{"entity":{"id":"mal-pdt-imiquimod-fluorouracil-superficial-bcc","kind":"trial","name":"Photodynamic therapy against imiquimod against fluorouracil for superficial basal cell carcinoma","aka":["Arits trial","Dutch superficial basal cell carcinoma trial","MAL-PDT versus imiquimod versus fluorouracil"],"tldr":"This trial compared the three non-surgical treatments people are actually offered for a thin basal cell carcinoma. Photodynamic therapy, the one that was assumed to be best, came last. The imiquimod cream was the best of the three at one year and still the best at five, though by then a fifth of those treated with it had the tumour back.","summary":"Seven Dutch hospitals randomised 601 patients with a histologically proven superficial basal cell carcinoma to methyl aminolevulinate photodynamic therapy, imiquimod cream or fluorouracil cream between 2008 and 2010, with a single blinded observer. Photodynamic therapy was the assumed best treatment and was made the comparator; the trial tested whether the two creams were non-inferior to it within 10 per cent.\n\nAt twelve months the proportion free of tumour at both three and twelve months was 72.8 per cent for photodynamic therapy (95 per cent confidence interval 66.8 to 79.4), 83.4 per cent for imiquimod (78.2 to 88.9) and 80.1 per cent for fluorouracil (74.7 to 85.9). Fluorouracil was non-inferior and imiquimod was superior: the difference against photodynamic therapy was 10.6 percentage points for imiquimod (1.5 to 19.5, p=0.021) and 7.3 points for fluorouracil (-1.9 to 16.5, p=0.120).\n\nThe five-year report is the one to quote, because it separates the two creams from each other. Tumour-free survival at five years was 62.7 per cent after photodynamic therapy (55.3 to 69.2), 80.5 per cent after imiquimod (74.0 to 85.6) and 70.0 per cent after fluorouracil (62.9 to 76.0). Against photodynamic therapy the hazard ratio for treatment failure was 0.48 for imiquimod (0.32 to 0.71, p<0.001) and 0.74 for fluorouracil (0.53 to 1.05, p=0.09); imiquimod also beat fluorouracil, hazard ratio 0.65 (0.43 to 0.98, p=0.04).\n\nThe side effects differ in kind rather than in amount. Moderate to severe pain and burning were reported during the photodynamic therapy session itself; the creams caused swelling, erosion, crusting and itching over weeks. In a separate analysis alongside the trial, twelve-month costs were 680 euros for photodynamic therapy, 526 for imiquimod and 388 for fluorouracil, so the most expensive treatment was also the least effective.","status":"positive","asOf":"2026-09-25","links":[{"label":"ISRCTN79701845","url":"https://www.isrctn.com/ISRCTN79701845"},{"label":"One-year results (Lancet Oncology 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70143-8"},{"label":"Five-year results (Journal of Investigative Dermatology 2018)","url":"https://doi.org/10.1016/j.jid.2017.09.033"},{"label":"Five-year results on PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29045820/"}],"tags":[],"related":[],"cancers":["basal-cell-carcinoma","skin-cancer"],"sections":[],"technologies":["photodynamic-therapy-lasers"],"targets":[],"drugs":["imiquimod","fluorouracil","aminolevulinic-acid"],"companies":[],"institutions":[],"pathways":[],"terms":["topical-and-destructive-treatment-bcc"],"trials":["sins-trial","mal-pdt-versus-surgery-nodular-bcc","mal-pdt-versus-cryotherapy-superficial-bcc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"ISRCTN79701845","phase":"3","setting":"Histologically proven primary superficial basal cell carcinoma: methyl aminolevulinate photodynamic therapy in two sessions a week apart, against imiquimod 5 per cent cream once daily five days a week for six weeks, against fluorouracil 5 per cent cream twice daily for four weeks, with freedom from tumour at both three and twelve months as the primary outcome and a non-inferiority margin of 10 per cent","sponsor":"Maastricht University Medical Centre, funded by the Netherlands Organisation for Scientific Research","result":"Tumour-free survival at five years 80.5 per cent with imiquimod, 70.0 per cent with fluorouracil and 62.7 per cent with methyl aminolevulinate photodynamic therapy; imiquimod beat both (hazard ratio 0.48 against photodynamic therapy and 0.65 against fluorouracil).","yearReported":2018,"enrolled":601,"enrolledBasis":"randomised","enrolledNote":"601 patients were randomised at seven Dutch hospitals between March 2008 and August 2010: 202 to photodynamic therapy, 198 to imiquimod and 201 to fluorouracil. The ISRCTN record carries no enrolment figure.","outcomes":[{"endpoint":"Tumour-free survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Imiquimod 5 per cent cream","value":80.5,"note":"95 per cent confidence interval 74.0 to 85.6"},{"name":"Fluorouracil 5 per cent cream","value":70,"note":"95 per cent confidence interval 62.9 to 76.0"},{"name":"Methyl aminolevulinate photodynamic therapy","value":62.7,"note":"95 per cent confidence interval 55.3 to 69.2"}],"source":"https://doi.org/10.1016/j.jid.2017.09.033"},{"endpoint":"Free of tumour at both 3 and 12 months","primary":true,"unit":"%","arms":[{"name":"Imiquimod 5 per cent cream","n":189,"value":83.4,"note":"95 per cent confidence interval 78.2 to 88.9"},{"name":"Fluorouracil 5 per cent cream","n":198,"value":80.1,"note":"95 per cent confidence interval 74.7 to 85.9"},{"name":"Methyl aminolevulinate photodynamic therapy","n":196,"value":72.8,"note":"95 per cent confidence interval 66.8 to 79.4"}],"source":"https://doi.org/10.1016/s1470-2045(13)70143-8"},{"endpoint":"Hazard ratio for treatment failure at 5 years against photodynamic therapy","unit":"hazard ratio","arms":[{"name":"Imiquimod 5 per cent cream","value":0.48,"note":"95 per cent confidence interval 0.32 to 0.71, p<0.001"},{"name":"Fluorouracil 5 per cent cream","value":0.74,"note":"95 per cent confidence interval 0.53 to 1.05, p=0.09"}],"source":"https://doi.org/10.1016/j.jid.2017.09.033"}],"replication":"SINS reached the same conclusion about imiquimod from the other direction, comparing it with surgery rather than with the other non-surgical options, and found it inferior to the operation."},"route":"/trials/mal-pdt-imiquimod-fluorouracil-superficial-bcc/","neighbours":{"cancer":[{"id":"basal-cell-carcinoma","kind":"cancer","name":"Basal cell carcinoma","route":"/cancers/basal-cell-carcinoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"technology":[{"id":"photodynamic-therapy-lasers","kind":"technology","name":"Photodynamic therapy lasers and light sources","route":"/technologies/photodynamic-therapy-lasers/"}],"drug":[{"id":"aminolevulinic-acid","kind":"drug","name":"Aminolevulinic acid (topical, for photodynamic therapy)","route":"/drugs/aminolevulinic-acid/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"imiquimod","kind":"drug","name":"Imiquimod","route":"/drugs/imiquimod/"}],"term":[{"id":"topical-and-destructive-treatment-bcc","kind":"term","name":"Creams, light and cold for basal cell carcinoma","route":"/terms/topical-and-destructive-treatment-bcc/"}],"trial":[{"id":"mal-pdt-versus-cryotherapy-superficial-bcc","kind":"trial","name":"Photodynamic therapy against cryotherapy for superficial basal cell carcinoma","route":"/trials/mal-pdt-versus-cryotherapy-superficial-bcc/"},{"id":"mal-pdt-versus-surgery-nodular-bcc","kind":"trial","name":"Photodynamic therapy against surgery for nodular basal cell carcinoma","route":"/trials/mal-pdt-versus-surgery-nodular-bcc/"},{"id":"scin-trial","kind":"trial","name":"SCIN (curettage then imiquimod against excision for nodular basal cell carcinoma)","route":"/trials/scin-trial/"},{"id":"sins-trial","kind":"trial","name":"SINS (surgical excision against imiquimod cream for basal cell carcinoma)","route":"/trials/sins-trial/"}]}}