Tretinoin cream 0.02% for the treatment of photodamaged facial skin: a review of 2 double-blind clinical studies.

In extensive clinical studies and practical use since its US Food and Drug Administration approval in 1995, tretinoin emollient cream 0.05% has been shown to be safe and effective in the treatment of fine facial wrinkles, mottled hyperpigmentation, and skin roughness. To provide additional prescribing flexibility for various patient needs, a new lower concentration formulation, tretinoin cream 0.02% was chosen for further development. Two multicenter, randomized, double-blind, vehicle-controlled clinical., studies were conducted to evaluate the safety and efficacy of the lower concentration tretinoin formulation in the treatment of moderate-to-severe facial photodamage. Results indicate statistically significant improvement in fine wrinkling, coarse wrinkling, and yellowing with the use of tretinoin cream 0.02% at week-24 end point, compared with placebo. Therapy with tretinoin cream 0.02% was well tolerated overall and demonstrated a favorable safety profile. Both studies demonstrated that tretinoin cream 0.02% is safe and effective for the treatment of moderate-to-severe photodamaged facial skin.

Clindamycin phosphate 1% gel in acne vulgaris.

A 12-week study compared Clindagel, a unique water-based gel formulation of clindamycin phosphate 1%, administered once daily, and Cleocin T, a slightly different gel formulation indicated for twice-daily use, in the treatment of acne vulgaris. Clindagel was safe and effective and equivalent to Cleocin T gel, albeit with a better tolerability profile. Clindagel is a viable alternative to Cleocin T gel.

Betamethasone valerate in foam vehicle is effective with both daily and twice a day dosing: a single-blind, open-label study in the treatment of scalp psoriasis.

BACKGROUND: Psoriasis is a chronic relapsing skin disorder that affects about 2% of the U.S. population and involves the scalp approximately 50% of the time. Topical corticosteroids, including betamethasone valerate, have been used effectively in the treatment of corticosteroid-responsive dermatoses of the skin and scalp. Betamethasone valerate (BMV) in foam vehicle (Luxiq) is designed to improve patient compliance with topical therapy. Superior efficacy over a BMV lotion preparation has been demonstrated with twice-daily use. Even greater compliance would be expected if the drug is effective with once-daily application. PURPOSE: To compare the efficacy of the betamethasone valerate foam (Luxiq) in the treatment of scalp psoriasis following once-daily versus twice-daily dosing. METHODS: Seventy-nine patients with moderate to severe scalp psoriasis from seven centers were enrolled and treated with BMV foam either once a day or twice a day for four weeks. The physician-grader was blinded to the treatment regimen, and the subjects were randomly assigned to either once-daily or twice-daily dosing in a 1:1 ratio. RESULTS: The signs of psoriasis (plaque thickness, scaling, and erythema) were assessed before and after treatment. The investigator's and the patients' global assessments were also evaluated. The composite score improved from 7.7 +/- 2.1 to 3.0 +/- 2.2 with twice-a-day use and from 8.1 +/- 2.2 to 3.9 +/- 2.8 with once-daily use (p > 0.05 for the difference between groups). DISCUSSION: BMV foam is effective for scalp psoriasis with both once-a-day and twice-a-day use. This feature of the BMV foam is encouraging for expected improvement in clinical use.

A double-blind, placebo-controlled study of topical tetracaine in the treatment of herpes labialis.

BACKGROUND: Before the September 1996 approval of 1% penciclovir cream for the treatment of herpes labialis, no other prescription topical therapy was approved for the treatment of this recurrent viral disease affecting approximately 20% of the adult population of the United States. Local anesthetics, such as tetracaine, have been used in over-the-counter topical products, but are only labeled for the relief of pain and itching associated with cold sores and fever blisters. OBJECTIVE: The purpose of this study was to determine whether a topical preparation of a tetracaine cream is safe and effective in the treatment of recurrent herpes labialis in immunocompetent patients. METHODS: A double-blind, placebo-controlled study was conducted to assess the relative effectiveness and safety of 1.8% tetracaine equivalent in a cream base versus placebo in the treatment of herpes labialis in immunocompetent adults. In this study, patients applied medication up to 6 times daily until the lesions healed (scab loss), but for no more than 12 days. The patients were monitored on the day of enrollment, once during the course of treatment, and at a final visit after the lesions had healed. Patients assessed themselves the day of scab formation and the day the scab fell off. They also graded, on a daily basis, their perception of relief from itching and pain and the overall benefit. RESULTS: The results from 72 patients (35 = placebo; 37 = active) showed that scab formation occurred in a mean of 2.4 +/- 0.27 days for the placebo group and 2. 3 +/- 0.26 days for the active group. Healing time (scab loss) occurred in a mean 7.2 +/- 0.36 days for the placebo group and in 5. 1 +/- 0.35 days in the active group. The difference observed for healing time between the placebo and the active tetracaine cream was statistically significant (P =.0002). This represents an approximately 30% reduction in the healing time for the active group compared with the placebo group. In addition, the study patients ranked the benefit of their treatment on a daily basis and graded the overall benefit of the therapy at their final visit. The ranking was on a 1 to 10 index scale (1 = no benefit at all; 10 = very effective treatment). At the final visit there was a statistically significant difference in the benefit index for active preparation versus placebo for this subjective evaluation (placebo index, 5.9 +/- 0.6; active index, 7.3 +/- 0.48 [P =.0359]). The subjects also evaluated relief from itching and pain on a daily basis. Relief from itching was significantly greater in the active group than in the placebo group on days 2 and 3 after initiation of the treatment. Pain was not found to be severe in either the placebo or active treatment groups. At day 2 of treatment and beyond, pain scores never were greater than 3.2 +/- 0.28 for active on a scale in which 1.0 represented "no pain at all" and 10 represented "most severe pain imaginable." Although mean values for pain were always less for the active therapy, lesional pain scores never reached statistically significant lower values for active compared with placebo. CONCLUSION: Our findings indicate that a 1.8% topical tetracaine cream, when applied frequently, significantly reduces the healing time of recurrent herpes labialis lesions. Additionally, it is perceived by the study subjects to reduce itching of the lesions and to have a beneficial overall effect.

Intratumoral chemotherapy with fluorouracil/epinephrine injectable gel: a nonsurgical treatment of cutaneous squamous cell carcinoma.

BACKGROUND: We attempted to originate a nonsurgical treatment alternative for cutaneous squamous cell carcinoma (SCC), and we evaluated intratumoral modified-release chemotherapy with fluorouracil/epinephrine injectable gel (5-FU/epi gel). OBJECTIVE: To assess the safety and efficacy, we conducted an open-label pilot study of 5-FU/epi gel in 25 patients with biopsy-proven SCC lesions on the face, head, neck, trunk, arms, and hands. METHODS: Each tumor site was injected intradermally with up to 1.0 ml of 5-FU/epi gel. One SCC per patient was treated weekly for up to 6 weeks, then observed for 4 months at which time the tumor site and margins were excised for histologic examination. RESULTS: Overall, 96% (22 of 23) of evaluable treated tumors had histologically confirmed complete tumor clearing. No clinically significant systemic reactions or unexplained treatment-related adverse medical events occurred. The evaluations of the cosmetic appearance of the treated sites, judged subjectively by clinicians and patients, were mostly good to excellent and generally in close agreement. CONCLUSION: Treatment of superficial SCC with 5-FU/epi injectable gel results in a high rate of histologically confirmed complete tumor responses and may provide a nonsurgical treatment alternative in selected patients.

Nonsurgical treatment of basal cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable gel.

BACKGROUND: To develop a nonsurgical treatment alternative for basal cell carcinomas (BCCs), we evaluated intralesional sustained-release chemotherapy with 5-fluorouracil/epinephrine injectable gel (5-FU/epi gel). OBJECTIVE: To optimize the dose and treatment schedule, we compared the safety, tolerance, and efficacy of six treatment regimens of 5-FU/epi gel in patients with BCCs. METHODS: Two doses and four treatment schedules of 5-FU/epi gel were compared in an open-label, randomized study of 122 patients with biopsy-proven BCCs. One BCC per patient was treated for up to 4 to 6 weeks, then observed for 3 months at which time the tumor site was completely excised for histologic examination. RESULTS: Overall, 91% of evaluable treated tumors (106 of 116) in all regimens had histologically confirmed complete tumor resolution. No clinically significant treatment-related systemic adverse events occurred. The best response rate, tolerance, and patient compliance with assigned dose were in patients receiving 0.5 ml of 5-FU/epi gel three times a week for 2 weeks. The complete response rate based on histologic assessment in this group was 100%. CONCLUSION: Results demonstrate that treatment of BCC with 5-FU/epi gel is both safe and effective, may result in histologically confirmed complete response rates comparable to surgery, and provides a nonsurgical treatment alternative in selected patients.

Multicenter trial for long-term safety and efficacy comparison of 0.05% desonide and 1% hydrocortisone ointments in the treatment of atopic dermatitis in pediatric patients.

BACKGROUND: Desonide, a class 6 nonfluorinated topical corticosteroid, has been available for more than two decades. Hydrocortisone is widely used in the treatment of dermatoses in children. OBJECTIVE: Our purpose was to compare the safety and efficacy of desonide ointment and 1.0% hydrocortisone ointment in children with atopic dermatitis. METHODS: One hundred thirteen children (mean age, 4.8 years) with mild to moderate atopic dermatitis were enrolled in a multicenter, randomized, investigator-masked, parallel-group study. Treatments were applied twice daily for 5 weeks and extended to 6 months in 36 of the patients. Signs of atrophy were evaluated. Efficacy was determined by measuring global improvement, erythema, lichenification, excoriations, oozing or crusting, pruritus, and induration. RESULTS: No differences in safety were observed between hydrocortisone and desonide. The investigator's global assessment of improvement significantly favored desonide over hydrocortisone during 3 months of treatment (p < 0.05). CONCLUSION: Desonide ointment showed greater efficacy, produced more rapid improvement, and demonstrated an equivalent cutaneous safety profile when compared with 1% hydrocortisone ointment for up to 6 months.

Efficacy and safety of twice-daily augmented betamethasone dipropionate lotion versus clobetasol propionate solution in patients with moderate-to-severe scalp psoriasis.

This 2-week, randomized, multicenter, investigator-blinded, parallel-group study was conducted to compare the efficacy and safety of augmented betamethasone dipropionate 0.05% lotion and clobetasol propionate 0.05% solution in the treatment of moderate-to-severe scalp psoriasis among 197 (193 assessable) healthy adult patients with at least 20% scalp-surface involvement. The patients received one of two treatments applied twice a day for 2 weeks. Signs and symptoms were evaluated at baseline, after 3 days (day 4), and after weeks 1 (day 8) and 2 (day 15) of treatment. As early as 3 days after treatment, scaling and induration were improved significantly faster by betamethasone dipropionate than by clobetasol propionate. Both treatments also reduced erythema and pruritus. Patients receiving betamethasone dipropionate had a significantly greater mean percent improvement in total sign/symptom scores (P < or = 0.015) at all visits and better mean global clinical response scores at the early visits (days 4 and 8) (P < or = 0.017). At the end of the study, only mild disease was present in both groups. Adverse events were reported by 34.0% and 36.4% of patients receiving betamethasone dipropionate and clobetasol propionate, respectively. All events were transient, most were mild and local, and no discontinuations resulted. The effects of treatment on the hypothalamic-pituitary-adrenal axis were not measured. In conclusion, augmented betamethasone dipropionate lotion and clobetasol propionate solution were equally effective, but betamethasone dipropionate lotion provided a faster onset of relief for scaling and induration, which may enhance patient compliance and patient satisfaction with treatment.

A controlled clinical trial of a new formulation of betamethasone dipropionate cream in once-daily treatment of psoriasis.

In a multicenter, evaluator-blind, parallel group study of 244 patients with moderate to severe psoriasis, a once-daily application of a new formulation of beta-methasone dipropionate 0.05% cream, augmented formulation (AF), and a twice-daily application of fluocinonide 0.05% cream were compared, with respect to safety and efficacy. Results significantly favored betamethasone dipropionate AF over fluocinonide, as indicated by improvements in signs of erythema, induration, and scaling, as well as the physicians' and patients' global evaluations of response after 14 days of treatment. As a result of adverse experiences, treatment had to be discontinued in three patients on fluocinonide. No patient on betamethasone dipropionate AF had to discontinue treatment.

Mucha-Habermann's disease in children: treatment with erythromycin.

Safe therapeutic measures for Mucha-Habermann's disease in children are lacking. Three patients with the disease were treated with erythromycin for systemic effect. Although the series is small and uncontrolled, this approach seemed effective. An anti-inflammatory mechanism related to inhibition of chemotaxis is speculated.

Metabolic effects of human growth hormone and of estrogens in boys with Duchenne muscular dystrophy.

Metabolic balance studies were conducted in seven boys with Duchenne-type muscular dystrophy, and in six normal boys of similar age, during a 12 day control period and during a 12 day period of treatment with human growth hormone (HGH) at the following doses: 0.0168, 0.0532, and 0.168 U/kg body weight (BW)((3/4)) per day (doses A, B, and C, respectively). In five of the six normals, dose C caused positive balances in N, P, Na, and K; doses B and A had anabolic effects in two and one normal subjects, respectively. In six of the seven Duchenne cases, dose C caused negative balances of N and K, and sometimes of P. Negative balances were produced in three of the Duchenne subjects by dose B, and in one by dose A. None of the dystrophy cases exhibited an anabolic response to any dosage of HGH tested. The release of endogenous HGH in response to insulin, after 2 days' pretreatment with diethylstilbestrol, was similar in both groups of subjects. In the course of these tests, a marked anabolic effect of diethylstilbestrol in the Duchenne patients was apparent. Therefore metabolic balance studies were repeated, in both Duchenne and normal cases, during a 12 day control period and during 12 days of treatment with diethylstilbestrol (0.106 mg/kg BW((3/4)) per day). In three of the normal children, diethylstilbestrol had no effect on the elemental balances; in two cases, a retention of Na was observed. In all seven Duchenne cases, diethylstilbestrol caused positive balances in N, P, Na, and K. Ethinyl estradiol (0.0106 mg/kg BW((3/4)) per day) produced positive N, P, Na, and K balances in all three Duchenne cases tested with this agent. The data show that exogenous HGH causes a catabolic effect in boys with Duchenne dystrophy. These patients are hyperresponsive to the anabolic effect of diethylstilbestrol. The latter phenomenon may reflect the inhibitory effect of estrogen upon the peripheral actions of these boys' endogenous HGH.