calcipotriene and Keratosis--Actinic

Actinic Keratosis (AK) is a premalignant lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Topical 5-Fluorouracil (5-FU) and imiquimod have been used for field-directed therapy for AK; however, their use is limited by intolerable skin reactions and long treatment durations.. To assess current data on the efficacy, tolerability, and long-term effectiveness of topical calcipotriol plus 5-FU combination for the field-directed therapy of AK. The systematic review will include a critical evaluation of the available evidence.. A systematic review of the literature was performed in August 2021 using the EMBASE and MEDLINE databases. Studies that assess the use of calcipotriol and 5-FU to treat actinic keratosis (AK) and cSCC prevention were included.. In total, four studies met the inclusion criteria. Our final analysis included three articles. One clinical trial evaluated the efficacy of calcipotriol plus 5-FU in treating AK. Another clinical trial evaluated the long-term effect of calcipotriol plus 5-FU in prevention of cSCC. A retrospective study evaluated the use of calcipotriol plus 5-FU with cryotherapy.. A limitation of this systematic review is the limited number of clinical trials that examine the combination of 5-FU plus calcipotriol in treating AK. The active control arm (Petroleum jelly plus 5-FU combination) is not equivalent to topical 5-FU monotherapy; hence, no superiority claim can be made vs topical 5-FU in terms of efficacy.. Calcipotriol plus 5-FU reduced greater number of AKs in the treated area (25 cm2) when compared to 5-FU plus petroleum jelly, but only 27% of participants had complete clearance on the face at week-8. Calcipotriol plus 5-FU lowered the risk of cSCC on the face and scalp area over a 3-year period. Adequate and well-controlled studies are needed to compare the efficacy of calcipotriol plus 5-FU to 5-FU monotherapy, and other FDA-approved topical drugs such as imiquimod cream and tirbanibulin ointment. J Drugs Dermatol. 2022;21(1):60-65. doi:10.36849/JDD.6632.

Topics: Acetamides; Calcitriol; Carcinoma, Squamous Cell; Fluorouracil; Humans; Keratosis, Actinic; Morpholines; Pyridines; Retrospective Studies; Skin Neoplasms; Treatment Outcome

The goal of field cancerization treatment is to reduce the risk of developing keratinocyte carcinoma. Selecting the appropriate therapy depends on the degree of field cancerization and the number of invasive cutaneous squamous cell carcinomas. Other considerations include treatment efficacy, cost, side effects, and patient preference. Field therapies are preferred because they address clinically visible disease and subclinical atypia. However, lesion-directed therapies are useful for lesions that are more difficult to treat or those where a histologic diagnosis is required. Patients with extensive field cancerization benefit from a combination of field-directed and lesion-directed treatments. The second article in this continuing medical education series provides a framework to guide evidence-based decision making for field cancerization treatment.

Topics: Administration, Cutaneous; Antineoplastic Combined Chemotherapy Protocols; Calcitriol; Carcinogenesis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Clinical Decision-Making; Combined Modality Therapy; Cryosurgery; Dermatology; Drug Synergism; Evidence-Based Medicine; Fluorouracil; Humans; Injections, Intralesional; Keratosis, Actinic; Medical Oncology; Mohs Surgery; Neoplasms, Second Primary; Photochemotherapy; Randomized Controlled Trials as Topic; Skin; Skin Neoplasms; Skin Pigmentation; Treatment Outcome; Ultraviolet Rays

To enhance the efficacy of photodynamic therapy (PDT) for actinic keratosis (AKs), physical and chemical pre-treatments, such as calcipotriol (CAL) have been suggested. To compare the long-term 12-month efficacy and safety between methylaminolevulinate (MAL)-PDT and prior application of topical CAL versus conventional MAL-PDT for AKs of the scalp. Twenty patients with multiple AKs on the scalp were randomized to receive conventional PDT on one side of the scalp and CAL-assisted PDT, in which CAL was applied daily for 15 days beforehand, on the other side. Patients were evaluated for AK clearance at three, six and 12 months thereafter. All 20 patients completed the study. At three months, overall AK clearance was 92.07% and 82.04% for CAL-PDT and conventional PDT, respectively (p < 0.001). Similar results were found at six and 12 months: 92.07% and 81.69% (p < 0.001), and 90.69% and 77.46% (p < 0.001) for CAL-PDT and conventional PDT, respectively. Grade I AKs showed a similar response rate for both sides (p = 0.055) at three months and significant differences were obtained at six (p = 0.001) and 12 months (p < 0.001) for CAL-PDT and conventional PDT. Grade II AKs showed greater improvement on the CAL-PDT side (89.55% vs 62.90%) (p < 0.001) at three months. No difference was found at six and 12 months. CAL-PDT proved to be safe and more effective than conventional PDT for the treatment of AKs on the scalp after 12 months. CAL pre-treatment may have enhanced the efficacy of PDT for AK treatment, however, larger trials are needed to corroborate our findings.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Calcitriol; Dermatologic Agents; Follow-Up Studies; Humans; Keratosis, Actinic; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Prospective Studies; Scalp Dermatoses

Topics: Ablation Techniques; Administration, Topical; Calcitriol; Combined Modality Therapy; Humans; Keratosis, Actinic; Laser Therapy; Photochemotherapy; Preoperative Care; Prospective Studies; Treatment Outcome

This split-face design study evaluated the effect of pretreatment with calcipotriol prior to daylight-mediated photodynamic therapy (DL-PDT) in patients with actinic keratosis (AK). The study included 11 subjects with grade I-III AK (mean age: 55 years). Subjects used once-daily calcipotriol 50 mcg/g ointment on half the face/scalp for 15 days prior to DL-PDT. Evaluations of efficacy, safety and subject satisfaction were conducted 48 h and 7 days after treatment, and at 1- and 3-month follow-ups. Three months after treatment with calcipotriol/DL-PDT and DL-PDT alone, the complete response rate was 85% and 70%, respectively. The partial response rate was 12% and 25%, respectively. During calcipotriol pretreatment, 6 subjects reported erythema and moderate desquamation. In 7 subjects, calcipotriol/DL-PDT was associated with more marked erythema than that observed with DL-PDT alone. Eight subjects reported they preferred DL-PDT alone due to the inconvenience caused by the daily application of calcipotriol and the related erythema and desquamation. Although calcipotriol improved the efficacy of DL-PDT, it may not be applicable to all patients. DL-PDT is a simpler, safer and more convenient option than conventional-PDT. Therefore, the use of additional agents prolonging the course of treatment and increasing cost may diminish the advantages currently offered by DL-PDT.

Topics: Adult; Aged; Aminolevulinic Acid; Calcitriol; Dermatologic Agents; Face; Female; Humans; Keratosis, Actinic; Male; Middle Aged; Patient Satisfaction; Photochemotherapy; Photosensitizing Agents; Remission Induction; Scalp; Sunlight

Topical photodynamic therapy (PDT) is an approved treatment for actinic keratosis (AK). To enhance the efficacy of PDT for AKs, physical and chemical pretreatments have been suggested.. To compare the efficacy and safety of the combination of topical calcipotriol (CAL) before methyl aminolaevulinate (MAL)-PDT for AKs of the scalp vs. conventional MAL-PDT in a randomized controlled clinical trial.. Twenty patients with multiple AKs on the scalp were randomized to receive conventional MAL-PDT with previous curettage on one side of the scalp and CAL-assisted MAL-PDT once a day for 15 days before illumination on the other side. After 3 months, patients were evaluated for clearance of AKs, side-effects and histopathology before and after the procedure. Protoporphyrin IX (PpIX) fluorescence was measured before and after illumination on both sides.. All 20 patients completed the study. Overall AK clearance rates were 92·1% and 82·0% for CAL-PDT and conventional PDT, respectively (P < 0·001). Grade 1 AKs showed similar response rates for both sides (P = 0·055). However, grade II AKs showed more improvement on the CAL-PDT side (90%) than on the MAL-PDT side (63%) (P < 0·001). Before illumination, PpIX fluorescence intensity was higher on the CAL-assisted side (P = 0·048). The treatment was more painful on the CAL-PDT side, although well tolerated. The mean visual analogue scale score was 5·4 ± 1·4 on the CAL-PDT side and 4·0 ± 0·69 on the conventional MAL-PDT side (P = 0·001). Side-effects such as erythema (P = 0·019), oedema (P = 0·002) and crusts (P < 0·001) were more pronounced on the CAL-assisted side. Histopathological analyses were obtained from five patients and both sides showed improved keratinocyte atypia following PDT, with slightly more improvement on the CAL-assisted side.. CAL-assisted PDT proved to be safe and more effective than conventional MAL-PDT for the treatment of AKs on the scalp. CAL pretreatment increased PpIX accumulation within the skin and may have enhanced the efficacy in this first human trial.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Calcitriol; Dermatologic Agents; Drug Therapy, Combination; Follow-Up Studies; Humans; Keratosis, Actinic; Male; Middle Aged; Pain; Pain Measurement; Photochemotherapy; Photosensitizing Agents; Scalp Dermatoses; Skin; Treatment Outcome

Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis.. The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed.. Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked CD4+ T cell infiltration, which peaked on days 10-11 after treatment, without pain, crusting, or ulceration.. Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a CD4+ T cell-mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs.. ClinicalTrials.gov NCT02019355.. Not applicable (investigator-initiated clinical trial).

Topics: Administration, Topical; Aged; Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols; Calcitriol; Carcinoma, Squamous Cell; CD4-Positive T-Lymphocytes; Cytokines; Female; Fluorouracil; Humans; Immunity, Cellular; Keratosis, Actinic; Male; Mice; Mice, Transgenic; Middle Aged; Precancerous Conditions; Skin Neoplasms; Thymic Stromal Lymphopoietin

Recent research demonstrated that vitamin D, apart from calcium-related actions, has antiproliferative, prodifferentia-tive and immunomodulatory activities.. To determine whether actinic keratoses may benefit from the antiproliferative and prodifferentiative effects of topical vitamin D.. The study was an investigator-blinded, half-side comparison trial. Patients applied calcipotriol cream to one side and Ultrabase cream as placebo to the other side of the scalp and/or face for 12 weeks. The total number of actinic keratoses (AKs), diameters and total scores of the target lesions were determined at each visit.. Nine patients were included, eight of whom completed the treatment. There was a statistically significant difference between the total number of AKs at baseline and at week 12 on calcipotriol applied side whereas no difference was detected on placebo applied side (p = 0.028 vs p = 1.00). The mean total score of the target lesions reduced significantly at week 12 on calcipotriol side; however, no significant reduction was found on placebo side (p = 0.017 vs p = 0.056). Although side effects were more common on calcipotriol side, the difference was not statistically significant.. Topical calcipotriol may show promise in the treatment of actinic keratoses. More studies are needed to confirm its efficacy.

Topics: Administration, Topical; Aged; Aged, 80 and over; Calcitriol; Dermatologic Agents; Drug Administration Schedule; Female; Humans; Keratosis, Actinic; Male; Middle Aged; Single-Blind Method

Topics: Calcitriol; Combined Modality Therapy; Fluorouracil; Humans; Keratosis, Actinic

Topics: Calcitriol; Cryotherapy; Dermatologic Agents; Drug Administration Schedule; Fluorouracil; Humans; Immunosuppressive Agents; Keratosis, Actinic; Retrospective Studies; Skin Cream; Treatment Outcome

Porokeratosis is defined as a disorder of keratinization characterized by one or more atrophic patches surrounded by a clinically and histologically distinctive hyperkeratotic ridgelike border called the cornoid lamella. Lesions are most commonly located on the sun-exposed sides of trunk and extremities, while exclusive facial involvement has been also reported. Despite that the exact risk of cutaneous malignancy developing in porokeratosis is unknown, it is confirmed by series of case reports, including squamous cell carcinoma, basal cell carcinoma and even melanoma. Although no definite cure exists, a number of treatment modalities, from topical medications to laser and light devices, have been reported with variable success. Although promising, reports of disseminated superficial actinic porokeratosis treated with vitamin D3 analogs are rare. No satisfactory enough effect is obtained also with calcipotriol monotherapy.We report a case of disseminated superficial actinic porokeratosis in a 80-year-old female patient, successfully treated with combination of topical calcipotriol/betamethasone gel. A significant improvement was noticed after 3 weeks; almost full resolution of the clinical symptoms without appearance of fresh lesions was achieved in the second month. To the best of our knowledge, this is the first report of successful treatment with full resolution in a short interval, by simultaneous application of vitamin D3 analog (calcipotriol) and corticosteroid (betamethasone), combined in a one commercial product as a gel for treatment of keratinocyte proliferation's disorder such as psoriasis vulgaris. This promising new entity seems to be more effective, because of the simultaneous synergetic effects of the substations, namely the normalization of the proliferation of the keratinocytes by calcipotriol on one hand, and the reducing of the inflammation by the corticosteroid on another. Sun protection stays always mandatory, as well as the regular clinical observation, regarding the risk of malignant transformation.

Topics: Administration, Topical; Aged, 80 and over; Betamethasone; Calcitriol; Drug Administration Schedule; Drug Therapy, Combination; Female; Gels; Humans; Keratosis, Actinic; Leg Dermatoses; Porokeratosis; Treatment Outcome