Coping with ROS1 TKI Side Effects

The side effects of a ROS1 targeted therapy tyrsoine kinase inhibitor (TKI) can be a challenge. Coping successfully with these side effects is critical to staying on the TKI as long as possible.
We hope these tips from ROS1ders' personal experiences will help you maintain good quality of life while you are taking a ROS TKI.

 
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Overview

Targeted therapy drugs, or “TKIs” (​​tyrosine kinase inhibitors), are frequently prescribed to patients with ROS1+ cancer. As cancer treatments go, TKIs are often quite tolerable. Still, many patients experience side effects.  

Dealing with side effects is a frequent topic of conversation in The ROS1ders private Facebook group. We’ve assembled some of our community’s best tips for handling common TKI side effects below.  Some are recommendations we've received from ROS1 Clinician-Researchers, others come from other health professionals or other trusted sources.  The tips focus on side effects associated with three ROS1 TKIs --crizotinib, entrectinib and lorlatinib -- with which our group has had the most experience. 

This list of side effects is not exhaustive.  We've included links to the manufacturers’ website for each TKI, which has a more complete description of some side effects. 

Don't let this long list of potential side effects scare you!  The important thing to remember is that the vast majority of cancer patients find TKIs give them a better quality of life than they would have on chemotherapy.  

 

Each patient and their treatment experience is unique. Some people have no side effects, while others have many. Some side effects show up at the beginning of treatment and go away over time, whereas others worsen over time. Our suggestions may work well for some patients, but not for others.

Please consult your medical team before making critical treatment decisions.  Importantly, you should never lower the dosage of your TKI, change your TKI dosing schedule,  or stop taking your TKI without first consulting your medical team. 

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About Commonly Prescribed ROS1 TKIs

 

Crizotinib (brand name Xalkori) was the first TKI used for ROS1+ cancer. It received accelerated approval from the US FDA in 2016 for treating ROS1+ non-small cell lung cancer (NSCLC). Therefore, ROS1+ patients have a great deal of collective experience managing Xalkori’s side effects. The onboarding dose is usually 250 mg twice daily, though it is not uncommon to have doses reduced to manage side effects. 

Entrectinib (brand name Rozlytrek) is typically prescribed as a first-line TKI but may also be used as a second-line treatment in some cases. It received accelerated approval from the FDA in 2019 for treating ROS1+ NSCLC. It effectively treats the brain (unlike crizotinib) so it is often prescribed first line for patients who have brain metastases. The onboarding dose is usually 600 mg daily, though it is not uncommon to have doses reduced to manage side effects. 

Lorlatinib (brand name Lobrena) is a TKI that can work for some ROS1ders after other drugs are no longer effective. Lorlatinib is able to penetrate the blood-brain barrier, so it is often effective against brain metastasis. It has received accelerated FDA approval for  ALK+ non-small cell lung cancer, but is not approved for ROS1+ cancer. However, it is recommended by the National Comprehensive Cancer Network for second- and third-line treatment of ROS1+ non-small cell lung cancer. U.S. based ROS1+ NSCLC patients can acquire this TKI “off label” (usually covered by insurance). Some patients have acquired lorlatinib through a clinical trial or compassionate use. The onboarding dose is usually 100 mg daily, though it is not uncommon to have doses reduced to manage side effects (some patients experience neurologic or cognitive issues on the highest dose, but not all do). Here is an article with Recommendations for Management of Lorlatinib Adverse Events.  

 
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Managing TKI Side Effects

A few key tips seem to hold true across all drugs and treatments. 

  1. It’s almost impossible to drink too much water while you are taking TKIs. Staying hydrated prevents a number of problems. 

  2. Exercise increases circulation and helps with a number of side effects. Choose exercise that takes your physical limitations in consideration. 

  3. If home management of a side effect just doesn't seem to be working, talk to your doctor about alternatives, including a possible TKI dose reduction.

 

Nausea and Vomiting
  • Having a full stomach when you take medication helps a lot, so take the medication after eating food. Some patients find that eating something starchy is best; others find that proteins work better. 

  • Drink plenty of water. 

  • Stay upright for about an hour after taking the medicine. 

  • If nausea persists, a doctor may prescribe anti-nausea medication. 

 

Diarrhea
  • Monitor your diet. Some patients notice certain food intolerances when they track diet and symptoms. Adjust diet accordingly.

  • Keep Imodium or other diarrhea relief medication handy. 

  • Be sure to stay hydrated during bouts of diarrhea to counter the effects of fluid loss. 

  • Some patients describe diarrhea and constipation as a frequent cycle. Getting to know your cycles can help you adjust your lifestyle to accommodate the problem.

 

Constipation 
  • Increase water and fiber consumption.  Foods such as nuts, bran flakes, and raw vegetables can help. 

  • Consider taking stool softeners daily, along with a large glass of water.  

  • Consider taking Miralax (polyethylene glycol) daily, mixed in a large glass of water. 

  • Chew food deliberately and well. 

  • Some patients describe diarrhea and constipation as a frequent cycle. Getting to know your cycles can help you adjust your lifestyle to accommodate the problem.

 

Edema (swelling of arms, hands, feet, and legs)     
  • Reduce salt intake, especially by limiting processed foods. There’s a “silver lining” to doing this--some ROS1ders report that reducing salt intake also lowered their cholesterol levels.

  • Wear compression socks or hose for legs or compression sleeves for arms. 

  • Increase protein intake. 

  • Keep feet elevated as much as possible. 

  • Increase physical activity, and avoid long periods of being sedentary. Walking and gentle stretching can help ease symptoms. Some ROS1ders say water aerobics helped reduce their edema.

  • Some patients have had success with acupuncture.

  • Consider dry brushing a few times a week. 

  • Edema may make blood draws and IVs more difficult. In the days before medical appointments, consider focusing on wearing a compression sleeve. This may make it easier for health care workers to conduct blood draws and administer IVs.

 

Burning Esophagus (sometimes experienced as reflux)
  • If a TKI gets stuck in the esophagus, it can cause an extreme and painful burning sensation. Several patients in the ROS1+ group have reported going to the hospital to treat this pain. To avoid this problem, stay upright (do not lie down) for at least an hour after taking the pills. Take the pill with food, swallow it with a generous amount of water, and perhaps eat a little something after swallowing the pill just to make sure it has gone all the way down. 

 

Fatigue or Tiredness  
  • One thing we have to accept about our lives as cancer patients is that most of us need more sleep. The physical and emotional stresses of disease and treatment just make us more tired. TKIs can make fatigue worse. Try to get more sleep and rest. For those of us with busy and full lives, that is not easy, but it’s necessary. 

  • You may need to ask for help with household chores. If you are still working, maybe there is a way to reduce your hours or reduce your work-related stress. In the USA, patients who have certain types of cancer qualify for Social Security disability via Compassionate Allowances.  

  • If possible, incorporate regular physical activity into your routine. It sounds counter-intuitive, but even a little bit of exercise can help you build energy, strength and endurance, all of which will help you feel less tired in the long run. ROS1ders report benefits from regular exercise as mild as walking or as rigorous as Peloton classes. Exercise within your physical limitations: listen to your body. If you need help figuring out an exercise plan, consider seeking out a personal trainer experienced in working with cancer patients. In the U.S. the Livestrong organization has partnered with the YMCA to offer physical activity programs to cancer survivors.

  • Your medical team or a specialist in management of symptoms and side effects (palliative care specialists in the USA) may be able to help. 

 

Brain Fog or Forgetfulness

Some drugs create a “fog,” or an inability to focus. Some describe difficulty finding words. One patient described the effect this way: “I feel like my brain is always working a little bit underwater. If it were a sound, it would be like underwater boat engines churning sluggishly in a channel off the coast of some forgotten continent.”

  • Get more sleep.

  • Some patients have experienced success with meditation and acupuncture. 

  • Coping skills might include making concrete lists and keeping a good calendar.

  • Doctor-prescribed ADHD (attention deficit hyperactivity disorder) medicines like ritalin have been useful to some.  
     

Slower Heart Rate
  • With some TKIs, a slower heart rate becomes a new normal. Try not to be alarmed that your new beating heart sounds more like that of a marathon runner than an average person.   

  • You may need to describe this relatively common side effect to physicians who are unfamiliar with TKIs. 

  • Scaling back on vigorous activity might increase your heart rate. But remember that some exercise is important to managing side effects. 

  • A lower heart rate can create dizziness. Rise slowly and deliberately. Get your bearings before you get on your feet. 

 

Visual Disturbances
  • Visual disturbances are common especially in the early stages of adjusting to crizotinib. They are more pronounced at night, when going from darkness into light; e.g., moving from a dark bedroom and then flipping on a light switch. Try to avoid the triggers, especially if it affects your safety. Sunglasses might help.

  • Many patients report this side effect lessened considerably after the first month or two on the drug. One patient who continued to struggle with visual disturbances got relief after the doctor lowered the crizotinib dose from 250 to 200 milligrams.  

  • Obtain a referral to an eye specialist if you develop severe vision problems during treatment. 

  • Be careful choosing when you drive (headlights can be bothersome at night). 

  • Some patients choose to relax and enjoy crizotinib's “psychedelic” lights effects.  

 

Difficulty Swallowing
  • Take small bites of food.

  • Remain calm and try to slow down when you swallow.

  • It may be of value to speak to your medical team to see if a swallow assessment is warranted. The difficulty can cause choking.

 

Low Protein Levels
  • You may experience low albumin (protein) in your blood labs. Increase dietary protein intake to counter this issue. Some ROS1ders have found that using protein powder in a smoothie helps to get a lot of grams of protein easily. 

 

Low Iron Levels
  • If your doctor is concerned about your iron level, talk to them about adding an iron supplement.

  • Doctors may prescribe an iron infusion.  

 

Weight Gain

TKIs can affect the metabolism and, in some cases, cause increased appetite while decreasing the sense of feeling “full” or satisfied. Many cancer centers offer nutritional counseling for patients to help manage weight. 

  • Monitor your weight and your diet, and get some help from your healthcare provider.  

  • Many resources focused on diet and cancer recommend having a plant-focused diet; i.e., lots of veggies, protein, and some healthy grains, with limits on red meat, alcohol, processed foods, sugar and carbs. So, consider keeping a large bowl full of raw vegetables in the fridge. (This can help with bowel problems, too.) Opt for home-cooked meals that put you or a caregiver in charge of calories and healthy ingredients. 

  • Physical activity can help with weight and a number of other side effects. ROS1ders describe benefits from walking, exercising in the water, playing pickle ball, golfing, and more. Whatever you enjoy that gets you moving will help you burn calories and manage weight.

  • Don’t beat yourself up if you can’t get yourself to the weight you were at before treatment. Doctors often tell lung cancer patients NOT to try to lose weight quickly. Researchers and practitioners have told some ROS1ders that there is a correlation between being a little heavier than normal and better survival.

  •  It is hard to lose weight while taking a TKI and facing the stress of cancer, so be kind to yourself. Dealing with the problem might simply involve getting bigger clothes.  

 

Taste Changes

It is very common to experience changes in taste. Some describe this as not being able to taste anything. Others experience bitter, tinny, or other changes to taste. The good news is that this side effect usually gets better after a few months on the drug. While going through this, patients find different types of food more or less tolerable. Some need bland food. For others, sweet, savory or spicy foods taste better. Others like extreme tastes. Experiment to determine what tastes okay, and try to be patient. Consult a doctor if this side effect doesn’t go away over time.

 

Dizziness
  • Some patients describe feeling particularly dizzy when rising after lying down, especially on entrectinib. They’ve learned to rise to the upright position carefully and spend a little time getting oriented before standing. 

  • Lie down for a bit if dizzy while standing.  

 

Neuropathy (numbness or tingling, usually in hands and/or feet)
  • For some patients, this side effect can be profound when first beginning the drug and can ease over time. 

  • For neuropathy in toes or feet, try compression socks. For neuropathy in the hands, gloves that offer mild compression may help. Experiment to find the features most helpful to you (level of compression, knee-high versus thigh-high, etc.).

  • Some report that massage or acupuncture help.

  • Ask your care team if  taking vitamin B-12 might help.

 

Skin Problems

Some patients experience dry skin or rashes as side effects of TKIs. Good moisturizing creams and aloe lotions can usually help with dry skin, and topical antihistamine lotions like calamine/caladryl, or hydrocortisone creams can help with itching. Sometimes a stronger typical steroid is necessary and can be prescribed by a doctor. 

  • Always wear sunblock. TKIs can make you more sensitive to sunlight, so sun can exacerbate skin problems. 

  • Try an oatmeal bath or cold shower. 

  • Try an ice pack on affected areas.

  • Some patients have had some luck with acupuncture.

  • Some patients report an ache on the surface of the skin and extra sensitivity upon touch resulting in pain. Most say this wanes over time. 

  • Tips on managing skin rashes from Lungcancer.net.  

 
Problems with muscles, connective tissue and bones

Entrectinib, in particular, seems to create struggles with muscles and bones. One ROS1der has found that stretching every morning and easing slowly into activities is a small change that helped her avoid further injuries. Still, problems should be reported to your doctor for care. 

Side Effects Requiring Medical Management

Don't try to manage these serious side effects alone

High Cholesterol (common with lorlatinib)

Patients on lorlatinib should have their cholesterol monitored regularly.  Sometimes, dietary changes can help lower cholesterol, but often patients need to take a statin or other medication to bring levels into a normal range. 

 

Liver Problems (can happen on crizotinib, entrectinib, or lorlatinib)

This side effect would be noted in blood work during a regular oncology appointment. If your liver enzymes are elevated, your doctor may ask you to stop taking your TKI for a few days or weeks and then resume at a reduced dose. Some patients need to find alternative treatments. It may be best to reduce or eliminate alcohol consumption to reduce strain on the liver. In some cases, a different TKI might be better tolerated. 

 

Low Testosterone, or Low T, in Men (primarily crizotinib)

Low testosterone in men can affect mood, energy, sleep, and erectile dysfunction. If you are experiencing any of these systems, ask your care team if a prescription for a testosterone replacement medication like Androgel would help. 

 

Elevated Creatinine 

This reflects a strain on the kidneys, but might just be due to dehydration. Your oncologist can tell you whether your creatinine level is a concern and whether a consultation with a nephrologist (kidney specialist) would be helpful.

 

Medically reviewed by ROS1 Clinician-Researchers
Last updated 19-Feb-2022