ERLOCIP 25

Indications

• Locally advanced non-small cell lung cancer after failure of previous chemotherapy
• Metastatic non-small cell lung cancer as monotherapy for maintenance treatment
• Metastatic pancreatic cancer in combination with gemcitabine

Dosage

Children: Refer to B

Adults: 100 mg once daily

Mechanism of action

Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). This inhibition interferes with the signaling pathways that promote cell division and survival, leading to reduced tumor growth and prolonged survival in patients with advanced or metastatic non-small cell lung cancer. Although the exact antitumor mechanism is not fully characterized, erlotinib's specificity for EGFR suggests its role in targeting cancer cells expressing this receptor.

Pharmacodynamics

Erlotinib is a potent inhibitor of the EGFR tyrosine kinase, which plays a critical role in cell signaling, proliferation, and survival. By blocking this pathway, erlotinib induces apoptosis in cancer cells and inhibits tumor growth. Studies indicate that erlotinib may also exert immunosuppressive effects on T lymphocytes, inhibiting their proliferation and activation in a concentration-dependent manner.

Pharmacokinetics

Erlotinib is well absorbed after oral administration, with peak plasma concentrations typically reached within 4 to 8 hours. It is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, particularly CYP3A4. The drug has a half-life of approximately 36 hours, allowing for once-daily dosing. Its pharmacokinetics can be influenced by concurrent medications and food, necessitating caution in drug interactions. Dosage adjustments may be required in the presence of potent CYP3A4 inhibitors or inducers.

Adverse effects

• Peripheral swelling
• Photosensitivity
• Abnormal skin reactions
• Sleep disorders
• Syncope
• Taste disturbances
• Diarrhoea
• Eye inflammation
• Brittle nails
• Increased risk of infection
• Keratitis
• Ulcerative keratitis

Interactions

• Cobicistat: Moderate (increases exposure)
• Combined hormonal contraceptives: Moderate (increases exposure)
• Idelalisib: Moderate (increases exposure)
• Mexiletine: Moderate (increases exposure)
• Osilodrostat: Moderate (increases exposure)
• Rucaparib: Moderate (increases exposure)
• SSRIs: Moderate (increases exposure)
• Vemurafenib: Moderate (increases exposure)
• Clarithromycin: Moderate (increases exposure)
• Ciprofloxacin: Moderate (increases exposure)

Precautions

• Patients should be monitored for signs of keratitis and ulcerative keratitis
• Caution advised regarding driving and skilled tasks due to potential cognitive disorders
• Patients of childbearing potential should use effective contraception during treatment and for specified durations post-treatment

Pregnancy

Manufacturer advises to avoid due to limited information available.

Breast-feeding

Manufacturer advises to avoid due to no information available.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets: 100 mg

Mechanism of action

The mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells. Although the exact mechanism of antineoplastic activity of erlotinib has not been fully elucidated, erlotinib appears to inhibit the intracellular phosphorylation of tyrosine kinase associated with EGFR, which is expressed on the surface of normal and cancer cells. Specificity with regard to other tyrosine kinase receptors has not been fully characterized. Erlotinib is a potent inhibitor of epidermal growth factor receptor tyrosine kinase and has been demonstrated to treat advanced or metastatic non-small cell lung cancer to prolong survival after failure of first-line or second-line chemotherapy. However, little is known about its effects on immune system. In the present study, /investigators/ aimed to investigate the immunosuppressive activity of erlotinib on T lymphocytes both in vitro and in vivo, and further explore its potential molecular mechanism. Erlotinib exerted a significant inhibition on the T cell proliferation and activation induced by concanavalin A, anti-CD3 plus anti-CD28, staphylococcal enterotoxin B or phorbol myristate acetate respectively in a concentration-dependent manner and it also inhibited the secretion of the proinflammatory cytokines such as IL-2 and IFN-gamma of activated T cells. Further study showed that erlotinib caused G0/G1 arrest and suppressed the phosphorylations of c-Raf, ERK and Akt in activated T cells. Moreover, erlotinib significantly ameliorated picryl chloride-induced ear contact dermatitis in a dose-dependent manner in vivo. In summary, these findings suggest that erlotinib may cause the impairment of T-cell-mediated immune response both in vitro and in vivo through inhibiting T cell proliferation and activation, which is closely associated with its potent down-regulation of the c-Raf/ERK cascade and Akt signaling pathway.