Cancer Terms Explained

DPD Deficiency

Having a deficiency in the DPD enzyme could make the side effects of certain chemotherapy drugs worse. For some people, these side effects can be life threatening. This group of drugs are called fluoropyrimidines. Examples include 5-fluorouracil (5FU) and capecitabine. What is DPD deficiency? DPD stands for dihydropyrimidine dehydrogenase. It is an enzyme the liver makes that helps the body break down thymine and uracil. Thymine and uracil make up part of the structure of our genes. Uracil is also an important part of the drugs 5FU and capecitabine. DPD deficiency happens when we have low or no levels of the DPD enzyme. The cause of this is usually changes (mutations) in the DPYD gene. It is very rare to have no DPD in the body (a complete DPD deficiency), but it is more common to have low or very low levels (a partial deficiency). Between 2 and 8 out of every 100 people (2 to 8%) have a partial DPD deficiency. A partial DPD deficiency doesn't usually cause symptoms. This means you don't usually know that you have the deficiency unless you have 5FU or capecitabine. People with severe or complete DPD deficiency usually start to have symptoms as babies. They might have: fits (seizures)a small head size (microcephaly)problems with their development, such as walking and talkingDPD deficiency and the side effects of capecitabine and 5FU The DPD enzyme helps our body to break down fluorouracil (5FU) and capecitabine (also known as Xeloda). Fluorouracil (5FU) and capecitabine are two common chemotherapy drugs. They are used as a treatment for several different cancers, including: breastbowelhead and neckstomachback passage (anus)bile ductpancreasneuroendocrine tumours or neoplasmsWithout enough DPD enzyme, these chemotherapy drugs build up in the body and cause more severe side effects than usual. In some situations, these side effects can be life threatening. The side effects include: a drop in the level of blood cells increasing your risk of infections, breathlessness, and bleedingdiarrhoea which can be severe a sore mouthfeeling or being sick which can cause dehydration soreness, redness and peeling on palms and soles of feetBetween 20 and 30 out of every 100 people (20 and 30%) have severe side effects from 5FU and capecitabine. Less than 1 in every 100 people (less than 1%) who have 5FU and capecitabine die from their treatment. But not everyone has a DPD deficiency. So, it is important to speak with your doctor about your side effects.  So far, research has shown that people with DPD deficiency usually develop severe side effects to 5FU or capecitabine within the first 2 treatment cycles.  Is there a test to check for DPD deficiency? All people having 5FU or capecitabine should have a blood test before their treatment to check if they have a DPD deficiency. Research into DPD deficiency testing Doctors and scientists are looking at learning more about DPYD. Research looking into the DPYD gene Researchers are looking into using genetic information to help personalise chemotherapy. They are looking at the dose of chemotherapy and how to reduce common side effects. In the study, they will collect genetic information. In this study, they look at how the differences in our genes can affect our unique response to medications. The study includes looking at the DPYD gene.

Folinic Acid, Fluorouracil And Irinotecan (FOLFIRI)

FOLFIRI is the name of a chemotherapy combination that includes: folinic acid (also called leucovorin, calcium folinate or FA)fluorouracil (also called 5FU)irinotecanFOLFIRI is also known as irinotecan de Gramont or irinotecan modified de Gramont. It is a treatment for advanced bowel cancer and other digestive (gastric) cancers. How it works These cancer drugs destroy quickly dividing cells, such as cancer cells. How you have FOLFIRI You might have treatment through a long plastic tube that goes into a large vein in your chest. The tube stays in place throughout the course of treatment. This can be a: central linePICC lineportacath You have the fluorouracil (5FU) through a small pump. The pump slowly puts the fluid into your bloodstream (infusion). You can keep the pump in a small bag or attach it to a belt. You'll need to go back to the hospital after the second day of your treatment to have the pump removed. Or sometimes a chemotherapy nurse may be able to do it for you at home. If you don't have a central line You might have treatment through a thin short tube (a cannula) that goes into a vein in your arm. You have a new cannula each time you have treatment. You usually stay in hospital as an inpatient if you have FOLFIRI through a cannula. When you have FOLFIRI You have FOLFIRI chemotherapy as cycles of treatment. This means that you have the drug and then a rest to allow your body to recover. Each cycle of treatment lasts 2 weeks (14 days). Depending on your needs, you may have up to 12 cycles, taking up to 6 months in total. Exactly how you have your drugs may depend your treatment centre and your circumstances. The following is an example: Day 1You have irinotecan through a drip into the bloodstream over 30 to 90 minutes (depending on which cycle you are having).You have folinic acid through a drip into the bloodstream over 2 hours.You have an injection of fluorouracil into the bloodstream over 5 minutes.You have an infusion of 5FU through a drip or pump into the bloodstream for 46 hours. Day 2You continue to have the 5FU infusion. Day 3The pump is disconnected. Then you start the cycle again. Tests You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver and kidneys are working. Side effects How often and how severe the side effects are can vary from person to person. They also depend on what other treatment you are having.  When to contact your team Your doctor, pharmacist or nurse will go through the possible side effects. They will monitor you closely during treatment and check how you are at your appointments. Contact your advice line as soon as possible if: you have severe side effects your side effects aren't getting any betteryour side effects are getting worsethe side effects are affecting your daily lifeEarly treatment can help manage side effects better.  Contact your advice line, doctor or nurse immediately if you have signs of infection, such as a temperature above 37.5C or below 36C, or if you develop a severe skin reaction. Signs of a severe skin reaction include peeling or blistering of the skin. We haven't listed all the side effects here. Remember it is very unlikely that you will have all of these side effects, but you might have some of them at the same time. Common side effects These side effects happen in more than 10 in 100 people (more than 10%). You might have one or more of them. They include: Increased risk of infection Increased risk of getting an infection is due to a drop in white blood cells. Symptoms include a change in temperature, aching muscles, headaches, feeling cold and shivery and generally unwell. You might have other symptoms depending on where the infection is. Infections can sometimes be life threatening. You should contact your advice line urgently if you think you have an infection.  Bruising, bleeding gums or nose bleeds This is due to a drop in the number of platelets in your blood. These blood cells help the blood to clot when we cut ourselves. You may have nosebleeds or bleeding gums after brushing your teeth. Or you may have lots of tiny red spots or bruises on your arms or legs (known as petechiae). Breathlessness and looking pale You might be breathless and look pale due to a drop in red blood cells. This is called anaemia. Inflammation of the mouth, throat, food pipe and back passage It may be painful to swallow drinks or food. Painkillers and mouth washes can help to reduce the soreness and keep your mouth healthy. Other parts of the digestive system can also be affected. An inflamed food pipe (oesophagus) can cause heartburn. Inflammation of the back passage (rectum) can cause diarrhoea. Other symptoms are pain, bleeding and discharge and the feeling that you want to pass a bowel movement. Speak to your doctor or nurse if you have these symptoms. Feeling or being sick Feeling or being sick is usually well controlled with anti sickness medicines. Avoiding fatty or fried foods, try eating small meals and snacks, drinking plenty of water, and relaxation techniques can all help. It is important to take anti sickness medicines as prescribed even if you don't feel sick. It is easier to prevent sickness rather than treat it once it has started. Diarrhoea Contact your advice line if you have diarrhoea, such as if you've had 4 or more loose watery poos (stools) in 24 hours. Or if you can't drink to replace the lost fluid. Or if it carries on for more than 3 days. Your doctor may give you anti diarrhoea medicine to take home with you after treatment. Eat less fibre, avoid raw fruits, fruit juice, cereals and vegetables, and drink plenty to replace the fluid lost. Acute cholinergic syndrome Irinotecan can cause some people to develop a set of side effects during or within the first 24 hours after having the drug. These side effects include diarrhoea (which may be severe), sweating, stomach cramps, increased production of saliva, and watery eyes. You may have an injection of atropine before the irinotecan to reduce these side effects. Diarrhoea can be severe. Contact your treatment centre straight away if you have diarrhoea within 24 hours of having irinotecan. You'll need to have treatment. Difficulty breathing You may have difficulty breathing with wheezing and coughing. Let your healthcare team know straight away if this happens.  Raised uric acid levels in the blood High levels of uric acid in your blood can lead to a build up of crystals in body tissues and cause inflamed joints. You'll have regular blood tests to check your levels. Drinking plenty of fluids helps to flush out the excess uric acid. You might also have medicines to control the uric acid levels. Changes in your heart rhythm These drugs can cause changes to your heart rhythm. So before you start treatment you might have tests to check your heart, such as an electrocardiogram (ECG). Less commonly the drugs can cause chest pain. Rarely they can cause other problems to do with your heart such as a heart attack. Loss of appetite You might lose your appetite for various reasons while having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks. Hair loss You could lose all your hair. This includes your eyelashes, eyebrows, underarms, legs and sometimes pubic hair. Your hair will usually grow back once treatment has finished but it is likely to be softer. It may grow back a different colour or be curlier than before.  Soreness, redness and peeling on palms and soles of feet The skin on your hands and feet may become sore, red, or may peel. You may also have tingling, numbness, pain and dryness. This is called hand-foot syndrome or palmar plantar syndrome. Moisturise your skin regularly. Your healthcare team will tell you what moisturiser to use. Slow wound healing Any wounds you might have can take longer to heal. Keep wounds clean to prevent infection. Contact your GP or specialist nurse if you are worried about a wound. Tiredness and weakness You might feel very tired and as though you lack energy. Various things can help you to reduce tiredness and cope with it, for example exercise. Some research has shown that taking gentle exercise can give you more energy. It is important to balance exercise with resting. Liver changes You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes. You have regular blood tests to check for any changes in the way your liver is working. 5FU can cause liver cell damage, but this is rare. Occasional side effects These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%). You might have one or more of them. They include: chest painconstipationhigh temperature (fever)tummy (abdominal) painRare side effects This side effects happens in fewer than 1 in 100 people (fewer than 1%). You might have one or more of them. They include: a reaction during the infusion – you might get a rash, shortness of breath, redness or swelling of the face and dizziness – tell your team straight away if this happensblood clots that are life threatening; signs are pain, swelling and redness where the clot is. Feeling breathless can be a sign of a blood clot on the lung. Contact your advice line or doctor straight away if you have any of these symptomsdifficulty sleeping (insomnia) or feeling sleepymood changes such as feeling agitated, depressed or feeling very happy (euphoria)having epileptic seizures (fits) more often if you have epilepsyraised levels of thyroid hormonesfeeling confused and disorientated, and having problems with walking or speaking due to changes in the braineye problems including eyes moving quickly from side to side (nystagmus), inflammation, blocked tear ducts, blurred vision, eyelid turning outwards, watery eyes and double visionheadachesshaking and trembling, stiffness and slow movement (symptoms of Parkinson's disease)an increase in the muscle tone of your legs and feet causing them to be stifflow blood pressurea lack of blood flow to the brain, bowel, arms, legs and skinloss of body fluid (dehydration)bleeding and ulcers in the digestive systemskin problems such as rash, dry skin, increased sensitivity to sunlight, hives, darkening of the skinnail problems such as thickening, inflammation, pain, changes in colour of the nail and nail beddizzinessinflammation of the gall bladder and damage to the bile ductsOther side effects There isn't enough information to work out how often these side effects might happen. You might have one or more of them. They include: raised levels of ammonia in the bloodinflammation of the lining around your heartWhat else do I need to know? Other medicines, food drink Cancer drugs can interact with some other medicines and herbal products. Tell your doctor or pharmacist about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies. Phenytoin Fluorouracil can raise the levels of phenytoin in your blood. You should have regular blood tests to prevent this from happening. Sodium This drug contains sodium (salt). You might need to take account of this if you are on a controlled sodium diet. Tell your doctor if you are on a low salt diet. Loss of fertility You may not be able to become pregnant or get someone pregnant after treatment with these drugs. Talk to your doctor before starting treatment if you think you may want to have a baby in the future. Men might be able to store sperm before starting treatment. And women might be able to store eggs or ovarian tissue. But these services are not available in every hospital, so you would need to ask your doctor about this.     Pregnancy and contraception This treatment may harm a baby developing in the womb. It is important not to become pregnant or get someone pregnant while you're having treatment and for at least 6 months afterwards. Talk to your doctor or nurse about effective contraception before starting treatment. Let them know straight away if you or your partner falls pregnant while having treatment. Breastfeeding It is not known whether this drug comes through into the breast milk. Doctors usually advise that you don't breastfeed during this treatment. Low levels of DPD Between 2 and 8 out of 100 people (2 to 8%) have low levels of an enzyme called dihydropyrimidine dehydrogenase (DPD) in their bodies. A lack of DPD can mean you're more likely to have severe side effects from capecitabine or fluorouracil. It might take you a bit longer to recover from the chemotherapy. These side effects can rarely be life threatening. Before starting treatment with capecitabine or fluorouracil you have a blood test to check levels of DPD. So you may start treatment with a lower amount (dose) of the drug or have a different treatment. Your doctor or nurse will talk to you about this. Treatment for other conditions Always tell other doctors, nurses, pharmacists or dentists that you're having this treatment. For example, if you need treatment for anything else, including teeth problems. Immunisations Don't have immunisations with live vaccines while you're having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having. Ask your doctor or pharmacist how long you should avoid live vaccinations. In the UK, live vaccines include rubella, mumps, measles, BCG, yellow fever and one of the shingles vaccines called Zostavax. You can have: other vaccines, but they might not give you as much protection as usual the flu vaccine (as an injection) the coronavirus (COVID-19) vaccine - talk to your doctor or pharmacist about the best time to have it in relation to your cancer treatment Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine. This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system recovers from treatment. Contact with others who have had immunisations - You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If this happens they should keep the area covered. If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray as this is a live vaccine. This is for 2 weeks following their vaccination. Babies have the live rotavirus vaccine. The virus is in the baby's poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn't possible, wash your hands well after changing their nappy. More information about this treatment For further information about this treatment go to the electronic Medicines Compendium (eMC) website. You can report any side effect you have to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme. This page is due for review. We will update this as soon as possible.

Chemotherapy Shortages Trouble Study Investigators

Roby Thomas, MD discusses chemotherapy shortages and the impact these shortages have had on oncology research.

Roby Thomas, MD, a medical oncologist, and hematologist at UPMC Hillman Cancer Center, discusses chemotherapy shortages and the impact these shortages have had on oncology research.

Thomas explains that an important agent for the treatment of gastrointestinal and genitourinary oncology is nab-paclitaxel. The chemotherapeutic is standard treatment for pancreatic cancer, breast cancer, and non–small cell lung cancer. Nab-paclitaxel is also being investigated in studies of patients with gastric cancer, and breast cancer with brain metastases. Thomas explains that continuing these studies was a big challenge back when there was a shortage of nab-paclitaxel

Many oncologists used the combination of leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) in place of nab-paclitaxel, says Thomas. FOLFIRINOX is the only alternative treatment for these patients, but for older patients, it may be too toxic.

Other necessary agents include gemcitabine and cisplatin, which are currently short of supply.

0:08We've had multiple issues with drug shortages over the last couple of years, primarily because of supply chain issues. In the fields that I focus on, gastrointestinal and genitourinary oncology, we had a shortage of nab-paclitaxel for quite some time, and that was in the United States. What made it so challenging is we use that drug often in pancreatic cancers. At UPMC Hillman Cancer Center, we have a high volume of pancreatic cancers, and it's 1 of our standard-of-care therapies.

0:51What made it uniquely challenging for us was that we have many different phase 1 and phase 2 clinical trials in which nab-paclitaxel would be part of a standard-of-care regimen. People might be randomized to get gemcitabine and nab-paclitaxel with or without another study drug or placebo, for example, but we couldn't recruit people because we just didn't have the study medication. It did not just have a direct effect in terms of less nab-paclitaxel availability, but also in terms of accrual and clinical trials. It was a challenging time for pancreatic cancer in general.

---