Trial Information

A Clinical Trial of ALA Photodynamic Therapy for Treatment of Actinic Cheilitis in Patients With Squamous Cell Carcinoma of the Lip.

BACKGROUND:

SCC of the lip is commonly surrounded by extensive AC, which may affect part or all of the
lip vermillion. While Mohs surgical technique with complete margin control is the preferred
treatment for SCC at critical locations such as the lip, this technique is complicated by
surrounding AC. AC and SCC in situ at the tumor edge make it difficult to achieve margins
clear of dysplasia and as a result extra tissue beyond the invasive SCC often needs to be
excised to ensure that the entire tumor is removed.

Non-surgical treatments when used alone to treat SCC give lower cure rates than surgical
removal, and thus are not recommended as they place the subject at risk for recurrence and
metastatic disease. Although one study reported high SCC clearance rates with PDT alone
(24/25 SCCs histologically cleared), recurrence of 2 SCCs occurred and a metastasis to a LN
was seen in one patient. (Kubler et al.)

Given that PDT has been shown to have significant efficacy for actinic keratoses and actinic
cheilitis but is inadequate as primary treatment of lip SCC, we propose that PDT may be a
useful adjunct to surgical resection, allowing for less extensive surgery after the
dysplasia is addressed with PDT and potentially a lower recurrence rate. Although imiquimod
and 5-FU are also used to treat cutaneous dysplasia, many favor PDT treatment due to its
greater tolerability, shorter healing time, and more predictable host response.

There is significant data on the efficacy of PDT for treatment of actinic keratoses (AKs)
and PDT is now FDA approved for treatment of AKs. (Piacquadio et al). Data on PDT for
treatment of AC is much more limited, but small studies and case reports do indicate
successful treatment of AC with regimens utilizing either topical 5-aminolevulinic acid
(5-ALA), or a similar compound, methylaminopentanoate (MAL). The largest study with 5-ALA
reports complete clinical clearance in 13/19 patients treated with 1 to 3 treatments of ALA
plus Pulsed-dye laser (Alexiades). Sotiriou et al report that with two PDT treatments 8/10
patients had complete clinical and histologic clearance (Sotiriou). Case reports indicate
similar success (Kodama; Stender). Efficacy has also been shown with MAL PDT. One study
found that with two sessions of MAL + red light PDT complete histologic/ clinical clearance
was seen in 7/15 cases of AC and partial clearance was seen in an additional 7/15 (Berking
et al). Smaller studies and case reports have shown even higher response rates without
clinical recurrence during short-term follow-up (Rossi et al; Hauschild et al). We have
chosen 5-ALA plus blue light for PDT treatment in this study because it is FDA approved for
treatment of AKs and ALA is available in the United States.

Specific Aims:

1. To determine whether pre-operative treatment of the lips with ALA PDT can reduce the
size of post-surgical defects (scars) in subjects with AC and lip SCC

2. To determine whether ALA PDT applied to the lips can effectively clear actinic
cheilitis (AC) and SCC in-situ (SCC-is) of the lip.

3. To assess the tolerability of ALA PDT for treatment of AC and SCC-is of the lips