Temozolomide and interferon alpha 2b in metastatic melanoma stage IV.

BACKGROUND: A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV. OBJECTIVES: The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented. PATIENTS/METHODS: Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day. RESULTS: We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths. CONCLUSIONS: The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.

Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group.

PURPOSE: Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS: In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS: Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION: Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.

Anti-inflammatory efficacy of low-dose cyclosporin A in psoriatic arthritis. A prospective multicentre study.

Fifty-five patients with psoriatic arthritis were treated with a low dose of cyclosporin A (CyA) (mean dose 2.7 mg/kg per day) for a period of 6 months to investigate the efficacy of CyA on disease parameters. Significant improvement in the joint complaints and inflammation parameters was observed including a decrease in the number of painful (-46%) and swollen (-45%) joints, tenderness (Ritchie Index: -50%) and degree of swelling (-46%), patient's assessment of pain (-35%), the duration of morning joint stiffness (-37%), as well as a decrease in C-reactive protein (-52%). A 50% reduction of joint complaints required a total of 24 weeks, whereas a 50% reduction of skin involvement was achieved after 5-6 weeks of treatment. Four patients left the study due to adverse events: creatinine level increase in two patients, hypertension in one patient and gastroenteritis in the fourth patient. Joint scintigraphy in 18 patients indicated an improvement or stable condition in 61% of cases after a mean follow-up of approximately 8 months. The results of this prospective study show that low-dose CyA effectively improves not only skin lesions, but also joint complaints in psoriatic arthritis.

[The tromantadine contact eczema]. / Das Tromantadinkontaktekzem.

Tromantadinhydrochlorid has been established as a local antiviral substance in the treatment of recurrent herpes. With longer duration of treatment contact allergy can be observed. In our own material we noticed this in 26 of 387 treated patients.

[A preliminary report of "selective ultraviolet phototherapy" in psoriasis (author's transl)]. / Erste Erfahungen mit der "selektiven ultravioletten phototherapie" (SUP) bei der Behandlung der Psoriasis vulgaris.

35 patients with psoriasis were treated solely by UV irradiation using a Saalmann selective ultraviolet phototherapy lamp (SUP), a mercury lamp with increased emission between 310 and 320 nm. Irradiation four to five times weekly produced 90 to 100% improvement in 83% of the patients. Nineteen of the thus-treated patients showed complete clearing of the psoriatic lesions. The average duration of treatment was 4 weeks. These good results were maintained on a regimen of twice-weekly UV therapy.

[Photoallergy: results of photo patch testing in dermatological patients (author's transl)]. / Photoallergie: Der Nachweis durch den belichteten Epikutantest in einem dermatologischen Krankengut

150 patients with light sensitivity of unknown aetiology were photo patch tested at the 2nd Department of Dermatology University of Vienna. 22 patients showed photoallergy. The identified photoallergens were mostly halogenated salicylanilides and other phenolic compounds. These substances are used as antimicrobials in soaps and cosmetics and as antimycotics in dermatological preparations. Four of the patients showed allergic contact photosensitivity to chlorpromazine. In two patients a new photoallergen has, perhaps, been discovered, namely a derivative of phthalic acid which is employed as fungicidal pesticide. The problems and consequences of photoallergy are discussed.

Specific and total serum IgE measurements in the diagnosis of penicillin allergy. A long term follow-up study.

Sera from 204 patients with acute or former reactions following penicillin treatment were investigated by RAST with specificity for benzylpenicilloyl and phenoxymethyl-penicilloyl. The IgE antibody levels were followed up for of more than 2 years. Positive results could be observed at the time of the acute reactions and the weeks following; later months or years in many cases. Occasionally negative RAST results occurred within 30 days; on the other hand high levels of specific IgE persisted for years in some patients. Total serum IgE measured by RIST and the RAST results showed similar patterns, with mean levels of 568 u/ml between 0 and 30 days after the penicillin allergic reaction, 286 u/ml between 30 days and 1 year, and 195 u/ml in cases after 1 year corresponded well with the observed decline in specific IgE. Skin tests performed with penicilloyl-polylysine in 118 patients showed an overall correlation of 91-5% with the RAST results. Differences between the two test systems were observed in patients with a long interval between the test and the last allergic attack. None of the patients with proved penicillin allergy had atopic diseases or a history of atopy. On the basis of these findings it is suggested that the determination of both circulating specific IgE and total IgE should be of great value for diagnostic purposes during acute drug reactions and in the months immediately afterwards.

Contact dermatitis from tromantadine hydrochloride.

Of 240 patients treated with 1% tromantadine hydrochloride ointment, 20 showed local irritation, of which 12 were due to contact allergy as demonstrated by patch testing.

[The local treatment of the keratoacanthoma with 5-fluorouracil]. / Lokalbehandlung des Keratoakanthoms mit 5-Fluoruracil

In the last two years thirteen patients with keratoacanthomas were treated with 5% f-fluorouracil ointment at the Department of Dermatology II of the University of Vienna. Treatment lasted from two to eight weeks depending upon the size of the tumor. In all cases there was clearing of lesions with good cosmetic results. During an average follow-up period of 7.4 months for all patients there was no recurrence of the tumors.

Vitamin A acid in lichen planus.

Since 1971, Vitamin A acid (VAA) has been used for topical treatment of lichen planus (L.p.) at the 2nd Department of Dermatology in Vienna. During this period, 43 patients have been treated in the following way: for a period up to 3 weeks, a 0.05% or 0.1% VAA cream or solution was applied twice daily to the affected skin or mucosa. In the first days of this therapy, a characteristic local reaction of the L.p. lesions could be observed; first an edematous swelling appeared, followed by scaling and regression of efflorescences. Finally, an inflammatory skin reaction also developed. At this juncture, VAA was abandoned and the treatment was continued with steroid-containing ointments. Occlusive dressings were used only in cases of hypertrophic L.p. The same therapy was performed in L.p. of mucous membranes. By this method it was possible to achieve good therapeutical results in all treated cases. However, the frequency of recurrences of L.p. could not be diminished.