Haematological Toxicity: Because Gemcitabine is a bone marrow suppressant, anaemia, leukopenia, and thrombocytopenia can occur as a result of administration of Gemcitabine. Myelosuppression is usually mild to moderate and is more pronounced for the granulocyte count. While two-thirds of patients experience some anaemia, only 7% have haemoglobin levels drop below 8 g/100 mL. While 19% of patients received transfusions, only 0.2% of patients discontinued because of anaemia. The white blood cell count is depressed in 61 % of patients, however only 9% of patients experience WBC's below 2000 cells/mm 3 and only 0.1% discontinued for leukopenia. Sixty-four percent of patients have reduced granulocyte counts and almost 25% drop below 1000 cells/mm 3 . Platelet counts are reduced in 21% of patients but only 5% of patients experience counts below 50,000 cells/mm 3 and only 0.4% of patients were discontinued due to thrombocytopenia. Previous therapy with cytotoxic agents appears to increase the frequency and severity of the leukopenia, granulocytopenia, and thrombocytopenia. There is no evidence of cumulative haematological toxicity. Anaemia is manageable with the use of conventional transfusions. Dose reduction or omission may be necessary for severe leukopenia or thrombocytopenia. Rare cases of haemorrhage occurring simultaneously with thrombocytopenia have been reported, but were usually thought to be disease-related. Thrombocythemia is also commonly reported (7.5% of patients), but no patients were discontinued for this event. Febrile neutropenia is also commonly reported.Hepatic Toxicity: Abnormalities of liver transaminase enzymes occur in about two-thirds of patients, but they are usually mild, non- progressive, and rarely necessitate stopping treatment. Less than 10% of patients experience elevations greater than 5 times normal and only 0.5% of patients were discontinued for abnormalities in liver function. One patient was discontinued for liver failure, but the assessment was complicated by a history of chronic alcoholism. Alanine transaminase (ALT) effects decline over time despite continued treatment. Elevations of alkaline phosphatase greater than 5 times normal occurred in 6.6% of patients but may have been due to bone disorders. Bilirubin values greater than 5 times normal were observed in 1.5% of patients, but ninety percent of patients had normal bilirubin levels.Gastrointestinal: Nausea, and nausea accompanied by vomiting are each reported in about one-third of patients, respectively. This adverse event requires therapy in about 20% of patients, is rarely dose-limiting, and is easily manageable with standard antiemetics. Only 0.9% of patients report intractable vomiting and only 0.9% of patients discontinued due to nausea and vomiting. Diarrhoea and stomatitis are commonly reported. Diarrhoea (transient to tolerable) was reported by 7% of patients. Intolerable diarrhoea requiring therapy was reported in 0.5% of patients. No patients discontinued treatment because of diarrhoea.Genito-Urinary Toxicity: Mild proteinuria and haematuria are reported in approximately half the patients, but are rarely clinically significant, and are not usually associated with any change in serum creatinine or blood urea nitrogen. However, a few cases (0.6% of patients) of renal failure of uncertain aetiology have been reported hence Gemcitabine should be used with caution in patients with impaired renal function. Rare cases (0.4%) of possible haemolytic uraemic syndrome have been reported. Cumulative renal toxicity has not been observed.Pulmonary Toxicity: Dyspnoea occurring within hours following Gemcitabine injection is reported by approximately 10% of patients. This dyspnoea is usually mild and short-lived, rarely dose-limiting, and usually abates spontaneously without any specific therapy. The mechanism of this toxicity is unknown and the relationship to Gemcitabine is not clear. Only 0.6% of patients discontinued due to dyspnoea and only 0.1 % of these were believed to be medicine-related. Interstitial pneumonitis has been reported infrequently.Allergic Toxicity: A rash is seen in approximately 25% of patients and is associated with pruritus in about 10% of patients. The rash is usually mild, not dose-limiting, and responds to local therapy. Desquamation, vesiculation, and ulceration have been reported rarely. Discontinuations for cutaneous toxicity were reported for only 0.3% of patients. Gemcitabine is well tolerated during the infusion with only a few cases of injection site reaction reported. Gemcitabine does not appear to be a vesicant. There have been no reports of injection site necrosis. Bronchospasm is usually mild and transient, but parenteral therapy may be required. Gemcitabine should not be administered to patients with a known hypersensitivity to the medicine.Neurotoxicity: Mild to moderate somnolence occurs in approximately 10% of patients. Only 0.1 % of patients discontinued for somnolence. Asthenia is frequently reported with other flu symptoms but is also reported as an isolated symptom. Asthenia was cause for discontinuation by 1.4% of patients. Paresthesias are reported in 3.4% of patients, but only 0.2% report these as severe. Oedema/Peripheral Oedema : Oedema/peripheral oedema is reported by approximately 30% of patients. Some cases of facial oedema have also been reported. Pulmonary oedema was reported infrequently (1%). Oedema/peripheral oedema is usually mild to moderate, rarely dose-limiting, is sometimes reported as painful and is usually reversible after stopping Gemcitabine treatment. The mechanism of this toxicity is unknown. However, it was not associated with any evidence of cardiac, renal or hepatic failure. Oedema resulted in the discontinuation of 0.7% of patients.Alopecia: Overall, 86.7% of patients had no hair loss at all. Minimal to moderate hair loss was reported by 13% of patients. Only 0.5% of patients reported complete but reversible alopecia.
