Pemetrexed

Pemetrexed is a folic acid antagonist with antitumoral, antiproliferative and cytostatic properties. In a narrower sense, folic acid analogues are a small group of (non-selectively acting) cytostatic drugs (so-called antimetabolites) with methotrexate (MTX) as the lead substance. The effects of pemetrexed are based on the inhibition of folate-dependent metabolic processes that are important for cell division. Pemetrexed inhibits the folate-dependent enzymes:

• Thymidylate synthase
• dihydrofolate reductase and
• Glycinamide ribonucleotide formyltransferase.

These enzymes are involved in the biosynthesis of pyrimidine and purine nucleotides. These are components of DNA and RNA that are required for these. The half-life of pemetrexed is about 3.5 hours.

Malignant pleural mesothelioma (C45.0).

In combination with cisplatin for the treatment of chemonaive patients with unresectable malignant pleural mesothelioma.

Non-small cell lung cancer (NSCLC - C34.9).

Pemetrexed is indicated in combination with cisplatin for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (C34.9)

Monotherapy: In patients with non-small cell lung cancer after prior chemotherapy, the recommended dose of pemetrexed is 500 mg/m² KOF administered as an intravenous infusion over a 10-minute period on the first day of each 21-day treatment cycle.

Note: Premedication: To reduce the frequency and severity of skin reactions, a glucocorticoid(e.g., 2x 4 mg dexamethasone p.o.) must be given the day before and the day of pemetrexed administration and the day after treatment.

General ADRs:

• General tendency to infection
• Fatigue (tiredness)
• Fever
• Oedema tendency

UAW of the mucous membranes

• Pharyngitis
• Stomatitis
• ulcers of the mucous membranes

Hematological UAW

• Neutropenia
• Thrombocytopenia
• Anemia

Gastrointestinal UAW

• Oesophagitis
• Loss of appetite
• Vomiting
• Diarrhoea
• Nausea
• Colitis

Dermatological UAW:

• Erythema
• Hyperpigmentation of the skin
• Pruritus
• Erythema multiforme
• Urticaria
• Ophthalmologic ADR
• Drought,
• Conjunctivitis

Cardiological UAW

• Heart Failure
• Arrhythmias

Hepatological UAW

• Pathological liver serology

Nephrological UAW

• Renal insufficiency

Raltitrexed®

1. Adjei A.A (2004) Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent. Clin Cancer Res 10: 4276s-4280s

2. Curtin NJ et al (2001) Pemetrexed disodium, a novel antifolate with multiple targets. Lancet Oncol 2: 298-306

3. Ramalingam SS et al (2019) Pemetrexed, Bevacizumab, or the Combination As Maintenance Therapy for Advanced Nonsquamous Non-Small-Cell Lung Cancer: ECOG-ACRIN 5508 J Clin Oncol 37(:2360-2367