Randomized clinical trial testing the efficacy and safety of 0.5% colchicine cream versus photodynamic therapy with methyl aminolevulinate in the treatment of skin field cancerization: study protocol

Abstract

BackgroundThe primary clinical manifestation of skin field cancerization is the presence of actinic keratoses (AKs). Current treatments for AKs related to skin field cancerization include photodynamic therapy (PDT) and colchicine. The objective of this study is to evaluate the efficacy and safety of 0.5% colchicine cream versus PDT with methyl aminolevulinate (MAL-PDT) in the treatment of skin field cancerization.MethodsIn a randomized controlled and open clinical trial with a blind histopathological and immunohistochemical analysis, 36 patients with up to 10 AKs on their forearms will be included from the outpatient clinic. The forearms will be randomized into two groups, clinically evaluated and biopsied for histopathology and immunohistochemistry (p53 and Ki67). One forearm will be treated with 0.5% colchicine cream for 10 days, and the other forearm will receive one session of MAL-PDT; the forearms will subsequently be reassessed clinically and histologically after 60 days (T60) of treatment. The primary endpoint will be the point of complete clearance of AKs in T60. The sample size will enable a detection in the reduction of over 10% in AK counts between the groups with power of 0.9 and an alpha of 0.05, accounting for an estimated dropout rate of 10%, resulting in 36 patients (72 forearms). All participants included in the randomized study will be part of the analysis, and the final outcomes of any dropouts will be the value of their last visit (LOCF). The statistical analysis will be performed using SPSS 22.0, and a p value < 5% will be considered to be significant.DiscussionIt is expected that colchicine will be superior to MAL-PDT in reducing AKs and in the skin field cancerization, and there will be good tolerability in both groups. Colchicine intervention is novel in that it provides a new alternative to MAL-PDT. Moreover, this drug is inexpensive that may be a potential treatment of skin field cancerization that can be prescribed in public health systems with good results.Trial registrationThe trial is registered in Brazilian Registry for Clinical Trials (Registration number: RBR-8y3sj9, date assigned May 4, 2016, retrospectively registered).

A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies

“…35 Of note, this review is limited to face and scalp, and significantly poorer outcomes are routinely reported for upper limbs. 36 The natural history of actinic keratosis demonstrates a very high turnover, with large numbers developing, regressing and recurring over time. 1 This labile nature emphasises the need for future studies to more accurately 74.5% 25 Primary study results (direct data) are in bold; review study estimates are in italics; and calculated percentages are underlined.…”

“…Treatment combinations appear to improve efficacy compared to monotherapies but at significant additional cost 35 . Of note, this review is limited to face and scalp, and significantly poorer outcomes are routinely reported for upper limbs 36 …”

Nanomedicine in Clinical Photodynamic Therapy for the Treatment of Brain Tumors

“…The therapeutic application of PDT for cancer began in the late 1970s with tests of the effects of light irradiation on hematoporphyrin derivatives (HPDs) in five patients with bladder cancer [ 48 ]. Since this initial work, more than 250 clinical trials of PDT have been conducted, with targets ranging from pre-malignant skin cancers [ 49 , 50 , 51 , 52 , 53 , 54 ] to peritoneal carcinomatosis [ 55 , 56 ], gastrointestinal cancers [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ], lung cancers [ 65 ], and brain tumors [ 66 , 67 ]. Although many clinical trials of PDT for the treatment of malignant brain tumors have been conducted, most of them are phase I or II trials [ 66 ].…”