gefitinib

gefitinib

COMMON TRADE NAME(S):   Iressa®

• Non-small cell lung cancer

Refer to the product monograph for a full list and details of approved indications.

• Head and neck cancer

Emetogenic Potential:  

Extravasation Potential:   Not applicable

The following table contains adverse effects reported from the IPASS trial for the 250mg daily dose.

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

Gefitinib was generally well-tolerated, with the most commonly reported effects being gastrointestinal (diarrhea, nausea and vomiting) and skin changes (rash, acne, dry skin, and pruritus).

Skin reactions (acneiform rash on face, scalp or chest) are common and usually mild to moderate, but may be severe.  They usually appear by day 10 to 14 of treatment, may diminish with continued treatment, and are reversible when drug is withdrawn. In some patients the rash may be itchy or painful, cosmetically worrisome or associated with paronychiae, and usually be managed with a brief interruption of therapy.

Diarrhea is another frequently occurring adverse event; 1% of patients have grade 3 or 4 diarrhea, which may be associated with dehydration and should be managed appropriately. Problematic symptoms can also be managed by providing a brief therapy interruption.

Renal failure has been observed and is secondary to dehydration due to diarrhea, nausea/vomiting, anorexia, concurrent infections, or concurrent medications (e.g. chemotherapy).

Interstitial Lung Disease has been reported in 1% of patients receiving gefitinib, and may be fatal in up to a third of the cases.  The reported incidence appears higher in Japan.  The incidence may increase in patients with pre-existing ILD, a recent diagnosis of NSCLC (< 6 months) with poor PS, with concurrent heart disease, who are ≥ 55 years or are current smokers.  If patients present with worsening of respiratory symptoms such as dyspnea, cough and fever, gefitinib should be interrupted and prompt investigation initiated.

Hemorrhages have been reported in 4% of patients but may be fatal, and usually involve gastrointestinal or respiratory systems.  Rare, fatal cases of gastrointestinal perforation have been reported in patients with risk factors such as concomitant NSAIDs or steroids, history of GI ulcer, age, smoking, GI obstruction, advanced bowel disease and bowel metastases at perforation sites.

Corneal erosion is uncommon with gefitinib use and is reversible. Other generally mild ophthalmic symptoms such as conjunctivitis, blepharitis, abnormal eyelash growth and dry eye are commonly reported. Recent corneal surgery and contact lens wearing are independent risk factors for ocular toxicity.  Patients should be instructed to seek medical attention promptly if any eye symptoms develop.

• in patients with severe hypersensitivity to gefitinib or to any of its excipients
• EGFR mutation negative tumours
   

• contains lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
• risk of mortality among patients who develop ILD is higher in patients who are smokers, have pre-existing ILD, ≥ 65 years old, or have extensive areas adherent to the pleura.

• Carcinogenicity: Yes
  Gefitinib has potential phototoxic and contact sensitizing effects.

• Genotoxicity: No
  
• Crosses placental barrier: Yes
  
• Fetotoxicity: Yes
  
• Pregnancy:

  Gefitinib is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 6 months after the last dose. (general recommendation)

• Excretion into breast milk: Yes
  
• Breastfeeding:

  Breastfeeding is not recommended during treatment.

• Fertility effects: Probable
  

  Documented in studies in female animals.

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
 

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Exceptional Access Program (EAP Website)

• gefitinib - First-line monotherapy in locally advanced (not amenable to curative therapy) or metastatic NSCLC patients who have activating mutations of EGFR-TK, with specific criteria ()

Baselga J, Averbuch SD. ZD1839 (Iressa) as an anticancer agent. Drugs 2000;60 Suppl 1:33-40.

Culy CR, Faulds D. Gefitinib. Drugs 2002;62(15):2237-2248.

Kris MG, Natale RB, Herbst RS et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003;290(16):2149-58.

Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361(10):947-57.

Product Monograph: Iressa® (Gefitinib). AstraZeneca Canada. September 27, 2012.

Shepherd FA, Rodrigues Pereira J, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353(2):123-32.

Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005;366:1527–37.

March 2025 Updated Pregnancy and Lactation section