Gemcitabine — Drug Monograph

Brand names: Gemzar

Drug class: Antimetabolite

Mechanism of Action

Difluoronucleoside analog of deoxycytidine. Intracellular phosphorylation to gemcitabine triphosphate causes inhibition of ribonucleotide reductase (depletes dNTP pools) and incorporation into DNA causing chain termination — this "masked termination" avoids DNA repair. S-phase specific. Self-potentiating mechanism via RNR inhibition.

FDA Indications

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) — with cisplatin
• Locally advanced or metastatic pancreatic cancer
• Metastatic breast cancer — with paclitaxel (after anthracycline failure)
• Advanced ovarian cancer — with carboplatin (after platinum-based relapse)

Common Side Effects

• Myelosuppression (neutropenia, anemia, thrombocytopenia)
• Nausea and vomiting (low-moderate risk)
• Flu-like symptoms (fever, chills, myalgias) — characteristic
• Elevated liver enzymes (transient)
• Proteinuria, hematuria
• Rash
• Alopecia (mild)
• Peripheral edema

Clinical Pearl

Gemcitabine-associated pulmonary toxicity typically presents 2–4 weeks after initiation with acute dyspnea and fever. Chest CT shows bilateral infiltrates. Treatment is drug cessation and corticosteroids. The HUS/TTP syndrome associated with gemcitabine is rare but serious — look for new microangiopathic hemolytic anemia with thrombocytopenia after multiple cycles.

Related Therapies & Mechanisms

• Paclitaxel (Taxol) — Breast
• Carboplatin (Paraplatin) — Breast
• Doxorubicin (Adriamycin) — Breast
• Pembrolizumab (Keytruda) — NSCLC