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Sunitinib (Sutent) Side Effects and Management


What side effects were shown in clinical trials of sunitinib (Sutent) for GIST?
Can  sunitinib (Sutent) affect thyroid function?
What tips help to cope with skin side effects of sunitinib?
Can sunitinib (Sutent) affect heart function?
What treatment can control hypertension related to sunitinib?

What side effects were shown in clinical trials of sunitinib (Sutent) for GIST?

The table below lists the percentages of patients who showed various side effects in the available clinical trial data for sunitinib (Sutent).  Note that a single patient will not experience all or even many of these events.  Grade 1-2 side effects are less severe than grade 3-4 side effects.

GIST patients' tips for dealing with sunitiniib side effects are collected in our GIST Support Wiki.

Click the following link to a practical free-access paper about dealing with side effects:
Wood, L.S.  Managing Side Effects of Sorafenib and Sunitinib.  Community Oncology 2006: 3(9):558-562.


Percentage of patients showing different Sunitinib (Sutent) side effects in different clinical trials. (Note that in the Phase I-II and Worldwide treatment-use trials, only non-hematological side effects affecting at least 20% of subjects were reported.)  NR= not reported.

Side EffectPhase I-II trial
(N=97)
Phase III trial
(N=202)
Worldwide treatment-Use trial (N=1117)
Non-hematological
effects
Grade
1-2
Grade
3-4
Grade
1-2
Grade
3-4
Grade
1-2
Grade
3-4
fatigue56%10%29%5%33%8.3%
diarrhea49%7%26%3%34%5%
skin discoloration40%0%25%0%NRNR
nausea36%4%23%1%26%2%
anorexia (appetite loss)NRNR19%0%21%2.1%
dysgeusia (taste changes)NRNR18%0%NRNR
stomatitis (sore mouth)28%3%15%1%20%2.1%
vomitingNRNR15%1%19%2.2%
hand-foot syndrome33%7%9%4%NRNR
rashNRNR12%1%NRNR
astheniaNRNR9%3%NRNR
mucosal inflammationNRNR12%0%21%2.1%
dyspepsiaNRNR11%1%NRNR
hypertension12%17%8%3%17%5.2%
epistaxis (nosebleed)NRNR7%0%NRNR
hair-color changeNRNR7%0%NRNR
dry mouthNRNR6%0%NRNR
glossodynia (sore tongue)NRNR6%0%NRNR
Hematological effects
anemiaNRNR58%4%10%4%
leukopeniaNRNR52%4%NRNR
neutropeniaNRNR43%10%11%8%
lymphopeniaNRNR40%10%NRNR
thrombocytopeniaNRNR35%5%14%5%

Sutent is not as well tolerated as imatinib, but the side effects are manageable for many people without dose reductions.  Dose reductions can be helpful for patients with severe side effects.  In the worldwide treatment-use trial of sunitinib, over half of patients had temporary dose interruptions, and over 40% had dose reductions.

Note that the side effects shown in the table above were reported for the 50-mg dose for 4 weeks followed by a 2-week washout period.  A continuous dosing schedule (lower dose, no washout period) may reduce side effects according to an ASCO presentation by George et al, 2008


Can sunitinib (Sutent) affect thyroid function?

Hypothyroidism, a decrease in thyroid hormone production,  is an additional side effect of sunitinib that has been recognized only recently.  According to data for patients in the Phase I/II trial of sunitinib (Sutent), 36% developed hypothyroidism during treatment with sunitinib, and the incidence of hypothyroidism increased with duration of treatment.  These findings were published in November 2006 by Desai et al in the Annals of Internal Medicine (click for abstract).  A free-access patient information summary is available at the journal site to read online or to print as a pdf.  Desai et al report that "15 of 42 patients (36%) developed hypothyroidism after an average of 50 weeks of therapy (range 12 to 94 weeks)" and an additional 7 patients (17%) had an abnormal serum thyroid stimulating hormone (TSH) test result at at least one point during treatment.  Two patients' thyroid glands atrophied, becoming undetectable on imaging.  All patients responded to treatment with L-thyroxine.  Desai et al stated that "hypothyroidism is easily treated and is not in itself an indication for the discontinuation of sunitinib therapy given its effectiveness in treating life-threatening conditions." 

Additional reports of hypothyroidism in patients treated with sunitinib have found varying incidences, but the unbiased prospective studies estimate that 36-46% of patients are affected (Mannavola et al, 2007; Rini et al, 2007; Wong et al, 2007; Wolter, Dumez and  Schöffski, 2007Wolter et al, 2008; Garfield et al, 2008; Vetter et al, 2008).  For a discussion of hypotheses about exactly how the thyroid is damaged by sunitinib and other tyrosine kinase inhibitors, see Illouz et al (2009).

Recommendations include:

  • baseline thyroid testing before starting sunitinib therapy
  • routine monitoring at least every 3 months to detect changes in thyroid function
  • consultation with an endocriinologist
  • prompt treatment with L-thyroxine (prescription thyroid hormone replacement) if hypothyroidism is detected

Experts Dr. Patrick Schöffski and Dr. Pascal Wolter, who reported on the only prospective study of thyroid function in patients before and after starting sunitinib therapy (Wolter et al, 2008), have kindly answered questions on this topic in a contribution to our Ask the Professional section.  Please link to Thyroid Damage from Tyrosine Kinase Inhibitors

What tips help to cope with skin side effects of sunitinib?

Hand-foot syndrome involves thickened skin on the soles of the feet and palms of the hands, plus tenderness and sometimes sores.  This is a troubling side effect for those patients who are affected.  Sunitinib also may interfere with healing of skin cuts or sores.

Dr. Mario Lacouture has answered some questions about these and other skin-related problems in this piece in our Ask the Professional page: 
Skin-Related Side Effects of Imatinib & Sunitinib.

For a free-access article on this topic, link to the following:
Evolving Strategies for the Management of Hand-Foot Skin Reaction Associated with the Multitargeted Kinase Inhibitors Sorafenib and Sunitinib, by Mario E. Lacouture et al, in The Oncologist, September 2008.

Other tips collected from GIST patients who belong to our listserv are available on our GIST Support Wiki.

Can sunitinib (Sutent) affect heart function?

Heart function changes have occurred in some patients taking sunitinib (Sutent).  Chu et al (2007) reviewed data for the GIST patients in the Phase I-II sunitinib trials to look for cardiotoxicity, and they documented cardiovascular events in 11% of patients.  They recommended that all patients on sunitinib be monitored for hypertension and decreases in the heart's left ventricle ejection fraction (a measure of pumping capacity).  Cardiotoxicity of several types was reported for about 2% of patients in the worldwide Treatment-use trial of sunitinib for GIST, as shown in Table 5 of the Seddon et al (2008) poster.  However, data from this trial may be less consistently recorded since patients were seen at numerous different facilities all around the world.    Additional data about cardiotoxicity from sunitinib comes from patients treated with the drug for renal cell carcinoma (kidney cancer).  For a PubMed search on sunitinib and cardiotoxity click here.

Your oncologist will monitor you for this potential side effect.

What treatment can control hypertension related to sunitinib?


For a discussion of drug treatments for hypertension associated with sunitinib, see the following Q&A piece on our Ask the Professional page:
Sunitinib and Hypertension by Robert Maki, MD PhD and Michele Bradshaw, PharmD



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