Study

Design

Cohort

Outcomes

Bevacizumab

Mohr et al. (2014)

Case series

Intravenous: 5–15 mg/kg per dose q 2–3 weeks initially, then increase interval

N = 5

4 adults

1 child, 8 years of age

Immediate response

Very good partial remission or partial response in all patients

Sidell et al. (2014)

Case series

Intralesional injection:

5–45 mg dose × 5 doses

q 4–6 weeks with 532 nm KTP laser ablation

N = 9

Median age 8 years

Range 3–21 years

Median 58% improvement in Derkay score

↑ Median surgical interval time 2.05X

Rogers et al. (2013)

Case series

Intralesional injection:

2.5 mg/mL × 3 doses

q 2–3 weeks with 532 nm

KTP laser ablation

N = 10

Range 18 months–18 years

Statistically significant:

↑ Median surgical interval by 5.9 weeks

↓ Median number of procedures by 4 per year

↓ Derkay score by 6

↑ Median total PVRQOL score by 25.5

↑ Median emotional PVRQOL score by 11.3

↑ Median physical PVRQOL score by 14.3

Zeitels et al. 2011

Prospective open-label trial

Intralesional injection:

7.5–12.5 mg in × 4 doses q 6 weeks into vocal fold with worse disease

Opposite vocal fold sham injection with saline

± 532 nm KTP laser as needed

N = 20 adults with bilateral vocal fold disease

3/20—No disease in either vocal fold

16/17—Less disease in treated vocal fold

1/17—More disease in treated vocal fold

20/20 Improved:

Vocal function, acoustic and aerodynamic measures of voice, VRQOL scores

Interferon

Suter-Montano et al. (2013)

Case series

Peg-IFNα-2a at 180 mcg weekly × 6 months

In 3rd month, +GM-CSF 400 mcg weekly × 2 months

N = 11 adults

3 patients had tracheostomy removed

Mean improvement in VRQOL measures

↓ Number of surgical interventions required

Nodarse-Cuni et al. (2004)

Case series

IM injection IFNα-2b

Induction:

10⁵ IU/Kg in children

6 × 10⁶ IU in adults

Maintenance (up to 2 years):

5 × 10⁴ IU/Kg in children

3 × 10⁶ IU in adults

N = 169

84 adults

85 children

Relapse frequency:

↓ 74% in children

↓ 79% in adults

Complete resolution in 1^st presentation patients:

45% of children

88% of adults

At study completion:

58% of children in remission

82% of adults in remission

Interferon and BCG

Avramov et al. (2014)

3 Parallel case series

Series 1:

CO₂ laser ablation + 6–12 transdermal applications of BCG

Series 2:

CO₂ laser ablation +

α-Interferon 3 million IU 5 times per week for 1 month, then 3 million IU 3 times per week for 1 month, then 3 million IU once per week

Series 3:

Surgery alone

(No mention of how patients were allocated)

N = 16 adults

N = 11 adults

N = 16 adults

2/16 had a relapse (follow-up 36 months)

3/11 had a relapse (follow-up 45 months)

6/16 had a relapse (follow-up 48 months)

Interferon and Cidofovir

Armbruster et al. (2001)

Case report

Interferon α-2b

5 × 106 Units 3 times per week x 6 months combined with

Cidofovir 5 mg/Kg per week × 2 weeks then

5 mg/Kg q 2 weeks for total 6 months

N = 1 adult

Regression of laryngeal and intrapulmonary disease

Indole 3 Carbinol

Rosen and Bryson (2004)

Prospective open-label trial

I3C 200 mg orally twice daily

N = 33

24 adults

9 children

Mean follow-up 4.8 years

All patients:

33% remission

30% ↓ need for surgery

36% no response

Children:

1/9—complete response

3/9—partial response

5/9—no response

Acyclovir

Chaturvedi et al. (2014)

Case series

Post-surgical oral acyclovir 800 mg 5 times per day × 5 days

N = 3 adults

2/3—remission at end of 1 year follow-up

Vaccination and Immune Therapy

Meacham and Thompson (2017)

4 Parallel case series

Series 1:

Debridement and cidofovir

Series 2:

Debridement and MMR

Series 3:

Exposure to cidofovir and MMR

Series 4:

Debridement only

N = 15 children

Range 1–16 years

N = 5

N = 6

N = 3

N = 1

No significant difference in number and frequency of required treatments or rates of remission across series

Beaumanis and Elmaraghy (2016)

Case report

Quadrivalent HPV vaccine

N = 1 child

4 year old

Improved clinical course

Hermann et al. (2016)

Uncontrolled intervention study

3 Doses of quadrivalent HPV vaccine

N = 9 children

Range 9–17 years

No significant difference in clinical course, anatomical score, inter-surgical interval or number of surgeries needed at 1-year follow-up

Young et al. (2015)

Case series

Quadrivalent HPV vaccine

N = 20

Significant increase in inter-surgical interval

8/20—Complete remission

5/20—Partial remission

Chirila and Bolboaca (2014)

Case series

Quadrivalent HPV vaccine

N = 13

Patients with recurrences after failed treatment with cidofovir

85% had no recurrence at 1-year follow-up

Lei et al. (2012)

Randomized prospective trial

Arm 1:

Topical MMR vaccine at site of excised lesions

Arm 2:

Excision only

N = 26 children

Longer period of remission in MMR but difference was not significant

Derkay et al. (2005)

Open-label, single arm intervention study

Surgery followed by HspE7 500 mcg subcutaneously monthly × 3 doses

N = 27 children

Range 2–18 years