3 Clinical need and practice
3.1 The purpose of this assessment is to evaluate the clinical and cost effectiveness of the My5‑FU assay for the pharmacokinetic dose adjustment of continuous infusion 5‑fluorouracil (5‑FU) chemotherapy.
3.2 Pharmacokinetic dose adjustment of 5‑FU may result in increased overall and progression-free survival, by increasing the number of people having an optimum therapeutic dose of 5‑FU and by reducing the incidence of side effects and toxicities. Commonly reported side effects of 5‑FU chemotherapy include diarrhoea, oral and gastrointestinal mucositis, anaemia, fatigue, nausea and vomiting, and palmar‑plantar erythrodysesthesia (hand‑foot syndrome), all of which, when severe, can indicate the need to limit the dose. In severe cases, 5‑FU toxicity can lead to neuropathy (damage to nerve cells), severe damage to organs, cardiotoxicity, neutropenia, sepsis and septic shock. In addition, people with DPD (dihydropyrimidine dehydrogenase) deficiency have a reduced ability to metabolise 5‑FU and can develop serious toxicity following treatment.
3.3 Continuous infusion 5‑FU chemotherapy is commonly used in the treatment of many cancers including colorectal, head and neck, stomach and pancreatic cancer.
3.4 Colorectal cancer describes cancers originating in the colon or rectum, and is the fourth most common cancer in the UK with around 40,000 new cases registered each year. Around half of all people diagnosed with colorectal cancer survive for at least 5 years after diagnosis.
3.5 Head and neck cancer describes a variety of malignant tumours occurring in the head and neck region, mainly in the mouth and throat. Around 16,000 people in the UK are diagnosed with a head and neck cancer each year. Five‑year survival rates vary depending on the type of head and neck cancer; thyroid cancer has an estimated 5‑year survival rate of 87%, whereas the 5‑year survival rate for hypopharyngeal cancer is 26%.
3.6 Stomach cancer is the ninth most common cancer in males in the UK and the fourteenth most common in females. Around 42% of people will survive for a year after diagnosis, although this falls to around 18% after 5 years.
3.7 Pancreatic cancer is the tenth most common cancer in the UK and the fifth most common cause of death from cancer. Pancreatic cancer has a poor survival rate because of typical late presentation and early metastases. It is estimated that less than a fifth of patients present with potentially curable tumours and the overall 5‑year survival rate is less than 5%.
3.8 5‑FU chemotherapy is used in the treatment of many different cancers and it can be given intravenously (by injection or as an infusion) or orally. 5‑FU can be prescribed as a single agent or as a regimen, in conjunction with other chemotherapy drugs. 5‑FU is commonly administered alongside folinic acid with either oxaliplatin (FOLFOX regimen), or irinotecan (FOLFIRI regimen). An oral version of 5‑FU known as capecitabine is sometimes used instead of intravenous 5‑FU and this is also often administered alongside oxaliplatin and irinotecan. Capecitabine is a prodrug of 5‑FU, that is, an inactive form of 5‑FU that is converted into active 5‑FU in the tumour by metabolic processes. This guidance focuses on the pharmacokinetic dose adjustment of continuous infusion 5‑FU only.
3.9 Chemotherapy is usually given as a course of treatments over 3–6 months. An average course of chemotherapy typically includes between 4 and 8 cycles. Continuous infusions of 5‑FU last for around 22–48 hours and usually require a patient to have a central venous access device (such as a central line or peripherally inserted central catheter). Some patients are able to have their 5‑FU infusion through a portable pump that can make it possible for them to go home during treatment.
3.10 NICE has developed care pathways that include the use of 5‑FU in clinical practice. 5‑FU is commonly given to people with a confirmed diagnosis of: colorectal cancer, head and neck cancer, stomach cancer or pancreatic cancer.