What are the side effects of Gemzar (gemcitabine)?

Gemzar (Gemcitabine) Side Effects

Gemcitabine has a notably mild toxicity profile compared to other cytotoxic agents, with myelosuppression being the primary concern, while severe non-hematologic toxicities are uncommon. 1

Hematologic Toxicities (Most Common)

Myelosuppression is the dose-limiting toxicity but is typically short-lived and rarely clinically significant. 1, 2

• Neutropenia: Grade 3-4 occurs in 19-25% of patients as monotherapy 1, 2
• Anemia: Grade 3-4 in 7-8% of patients; red blood cell transfusions required in 19% 1
• Thrombocytopenia: Grade 3-4 in 4-5% of patients 1, 2
• Febrile neutropenia: Uncommon at 5% when used in combination regimens 3

The myelosuppression is schedule-dependent, with more severe toxicity when gemcitabine is administered more frequently than weekly. 1

Hepatic Toxicities

Transaminase elevations occur frequently but are usually mild and rarely dose-limiting. 1, 2

• Elevated ALT: Occurs in 68% of patients (Grade 3-4 in 10%) 1
• Elevated AST: Occurs in 67% of patients (Grade 3-4 in 8%) 1
• Elevated alkaline phosphatase: Occurs in 55% of patients (Grade 3-4 in 9%) 1
• No cumulative hepatic toxicity has been demonstrated with continued treatment 2

Renal Toxicities

Mild proteinuria and hematuria are common but rarely clinically significant. 1, 2

• Proteinuria: Occurs in 45% of patients (Grade 3-4 in <1%) 1
• Hematuria: Occurs in 35% of patients (Grade 3-4 in <1%) 1
• Renal failure: Rare but reported; hemolytic uremic syndrome is a serious but uncommon complication requiring permanent discontinuation 1
• No cumulative renal toxicity with continued treatment 2

Gastrointestinal Toxicities

Nausea and vomiting are mild and generally well controlled with standard antiemetics. 1, 2

• Nausea/vomiting: Occurs in 69% of patients (Grade 3-4 in 14%) 1
• Diarrhea: Occurs in 19-25% of patients (Grade 3 in 1-3%) 1
• Constipation: Occurs in 42% when combined with carboplatin 1
• Stomatitis: Occurs in 11% of patients (Grade 3-4 in <1%) 1

Dermatologic and Constitutional Symptoms

Alopecia is rare with gemcitabine, distinguishing it from most cytotoxic agents. 2, 4

• Alopecia: Grade 3 in only 0.5% of patients; no Grade 4 alopecia reported 2
• Rash: Occurs in 30% of patients (Grade 3 in <1%) 1
• Flu-like symptoms: Occur in 19% of patients, including fever (41%), asthenia, headache, myalgia 1, 2

Pulmonary Toxicities

Dyspnea is common, but severe pulmonary toxicity and respiratory failure are rare but serious complications requiring permanent discontinuation. 1

• Dyspnea: Occurs in 23% of patients (Grade 3 in 3%) 1
• Pulmonary toxicity: Grade 3-4 in 1.4% of patients 4
• Respiratory failure: Can occur and requires immediate discontinuation 1

Edema

Peripheral edema occurs in 20% of patients and is typically mild, but severe cases may require corticosteroids and drug discontinuation. 1, 5

• Peripheral edema: Occurs in 20% of patients without cardiac, hepatic, or renal failure 1, 4
• Severe edema (Grade ≥2): Occurs in <1% of patients 5
• Risk factors: Pre-existing edema increases risk of severe gemcitabine-induced edema 5
• Management: Severe cases require gemcitabine suspension and corticosteroid treatment; permanent discontinuation may be necessary 5

Rare but Serious Toxicities

Several rare but life-threatening toxicities require immediate recognition and permanent discontinuation of gemcitabine. 1

• Capillary leak syndrome: Severe consequences reported; permanently discontinue if develops 1
• Posterior reversible encephalopathy syndrome (PRES): Presents with headache, seizure, confusion, visual disturbances; confirm with MRI and permanently discontinue 1
• Hemolytic uremic syndrome: Requires permanent discontinuation 1
• Radiation recall: Reported in patients receiving gemcitabine after prior radiation 1
• Cardiac effects: Slow intra-atrial conduction and atrial fibrillation reported 3

Combination Therapy Considerations

When gemcitabine is combined with other agents, toxicity profiles overlap and intensify. 3

• Gemcitabine plus ramucirumab: Grade 3-4 adverse events in 44% (neutropenia, hypertension, fatigue most common); thromboembolism in 4% 3
• Gemcitabine plus carboplatin: Higher rates of nausea (69%), alopecia (49%), and fatigue (40%) compared to carboplatin alone 1
• High-dose gemcitabine (1,250 mg/m²): Grade ≥3 adverse events in 57%, including fatal infection 3

Common Pitfalls to Avoid

• Do not attribute new symptoms solely to chemotherapy without excluding disease progression, particularly gastric outlet obstruction presenting as nausea/vomiting or peritoneal carcinomatosis presenting as bloating 3
• Do not overlook schedule-dependent toxicity; more frequent dosing than weekly significantly increases myelosuppression 1
• Do not ignore sudden clinical deterioration in patients on gemcitabine, as bleeding, thromboembolism, or infection may develop abruptly 3
• Do not use gemcitabine concurrently with radiation (within 7 days) due to excessive toxicity; radiation recall can occur even when given sequentially 1