erlotinib


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erlotinib

Tarceva

Pharmacologic class: Epidermal growth factor receptor (EGFR) inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Unclear. Drug inhibits intracellular phosphorylation of tyrosine kinase associated with EGFR, which is expressed on cell surface of both normal cells and cancer cells.

Availability

Tablets: 25 mg, 100 mg, 150 mg

Indications and dosages

Locally advanced or metastatic non-small-cell lung cancer after failure of at least one chemotherapy regimen; maintenance treatment in patients whose disease hasn't progressed after four cycles of platinumbased first-line chemotherapy

Adults: 150 mg P.O. at least 1 hour before or 2 hours after food ingestion, continued until disease progresses or unacceptable toxicity occurs

First-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer (given with gemcitabine)

Adults: 100 mg P.O. daily at least 1 hour before or 2 hours after food ingestion, continued until disease progresses or unacceptable toxicity occurs

Dosage adjustment

• Severe diarrhea
• Pretreatment with CYP3A4 inducers
• Concurrent use of potent CYP3A4 inhibitors (such as ketoconazole)
• Acute onset of new or progressing pulmonary symptoms

Off-label uses

• Colorectal and renal cell cancer
• Malignant glioma

Contraindications

None

Precautions

Use cautiously in:
• hepatic impairment, diarrhea
• pulmonary symptoms, suspected interstitial lung disease (such as pneumonitis, interstitial pneumonia, obliterative bronchiolitis, pulmonary fibrosis, adult respiratory distress syndrome, or lung filtration)
• concomitant use of anti-angiogenic agents, corticosteroids, nonsteroidal anti-inflammatory drugs, or taxane-based chemotherapy; prior history of peptic ulceration or diverticular disease
• concurrent warfarin therapy
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Give at least 1 hour before or 2 hours after food ingestion.

Interrupt therapy if patient develops acute onset of new or progressing pulmonary symptoms pending diagnostic evaluation. If interstitial lung disease develops, discontinue drug and administer appropriate interventions.

Be aware that some cases of hepatorenal syndrome, acute renal failure, and renal insufficiency may be secondary to baseline hepatic impairment while others may be associated with severe dehydration. Interrupt therapy and take appropriate measures to intensively rehydrate patient, as needed.

Discontinue drug if total bilirubin level is above three times upper limit of normal (ULN) or transaminase levels are above five times ULN versus pretreatment values; signs and symptoms of GI perforation occur; severe bullous, blistering, or exfoliating conditions develop; or acute or worsening ocular disorders such as eye pain occur.

Adverse reactions

CNS: fatigue

EENT: conjunctivitis, keratoconjunctivitis sicca corneal perforation and ulceration

GI: nausea, vomiting, diarrhea, abdominal pain, anorexia, stomatitis GI perforation

GU: renal insufficiency, acute renal failure

Hepatic: hepatorenal syndrome, hepatic failure

Respiratory: dyspnea, cough, interstitial lung disease

Skin: rash, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis-like reactions

Other: infection

Interactions

Drug-drug.CYP3A4 inhibitors (such as clarithromycin, indinavir, itraconazole, ketoconazole, ritonavir, saquinavir, telithromycin): increased erlotinib blood level

CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampin): decreased erlotinib blood level

Warfarin, other coumarin anticoagulants: elevated INR, increased bleeding risk

Drug-diagnostic tests.Alanine aminotransferase, aspartate aminotransferase, bilirubin: increased

International Normalized Ratio: increased

Liver function tests: abnormal

Drug-food.Any food: increased erlotinib bioavailability

Drug-herb.Coenzyme Q10: decreased chemotherapy efficacy

St. John's wort: decreased erlotinib blood level

Drug-behaviors.Smoking: decreased erlotinib plasma concentration

Patient monitoring

Perform periodic serum electrolyte measurements and renal and liver function testing.
• Advise patient not to smoke while taking drug.
• Monitor INR and prothrombin time regularly in patients receiving warfarin, other coumarin anticoagulants, or nonsteroidal anti-inflammatory drugs.

Monitor for signs and symptoms of respiratory disorders and GI perforation.

Patient teaching

Advise patient to seek immediate medical attention for severe or persistent diarrhea, nausea, vomiting, anorexia, severe rash, eye pain, eye irritation, or onset or worsening of unexplained shortness of breath or cough.
• Advise patient not to smoke while taking drug.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

erlotinib

(er-lo-ti-nib) ,

Tarceva

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: enzyme inhibitors
Pregnancy Category: D

Indications

genetic implication First-line therapy of metastatic non–small-cell lung cancer that has epidermal growth factor exon 19 deletions or exon 21 substitution mutations.Maintenance treatment of locally advanced/metastatic non–small-cell lung cancer when disease has not progressed after four cycles of platinum-based first-line chemotherapy.Locally advanced/metastatic non–small-cell lung cancer that has not responded to ≥1 previous chemotherapy regimenFirst-line therapy for locally advanced, surgically unresectable, or metastatic pancreatic cancer (with gemcitabine).

Action

genetic implication Inhibits the enzyme tyrosine kinase, which is associated with human epidermal growth factor receptor (EGFR); blocks growth stimulation signals in cancer cells.

Therapeutic effects

Decreased spread of lung or pancreatic cancer with increased survival.

Pharmacokinetics

Absorption: 60% absorbed; bioavailability ↑ to 100% with food.
Distribution: Unknown.
Protein Binding: 93% protein bound.
Metabolism and Excretion: Mostly metabolized by the liver (CYP3A4 enzyme system).
Half-life: 36 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
Oralunknown4 hr24 hr

Contraindications/Precautions

Contraindicated in: Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Hepatic impairment;Previous chemotherapy/radiation, pre-existing lung disease, metastatic lung disease (may ↑ risk of interstitial lung disease);Patients with child-bearing potential; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • cerebrovascular accident (pancreatic cancer patients) (life-threatening)
  • fatigue

Cardiovascular

  • myocardial infarction/ischemia (pancreatic cancer patients) (life-threatening)

Ear, Eye, Nose, Throat

  • conjunctivitis
  • corneal perforation
  • corneal ulceration

Respiratory

  • interstitial lung disease (life-threatening)
  • dyspnea (most frequent)
  • cough

Gastrointestinal

  • hepatotoxicity
  • gi perforation (life-threatening)
  • diarrhea (most frequent)
  • abdominal pain
  • anorexia
  • nausea
  • stomatitis
  • vomiting
  • ↑ liver enzymes

Dermatologic

  • bullous and exfoliative skin disorders (life-threatening)
  • rash (most frequent)
  • dry skin
  • pruritus

Genitourinary

  • renal failure (life-threatening)

Hematologic

  • microangiopathic hemolytic anemia with thrombocytopenia (pancreatic cancer patients)

Interactions

Drug-Drug interaction

Strong inhibitors of CYP3A4, including atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole ↑ levels and the risk of toxicity; consider dose reduction.Strong inducers of CYP3A4, including rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, or phenobarbital ↓ levels and may ↓ response; alternative therapy or ↑ dose should be considered.Ciprofloxacin may ↑ levels and the risk of toxicity.Smoking may ↓ levels and may ↓ response; may consider ↑ dose if smoking continues.May ↓ midazolam levels.May ↑ risk of bleeding with warfarin.↓ levels with proton pump inhibitors and H2 blockers ; avoid concurrent use.St. John's wort may ↓ levels and may ↓ response; alternative therapy or ↑ dose should be considered.

Route/Dosage

Oral (Adults) Non–small-cell lung cancer–150 mg daily taken at least 1 hr before or 2 hr after food; Pancreatic cancer—100 mg daily taken at least 1 hr before or 2 hr after food.

Availability

Tablets: 25 mg, 100 mg, 150 mg

Nursing implications

Nursing assessment

  • Assess respiratory status prior to and periodically during therapy. If dyspnea, cough, or fever occur, discontinue erlotinib, assess for interstitial lung disease, and institute treatment as needed.
  • Assess for diarrhea. Usually responds to loperamide but may require dose reduction or discontinuation of therapy if patient becomes dehydrated.
  • Assess skin throughout therapy. If bullous, blistering, and exfoliative skin conditions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, occur, interrupt or discontinue treatment. Skin rash may require treatment with corticosteroids or anti-infectives with anti-inflammatory properties; acne treatments may aggravate dry skin and erythema.
  • Assess eyes periodically during therapy. If acute or worsening eye disorders or pain occur, interrupt or discontinue therapy.
  • Assess for GI pain. Patients receiving concomitant antiangiogenic agents, corticosteroids, NSAIDs, and/or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease, are at increased risk for GI perforation. Permanently discontinue erlotinib in patients who develop gastrointestinal perforation.
  • Lab Test Considerations: Monitor liver function tests (AST, ALT, bilirubin, alkaline phosphatase) periodically during therapy. Dose reduction or discontinuation of therapy should be considered if severe changes in liver function (total bilirubin ≥3 times upper limit of normal and/or transaminases ≥5 times upper limit of normal) occur.
    • Monitor renal function and electrolytes in patients at risk for dehydration. Withhold therapy if dehydration occurs.
    • Monitor INR regularly in patients taking warfarin. May cause ↑ INR.

Potential Nursing Diagnoses

Ineffective breathing pattern (Side Effects)

Implementation

  • Oral: Administer at least 1 hr before or 2 hr after food.

Patient/Family Teaching

  • Instruct patient to take erlotinib as directed.
  • Advise patient to notify health care professional if severe or persistent diarrhea, nausea, anorexia, vomiting, onset or worsening of skin rash, unexplained dyspnea or cough, or eye irritation occur.
  • Advise patient to wear sunscreen and protective clothing to decrease skin reactions.
  • Caution patient to use highly effective contraceptive during and for at least 2 wk after completion of therapy. Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding.
  • Instruct patient to discontinue smoking during therapy; smoking decreases blood levels of erlotinib.

Evaluation/Desired Outcomes

  • Decrease in spread of non–small-cell lung or pancreatic cancer with increased survival.

erlotinib

a miscellaneous antineoplastic.
indication This drug is used in the treatment of non-small cell lung cancer.
contraindications Pregnancy and known hypersensitivity to this drug prohibit its use.
adverse effects A life-threatening side effect of this drug is interstitial lung disease. Common side effects include nausea, diarrhea, vomiting, anorexia, mouth ulceration, rash, conjunctivitis, eye pain, fatigue, infection, cough, and dyspnea.

erlotinib

An epidermal growth factor receptor inhibitor drug that has been shown capable of prolonging survival in patients with non-small-cell lung cancer after one or two prior chemotherapy courses.
References in periodicals archive ?
Norway-based BerGenBio has met the first efficacy endpoint in the phase II clinical trial assessing BGB324 (bemcentinib), a selective AXL inhibitor, in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC) who have progressed on an approved epidermal growth factor receptor (EGFR) inhibitor, it was reported yesterday.
Acquisition of medicines: Erlotinib, Pertuzumab, Trastuzumab emtansina, Vismodegib, Rituxumab and obinutuzumab
Reportedly, the MAAv submission is based on data from the Phase III FLAURA trial, in which Tagrisso significantly improved progression-free survival (PFS) compared to current 1st-line EGFR-TKIs, erlotinib or gefitinib, in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC.
The Phase III JUNIPER study was designed to evaluate the efficacy and safety of abemaciclib versus erlotinib in patients with stage IV NSCLC with a detectable KRAS mutation, who have progressed after platinum-based chemotherapy and who may have received one additional systemic therapy.
So far, chemopreventive agents which have been tested in clinical trials for oral pre-cancer lesions include vitamin A, isotretinoin (13-cis retinoic acid), beta-carotene, cyclooxygenase-2 (COX-2), bowman-brick inhibitor concentration, erlotinib, green tea extract, freeze-dried black raspberry (BRB) and special medicinal herbs.
Data Sources: An electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib, icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.
El presente caso nos muestra a un paciente varon no asiatico y fumador pesado con el diagnostico de adenocarcinoma pulmonar sin clinica respiratoria en estadio clinico IV, que debuto con clinica neurologica por metastasis cerebral y que tuvo buena respuesta al tratamiento con erlotinib.
Erlotinib and Gefitinib are inhibitors of human epidermal growth factor receptor-1 and the epidermal growth factor receptor tyrosine kinase.
3 as a biomarker of intrinsic and acquired resistance to erlotinib in human pancreatic and lung carcinomas irrespective of their KRAS mutational status.
A new study published online ahead of print in the Journal of Thoracic Oncology concludes that Biodesix' VeriStrat test was predictive of survival outcomes between erlotinib and gemcitabine.
The drugs, Erlotinib and Gefitinib, which are in a class of highly-specific small molecule tyrosine kinase inhibitors, work by blocking the activation of EGFR which is involved in cell survival and growth, as well as the development of a nourishing blood supply and metastasis.