Martin’s Help Sheet: CHANGING TKI DOSAGE STRENGTH AND/OR CYCLE FREQUENCY

Many patients with secondary kidney cancer are put on drugs called tyrosine kinase inhibitors (TKIs), the main ones being sunitinib (Sutent), pazopanib (Votrient), or axitinib (Inlyta). Whilst these drugs are generally very effective, most patients suffer some side effects. Most drugs will have a dedicated website describing these, for example, Possible Sutent Side Effects.

For some, the side effects can have a severe effect on quality of life. It is, therefore, important to keep a balance between the clinical effectiveness of the drug, and the patient’s quality of life. If the patient is having trouble tolerating the drug, often changes can be made that allow the patient to keep taking the drug and have a decent quality of life:

Dosage strength (formally called dose titration)

These drugs come in a variety of strengths, and if you find the dose prescribed causes you severe side effects, speak your oncologist about reducing the dose. Often patients are started on the highest dose, but find they can’t tolerate it.

One oncologist commented to a patient “each body processes what it needs then the rest of it wanders around looking for trouble”. For this reason, a lower dosage does not necessary mean reduced effectiveness. Some patients have had good results on a lower dose.

Patients respond to drugs differently because each patient is different, and each has a maximum dosage they can tolerate. For those taking pazopanib and axitinib, dose reduction may be the only option available for limiting side effects and continuing on the treatment, as these drugs are taken continuously.

For more information, please see the Votrient Dosage Guide.

Patients have said:

“Saw my oncologist on Wednesday and he has reduced my dose of XXXXX to 600mg due to very high BP and extreme fatigue. Second day of reduced dose and think I feel a little less fatigued……. Actually been shopping this morning”

“Definitely try reduced dose. I ended up in hospital after 2 weeks on full whack of XXXXX. Lower dose worked really well and although it was still hard going I managed to get through 11 cycles with an almost complete response!”

Although not a means of managing side effects, there has been a recent study that found that increasing doses above the normal recommended if the TKI has shown progression can extend overall survival and could be considered as a further treatment option. However, this will likely result in increased side effects, which at normal dose can be harsh for some, so should perhaps only be considered when other treatments have failed.

Sunitinib – Change of cycle profile

The recommended regime for taking sunitinib is to take one tablet a day for 4 weeks, then have a two week break, giving a 6-week cycle. Most patients are given a starting dosage of 50mg, which is the highest strength.

However, many patients have changed to a 2-week on/1 week off/2-week on/1 week off profile, still comprising a 6-week cycle. The total dosage over the 6 weeks is unchanged. A recent clinical trial found that the efficacy of the drug is as good on this regime, but patients found it to be a more suitable regime to cope with, because of lower toxicity.

Patient comments suggest this may be down to:

• Not getting any side effects in the first week. With the traditional 4/2 regime this still means a 3-week block of side effects, which in some instances, such a sore mouth, can continue to get worse over that period. On a 2/1 regime, the patient only has to endure the side effects for one week before effectively getting a 2-week break. Both physically and psychologically, patients have found this regime kinder.

• There is also anecdotal evidence from patients that when they have taken a longer break of say 3 or 4 weeks, they found the side effects more severe than they had been prior to the break upon resumption. It may therefore be that constantly taking a 2-week break will result in routinely experiencing more severe side effects than taking a 1-week break.

Please help other patients:

Please keep us updated with useful information that will help other cancer patients. You can email us with your tips so we can regularly add to this resource.

Thanks to all the KCSN members for their input, and especially to Martin for his patience and willingness to collate this information to help and support others.

Written April 2016. Reviewed October 2016

Download a pdf of this help sheet here: A guide to changing TKI dose and cycle frequency