Gemcitabine (Gemzar)

Indications


Contraindications

  • Concurrent Radiotherapy (Due to Radiosensitization) (see Radiation Therapy, [[Radiation Therapy]]): due to risk of mucositis/esophagitis/pneumonitis

Pharmacology

  • Pyrimidine Analog Which Impairs DNA Synthesis: cell cycle-specific for the S-phase (but also blocks progression at the G1/S-phase)
    • Gemcitabine is Phosphorylated Intracellularly by Deoxycytidine Kinase to Form Gemcitabine Monophosphate: gemcitabine monophosphate is subsequently phosphorylated to form gemcitabine diphosphate and gemcitabine triphosphate
    • Gemcitabine Triphosphate Incorporates into DNA and Inhibits DNA Polymerase
    • Gemcitabine Diphosphate Inhibits Ribonucleotide Reductase

Administration

  • IV

Dose Adjustment

  • Hepatic: no dosage adjustments provided in manufacturer labeling
    • Transaminitis: no dosage adjustment
    • Serum Bilirubin >1.6 g/dL: use initial dose of 800 mg/m2
  • Renal: no dosage adjustments provided in manufacturer labeling
    • In Patient on Hemodialysis: hemodialysis should begin 6-12 hrs after gemcitabine infusion

Adverse Effects

Allergic/Immunologic Adverse Effects

  • Anaphylaxis/Laryngeal Edema (see Anaphylaxis, [[Anaphylaxis]])

Cardiovascular Adverse Effects

  • Peripheral Edema (see Peripheral Edema, [[Peripheral Edema]])
    • Epidemiology: occurs in 20% of cases

Dermatologic Adverse Effects

  • Alopecia
    • Epidemiology: occurs in 15% of cases
  • Rash
    • Epidemiology: occurs in 30% of cases

Gastrointestinal Adverse Effects

  • Diarrhea (see Diarrhea, [[Diarrhea]])
    • Epidemiology: occurs in 19% of cases
  • Elevated Liver Function Tests (LFT’s) (see Drug-Induced Hepatotoxicity, [[Drug-Induced Hepatotoxicity]])
    • Elevated Alkaline Phosphatase: occurs in 55% of cases
    • Hyperbilirubinemia: occurs in 13% of cases
    • Transaminitis: occurs in 67-68% of cases
  • Hepatic Failure (see xxxx, [[xxxx]])
  • Nausea (see Nausea and Vomiting, [[Nausea and Vomiting]])
    • Epidemiology: occurs in 69% of cases
  • Stomatitis
    • Epidemiology: occurs in 11% of cases

Hematologic Adverse Effects

  • Hemolytic-Uremic Syndrome (HUS)/Thrombotic Thrombocytopenic Purpura (TTP) (see Hemolytic-Uremic Syndrome, [[Hemolytic-Uremic Syndrome]] and Thrombotic Thrombocytopenic Purpura, [[Thrombotic Thrombocytopenic Purpura]])
    • Epidemiology: case reports
  • Myelosuppression/Pancytopenia (see Pancytopenia, [[Pancytopenia]])
    • General Comments: myelosuppression is usually the dose-limiting toxicity and is increased by concomitant use of other myelosuppressive agents
    • Anemia (see Anemia, [[Anemia]])
    • Leukopenia/Neutropenia(see Leukopenia, [[Leukopenia]] and Neutropenia, [[Neutropenia]])
    • Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])

Neurologic Adverse Effects

Pulmonary Adverse Effects

General Comments

  • Onset of Pulmonary Toxicity: may be delayed up to 2 wks after the last dose

Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])

  • Epidemiology
    • Occurs in 0.1-7% of cases
    • Increased risk of lung toxicity when used in combination with Docetaxel (see Docetaxel, [[Docetaxel]]) [MEDLINE]
  • Physiology: capillary leak
  • Diagnosis: CXR/CT with mixed alveolar and interstitial infiltrates
  • Clinical: may progress to severe infiltrates within hours of infusion
  • Treatment/Prognosis: withdrawal of drug -> usually resolves, although corticosteroids may be required

Bronchospasm (see Obstructive Lung Disease, [[Obstructive Lung Disease]])

  • Epidemiology: occurs in <2% of cases

Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])

  • Epidemiology: case reports

Dyspnea (see Dyspnea, [[Dyspnea]])

  • Epidemiology: occurs in 10% of patients (severe dyspnea occurs in 5% of patients)
  • Clinical: usually non-specific dyspnea occurring within hours-days of treatment
  • Prognosis: usually self-limited

Interstitial Pulmonary Fibrosis (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]])

  • Epidemiology: xxx

Pulmonary Veno-Occlusive Disease (see Pulmonary Veno-Occlusive Disease, [[Pulmonary Veno-Occlusive Disease]])

  • Epidemiology: case reports

Renal Adverse Effects

  • Increased Blood Urea Nitrogen (see Increased Blood Urea Nitrogen, [[Increased Blood Urea Nitrogen]]): 16% of cases
  • Hematuria (see Hematuria, [[Hematuria]])
    • Epidemiology: occurs in 35% of cases

Other Adverse Effects

  • Flu-Like Symptoms: occurs in 19% of cases
  • Infection: occurs in 16% of cases
  • Radiation Recall (see Radiation Therapy, [[Radiation Therapy]]): when radiation and gemcitabine are administered >7 days apart
  • Radiosensitization (see Radiation Therapy, [[Radiation Therapy]]): when radiation and gemcitabine are administered < or equal to 7 days apart

References

  • Fatal pulmonary toxicity resulting from treatment with gemcitabine. Cancer 1997; 80: 286-291
  • Pulmonary toxicity from treatment with gemcitabine. J Cancer Res Clin Oncol 1998; 124: R163
  • Diffuse alveolar damage in a patient treated with gemcitabine. Eur Respir J 1998; 11: 504-506
  • Activity of gemcitabine in non-small-cell lung cancer: results of the Japan gemcitabine group (A) phase II study. Cancer Chemother Pharmacol 1998; 41: 217-222
  • Fatal pulmonary toxicity resulting from treatment with gemcitabine. Cancer 1998; 82: 1800-1801
  • Successful treatment of gemcitabine toxicity with a brief course of oral corticosteroid therapy. Chest 1998; 114: 1779-1781
  • Fatal pulmonary toxicity resulting from treatment with gemcitabine and vinorelbine association. Chest 1999; 116: 316
  • Sudden cardiopulmonary toxicity following a single infusion of gemcitabine. Annals of Oncology 1999; 10: 997
  • Severe pulmonary toxicity in patients treated with a combination of docetaxel and gemcitabine for metastatic transitional cell carcinoma. Annals of Oncology 1999; 10: 943-947 [MEDLINE]
  • Pulmonary toxicity resulting from treatment with gemcitabine. Onkologie 1999; 22: 146-149
  • Severe nonhematologic toxicity after treatment with gemcitabine. Proceedings of the American Society of Clinical Oncology 1999; 18: 598a
  • Non-cardiogenic pulmonary edema during gemcitabine-therapy in 5 patients with bronchial carcinoma. Atemwegs and Lungenkrankheiten 1999; 25: 187
  • Acute interstitial pneumonitis related to gemcitabine. J Clin Oncol 2000; 18: 697-698
  • Gemcitabine pulmonary toxicity: CT features. Journal of Computer Assisted Tomography 2000; 24: 977-980
  • Chemotherapy-induced noncardiogenic pulmonary edema related to gemcitabine plus docetaxel combination with granulocyte colony-stimulating factor support. Respiration 2000; 67: 680-3
  • Severe acute lung injury induced by gemcitabine. Neth J Med 2000; 56: 232-235
  • Infrequency of serious pumonary toxicity (SPT) with gemzar (G): analysis of a large database. Proc Am Soc Clin Oncol 2000; 19: 196a
  • Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study. European Journal of Cancer 2000; 36: 2329-2334
  • Gemcitabine-associated diffuse alveolar hemorrhage. Intensive Care Medicine 2001; 27: 1554
  • Adult respiratory distress syndrome after antineoplastic chemotherapy: probable effect of gemcitabine. Presse Medicale 2001; 30: 851-854
  • Gemcitabine-induced systemic capillary leak syndrome. Annals of Oncology 2001; 12: 1651-1652
  • Radiation recall reaction following gemcitabine. Lung Cancer 2001; 33: 299-302
  • Fatal pulmonary veno-occlusive disease possibly related to gemcitabine. Lung Cancer 2001; 31: 83-85
  • Gemcitabine added to doxorubicin, bleomycin, and vinblastine for the treatment of de novo Hodgkin disease: unacceptable acute pulmonary toxicity. Cancer 2003; 98: 978-82
    High incidence of pulmonary toxicity of weekly docetaxel and gemcitabine in patients with non-small cell lung cancer: results of a dose-finding study. Lung Cancer; Volume 44, Issue 3, June 2004, Pages 363-368
  • A prospective study on lung toxicity in patients treated with gemcitabine and carboplatin: clinical, radiological and functional assessment. Annals of Oncology 2004; 15: 1250-1255
  • High incidence of pulmonary toxicity of weekly docetaxel and gemcitabine in patients with non-small cell lung cancer: results of a dose-finding study. Lung Cancer; Volume 44, Issue 3, June 2004, Pages 363-368
  • Severe gemcitabine-induced capillary-leak syndrome mimicking cardiac failure in a patient with advanced pancreatic cancer and high-risk cardiovascular disease. Clinical Oncology 2004; 16: 577-579
  • Hemolytic uremic syndrome as a complication of gemcitabine treatment: report of six cases and review of the literature. Revue de Medecine Interne 2005; 26: 179-188
  • Gemcitabine Pulmonary Toxicity in Ovarian Cancer. The Oncologist July 2008 vol. 13 no. 7 807-811
  • Thrombotic thrombocytopenic purpura and gemcitabine. Case Rep Oncol. 2011 Jan;4(1):143-8. doi: 10.1159/000326801 [MEDLINE]