Topical Therapy

Early studies investigating topical tretinoin's role in skin cancer chemopreven-tion yielded conflicting results, although human trials beginning in 1962 have consistently shown mild to moderate reductions in the number of AKs.25,33-42 Bollag and Ott found a 50 to 100% reduction in AKs in 44 of 51 patients treated with tretinoin; however, recurrence of AKs was noted within a year following cessation of therapy.43 In vitro studies have shown that tretinoin induces pro-apop-totic pathways in keratinocytes following UVB-radiation, suggesting a possible preventive mechanism for the development of NMSCs.38 Topical tretinoin treatment has also been shown to block NFkB signaling after UVB, another mechanism by which tumor promotion

May be slowed.44,45

Additional human studies have looked at whether topical tretinoin prevents the development of invasive malignancies. Renal transplant patients receiving topical tretinoin developed fewer SCCs than those treated with placebo.46 Dysplastic nevi treated with topical tretinoin under occlusion and histologically confirmed to be dysplastic nevi prior to treatment were observed to undergo both clinical and histologic regression.47,48 Furthermore, cytologic atypia that had been noted prior to treatment disappeared and the nevi contained benign-appearing melanocytes.47 Meyskens et al. evaluated three patients with biopsy-proven dysplastic nevi, two with personal histories of melanoma, and the third with a strong family history of melanoma.49 Following 10 to12-week treatment regimens with topical tretinoin 0.05% under occlusion, posttreatment biopsies of the dysplastic nevi showed either complete conversion to benign features (two patients) or regression to minimal dysplasia. A fourth study treated dysplastic nevi with tretinoin, tretinoin with hydrocortisone 1% cream, or placebo. No histologic evaluations were done prior to treatment, but statistically significant clinical regression was noted in both groups of patients receiving tretinoin but not in patients receiving placebo. At the conclusion of the study, however, histologic evaluations showed no difference in the histologic atypia of nevi among the three treatment groups.50

Adapalene has been used in only one study to treat AKs. In a multicenter, investigator-blinded, randomized study, Kang et al. found that both 0.1 and 0.3% adapalene gel improved AKs when compared to placebo.51 Approximately 65% of patients treated with either strength adapalene experienced marked or moderate improvement in AKs compared with only 34% of the vehicle control patients.51

Tazarotene is a synthetic retinoid that is Food and Drug Administration (FDA)-approved for the topical treatment of acne and psoriasis.52-54 Tazarotene 0.1% gel regularly applied for 5 to 8 months has been reported to successfully treat BCCs and SCCs in situ, likely via inducing tumor suppressor genes that are underexpressed in BCCs and SCCs in sun-exposed skin, and initiating pro-apoptotic pathways and decreasing pro-liferation.55-59 In PTCH gene heterozygote mice treated with UV and ionizing radiation, tazarotene has been shown to inhibit the development of BCCs.60 However, few studies have been conducted using tazarotene on human malignancies, with one study reporting complete regression without recurrence to be 30.5% at 3-year follow-up without recurrence.61

Topical retinoids, with their limited side effects profile and reasonable overall tolerability (see Table 53-3), remain an interesting group of chemopreventive agents. Unfortunately, the paranoia of third-party insurers that patients will benefit cosmetically from use of these agents62-66 appears to preclude their coverage for the indication of skin cancer chemoprevention, greatly disincentivis-ing patients from this approach.

  • Contact
  • Category: Cancer