens.