Discussion
In our experience, administration of systemic bevacizumab for RRP in
children results in rapid improvement in voice quality, symptom relief
and reduced need for surgical debridement. The treatment was well
tolerated and side effects were minimal and included mild proteinuria
and brief epistaxis. This is not surprising as the dose and frequency we
use is lower than that used for treating children with cancer such as
brain tumors. Although bevacizumab controls the growth of papillomas, it
is unlikely that it will be curative. This raises concerns about long
term use of bevacizumab in young children. The possible long-term
effects of bevacizumab has to be balanced against the risks of repeated
surgical procedures, anesthesia and lower voice quality. Our approach is
to use the minimum dose and frequency necessary to avoid surgical
debridements. To this end, we rapidly increase the interval between
doses until papillomas recur or symptoms return.
The use of adjuvant therapies in the management of RRP has had mixed
results1–5. A 2003 case series on the use of
intralesional cidofovir on four children with RRP had heterogenous
results with one of the patients achieving complete remission for 15
months5. A 2013 case series that evaluated the effects
of three injections of intralesional bevacizumab in 10 children with RRP
saw a median surgical procedure time increase of 5.9 weeks1. All three of our patients did not achieve
significant benefit from use of intralesional cidofovir or bevacizumab.
Our case series is limited by a short follow up of patients which
lessens our ability to determine long term efficacy as well as late side
effects. Our patients lacked standardized surveys to assess symptom
severity before and after starting treatment. HPV typing was not
assessed which limited our ability to draw conclusions about the
relationship between treatment response and HPV type.
Conflict of interest: Julina Ongkasuwan receives royalties from Springer
and Elsevier. There are no other conflicts of interests to report.
Acknowledgements: There are no acknowledgements.
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Figure Legends:
FIGURE 1 Laryngoscopy Before and After Bevacizumab in Patient 1. A-C
show images from the last laryngoscopy performed before Bevacizumab.
Figure A shows papilloma in epiglottis, figure B in glottis and figure C
in trachea. Figures D to F show the first post bevacizumab laryngoscopy
with minor papilloma laryngeal side of epiglottis (D), vocal folds (E)
and a clear trachea. Figures G-I shows the most recent laryngoscopy
showing minor papilloma in vocal folds (G) with persistently papilloma
free trachea (H and I).
FIGURE 2 Laryngoscopy Before and After Bevacizumab in Patient 2. Figure
A shows last laryngoscopy performed before procedure which shows bulky
papilloma along entire length of vocal folds. Figures B-D show first
laryngoscopy after bevacizumab which shows minimal papillomas on vocal
folds. Figure E shows laryngoscopy performed after 4 cycles which does
not show any papillomas. Picture F shows flexible nasolaryngoscopy
obtained after 8 cycles of bevacizumab which also shows no papillomas.