Pemetrexed

UK SPC (Alimta 100mg powder for concentrate for solution for infusion, https://www.medicines.org.uk/emc/product/3862/smpc). Must only be administered under the supervision of a physician qualified in the use of anti-cancer chemotherapy. IN COMBINATION WITH CISPLATIN: pemetrexed 500 mg/m2 IV over 10 minutes on day 1 of each 21-day cycle, followed by cisplatin 75 mg/m2 infused over two hours approximately 30 minutes after completion of the pemetrexed infusion on day 1 of each 21-day cycle; adequate anti-emetic treatment and appropriate hydration are required before and/or after cisplatin. AS SINGLE AGENT: same 500 mg/m2 dose and schedule in patients treated for non-small cell lung cancer after prior chemotherapy. MANDATORY PRE-MEDICATION AND SUPPLEMENTATION: a corticosteroid equivalent to dexamethasone 4 mg orally twice a day on the day before, the day of, and the day after pemetrexed administration (to reduce skin reactions); oral folic acid or a multivitamin containing folic acid 350 to 1000 micrograms daily, with at least five doses taken during the seven days preceding the first pemetrexed dose, continuing throughout therapy and for 21 days after the last dose; vitamin B12 1000 micrograms by intramuscular injection in the week preceding the first dose and once every three cycles thereafter (subsequent injections may be given on the same day as pemetrexed). MONITORING BEFORE EACH CYCLE: full blood count with differential white cell and platelet count, plus renal and hepatic blood chemistry. Required before starting any cycle: absolute neutrophil count >=1500 cells/mm3, platelets >=100,000 cells/mm3, creatinine clearance >=45 ml/min, total bilirubin <=1.5x upper limit of normal (ULN), and alkaline phosphatase, AST and ALT <=3x ULN (<=5x ULN acceptable if the liver has tumour involvement). DOSE ADJUSTMENTS (apply to both single agent and combination use, based on nadir counts or maximum non-haematologic toxicity in the preceding cycle): nadir ANC <500/mm3 with nadir platelets >=50,000/mm3, or nadir platelets <50,000/mm3 regardless of ANC - 75% of previous dose (both pemetrexed and cisplatin); nadir platelets <50,000/mm3 with bleeding - 50% of previous dose (both drugs). Non-haematologic toxicity Grade >=3 (excluding neurotoxicity): withhold until resolution to <= the patient's pre-therapy value, then any Grade 3 or 4 toxicity except mucositis, or diarrhoea requiring hospitalisation or Grade 3-4 diarrhoea - 75% of previous dose; Grade 3 or 4 mucositis - pemetrexed 50% of previous dose (cisplatin 100%). Neurotoxicity: CTC Grade 0-1 - 100% of previous dose of both; Grade 2 - pemetrexed 100%, cisplatin 50%; discontinue therapy if Grade 3 or 4 neurotoxicity is observed. Discontinue if any haematologic or non-haematologic Grade 3 or 4 toxicity occurs after 2 dose reductions, or immediately for Grade 3-4 neurotoxicity. Elderly: no dose reductions other than those recommended for all patients. Hepatic impairment: no relationship between AST, ALT or bilirubin and pemetrexed pharmacokinetics identified, but patients with bilirubin >1.5x ULN and/or aminotransferase >3.0x ULN (no hepatic metastases) or >5.0x ULN (hepatic metastases present) have not been specifically studied. PAEDIATRIC: there is no relevant use of pemetrexed in the paediatric population in malignant pleural mesothelioma and non-small cell lung cancer (UK SPC); US labelling states safety and effectiveness in paediatric patients have not been established. Any under-18 use must be verified against a children's formulary and specialist paediatric oncology protocol. US labelling additionally describes pemetrexed 500 mg/m2 IV over 10 minutes on Day 1 of each 21-day cycle given with pembrolizumab and platinum chemotherapy for initial treatment of metastatic non-squamous NSCLC (4 cycles) - this combination is not in the fetched UK SPC posology; verify before use.