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Int J Clin Pharmacol Res. 1996;16(1):9-18.

Gemcitabine: safety profile unaffected by starting dose.

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Lilly Research Centre, Windlesham, Surrey, UK.


Gemcitabine, a novel anticancer agent, has been shown to be active in several human solid tumours, including non-small cell lung cancer and pancreatic cancer. In addition, gemcitabine has been noted to have a particularly mild safety profile for such an active agent and is lacking some of the classical toxicities of oncolytics, i.e. alopecia, severe nausea and vomiting, and mucositis. Therefore, the safety data from 790 patients in 18 completed clinical studies were integrated to study its toxicity profile in more detail. In all of these studies gemcitabine was administered as a 30-minute intravenous infusion every week for three weeks followed by a week of rest (one cycle). This integrated database confirmed that gemcitabine is well tolerated. Its haematological toxicity was mild and short lasting. The low incidence of infection was correspondingly low. Transaminase elevations occurred frequently, but they were usually mild and rarely dose-limiting. Mild proteinuria and haematuria were seen but were rarely clinically significant. There was no evidence of cumulative hepatic or renal toxicity. Nausea and vomiting were mild, rarely dose-limiting and generally well controlled with standard antiemetics. Flu-like symptoms were experienced in a proportion of patients but were short-lasting. Where oedema or peripheral oedema were experienced, there was no evidence of any association with cardiac, hepatic or renal failure. Hair loss was rare. The integrated database was also analysed according to starting dose (800, 1000 or 1250 mg/m2) in a subset of 665 chemonaive patients to see whether an increased dose resulted in increased toxicity. In general, only small, clinically insignificant differences in toxicity were seen between the three dose groups. Although segmented neutrophil count appeared to increase as starting dose increased (grade 3 or 4, 19.4%, 23.2%, 28.3% respectively), this was not associated with an increased incidence of infection. In some cases, toxicity decreased with increasing dose but this may have been because of imbalances between the patient groups. These findings indicate that not only is gemcitabine well tolerated, but it also has a broad therapeutic index and the use of higher doses may be possible.

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