Non-melanoma skin cancers (NMSC) are the most commonly occurring cancers worldwide and the
incidence of these malignancies is steadily rising secondary to the advancing age of the
general population as well as sun exposure. Gold standard treatment modalities for NMSC
include surgical excision and radiation therapy. Both of these treatments are accompanied by
risks to the patient including pain, bleeding, infection, scarring and pigment alterations.
Larger lesions necessitate treatment of larger areas of skin, which can worsen treatment
related toxicities. Patients with NMSC of the head and neck may be particularly concerned
regarding these risks as this region is cosmetically sensitive.
For surgery, a recommended margin of 0.5-1.0cm of normal tissue is removed beyond the lesion
boarder to decrease risk of recurrence. In an area like the face, reconstruction of excision
defects and ultimately aesthetic outcomes are of utmost importance. Particularly large skin
can sometimes necessitate rotational flaps or even skin grafting, both of which have
drawbacks in terms of healing, scarring, and surgical complications. A similar issue of
margins arises with radiation. For patients undergoing radiation treatment with an
orthovoltage a margin of 1.0cm is added beyond the clinical boarders of the lesion, while for
patients being treated on an electron unit, a 1.5cm margin is added.
Currently, there are no routinely used neoadjuvant treatment option that can be used to help
decrease lesion size and therefore limit toxicities associated with definitive treatment
(surgery or radiation). However, these has be recent work looking at neoadjuvant use of
concentrated hydrogen peroxide in reduction of lesion size (5).
Hydrogen peroxide a product of respiration in mitochondria and an important oxidizing agent
in biological system. As it is a potent oxidizing agent, hydrogen peroxide can exert a role
in oxidative stress, although the exact mechanism through which this occurs is not yet known.
Giulivi and Davies (1) propose that hydrogen peroxide may interact with hemoglobin in the
dermal capillaries producing oxidized forms of hemoglobin such as ferryl hemoglobin which is
highly reactive. It is therefore possible that hydrogen peroxide could cause necrogenous
oxidation and oxygen induced apoptosis of cells in NMSC.
Dilute hydrogen peroxide it is used frequently as a topical antiseptic and hemostatic agent
(2). These effects are generally achieved with topical application of 3% hydrogen peroxide to
the skin, with little to no side effects for patients aside from some mild discomfort. As far
as potential clinical application of more concentrated hydrogen peroxide, a previous
investigation examining the use of hydrogen peroxide at or above a concentration of 23% in
the treatment of seborrheic keratosis found that the mean number of benign lesions remaining
90 days after treatment was significantly lower in the hydrogen peroxide group compared to
placebo (3). The average number of applications of hydrogen peroxide was 6, separated by
approximately one-week intervals (3). In this study, the only side effect from application of
the hydrogen peroxide solution was less than ten minutes of "burning" at the application site
(3). Hydrogen peroxide has also been used in combination with other topical treatments such
as non-steroidal anti-inflammatories (NSAIDs) to successfully combat precancerous lesions
such as actinic keratosis (4) as well as part of photodynamic therapy protocols in the
treatment of skin cancers.
Recently Mundi et al. (5) published a case series looking at the role of a topical
application of 33% hydrogen peroxide as neoadjuvant therapy before surgical excision. This
series included 11 patients and a total of 17 lesions. Patients received multiple topical
applications of hydrogen peroxide and were evaluated 4 weeks after the initial treatment to
assess response. There was complete pathological response in 53% of patients and the remained
had a statistically significant reduction in the size of the lesion requiring a smaller
surgical excision. Although promising, this was a small, non-randomized, non-controlled proof
of concept study. Further work is required before this type of treatment could be adopted
commonly or used of trial.
However, given its relatively benign nature and previous efficacy in treating other skin
growths, hydrogen peroxide may represent a simple yet effective method at shrinking NMSC of
the head and neck before they are excised or radiated. In doing so, it could minimize the
invasiveness of surgical excision thereby accelerating healing and improving aesthetic
outcomes for patients. If patients are being treated with radiation, we may be able to use
smaller radiation fields with less side effects, better cosmesis and improved local control.
This double-blind placebo randomized controlled trial will seek to investigate the role of
neoadjuvant hydrogen peroxide prior to definitive treatment with either surgery or radiation.
For the purposes of this trial a concentration of 30% hydrogen peroxide will be used as this
is the highest concentration easily available.