Pemetrex
Generic Name:Pemetrexed
Indications
Pemetrex is indicated in Non-Squamous Non-Small Cell Lung Cancer (NSCLC):
- in combination with Pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous NSCLC, with no EGFR or ALK genomic tumor aberrations.
- in combination with Cisplatin for the initial treatment of patients with locally advanced or metastatic, nonsquamous, non-small cell lung cancer (NSCLC).
- as a single agent for the maintenance treatment of patients with locally advanced or metastatic, nonsquamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
- as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy.
Limitations of Use: Pemetrex is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer.
Mesothelioma: Pemetrex is indicated, in combination with Cisplatin, for the initial treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.
Pharmacology
Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. In vitro studies show that Pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, Pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of of TS and GARFT.
Dosage
Recommended Dosage for Non-Squamous NSCLC: The recommended dose of Pemetrexed when administered with Pembrolizumab and platinum chemotherapy for the initial treatment of metastatic non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 as an intravenous infusion over 10 minutes administered after Pembrolizumab and prior to Carboplatin or Cisplatin on Day 1 of each 21-day cycle for 4 cycles. Following completion of platinum-based therapy, treatment with Pemetrexed with or without Pembrolizumab is administered until disease progression or unacceptable toxicity.
The recommended dose of Pemetrexed when administered with Cisplatin: for initial treatment of locally advanced or metastatic non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 as an intravenous infusion over 10 minutes administered prior to Cisplatin on Day 1 of each 21-day cycle for up to six cycles in the absence of disease progression or unacceptable toxicity.
The recommended dose of Pemetrexed for maintenance treatment of non-squamous NSCLC: in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity after four cycles of platinum-based first-line chemotherapy.
The recommended dose of Pemetrexed for treatment of recurrent non-squamous NSCLC: in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
Recommended Dosage for Mesothelioma: The recommended dose of Pemetrexed when administered with Cisplatin in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
