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.

[Atypical granuloma anulare in diabetes mellitus with iatrogenic hyperinsulinism]. / Atypisches Granuloma anulare bei Diabetes mellitus mit iatrogenem Hyperinsulinismus.

A remarkable case of disseminated granuloma anulare giganteum and Type-II-Diabetes mellitus with iatrogenic hyperinsulinism is described. The probable aetiopathogenic association between granuloma anulare and diabetes mellitus in this case is emphasized.

[Clinical variety of granuloma anulare]. / Zur klinischen Vielfalt des Granuloma anulare.

On the basis of over 100 cases of histologically verified granuloma anulare, we made an attempt to classify its many clinical variants. A principal distinction must be made between clinically typical and atypical forms on the one hand, and between localized and disseminated or generalized forms on the other. The various clinical pictures of the atypical forms are systematisized and described.

[Paraneoplastic lichen ruber pemphigoides]. / Zum paraneoplastischen Lichen ruber pemphigoides.

Until now, the designation "Lichen planus vesiculosus" respectively "Lichen planus pemphigoides" comprises a group of apparently very heterogenous "vesicular" variants of Lichen planus. A case is described in which both subepidermal vesicles within Lichen planus-papules and acantholytic suprabasal vesicles in normal skin areas occur simultaneously. The coexistence of "Lichen planus vesiculosus" and a Pemphigus vulgaris-like eruption without pemphigus-autoantibodies is assumed. These symptoms proved to be paraneoplastic phenomena, with an underlying hemangiopericytoma. The pathogenesis of the skin changes is presumed to rest on an autoimmune mechanism. The apparently regular retroperitoneal (pararenal, paravertebral) tumor localization in cases of paraneoplastic Lichen planus vesiculosus respectively pemphigoides is pointed out.

[Notes about cutis verticis gyrata (author's transl)]. / Zum Krankheitsbild der Cutis verticis gyrata.

A case of so-called, "Pseudo"-Cutis verticis gyrata naevocellularis is described. The possible malignant degeneration of this disease, which can also be described as "cerebriform intradermal nevus" is discussed. In this context, a classification of the "Cutis verticis gyrata" is suggested.

[Possible relations between Reiter's disease and psoriasis (author's transl)]. / Uber mögliche Beziehungen zwischen Morbus Reiter und Psoriasis.

Description of a characteristic venereal type of Reiter's disease with a pustular exanthem and a balanitis circinata. In the course of the disease the pustular exanthem probably transformed into a typical Psoriasis vulgaris. In search of genetical markers it was not possible in this case to show the HLA-antigens, which are characteristic of the Reiter's disease and the Psoriasis vulgaris; the HLA-antigens A 10, B7 and B12 however could be proved. The question is up for discussion, wether a HLA-B 27-negative Reiter's disease might include a disposition to the appearance of a phenotypical Psoriasis vulgaris, the genotype of which is represented by rather "unusual" histocompatibility-gens.

Psoriasis: odd varieties in the adult.

Occasionally we observe particular varieties of psoriasis and in rare cases transitional features with other diseases, which pose problems concerning the differential diagnosis and the nosological classification. This communication deals with the following clinical and histological aspects of psoriasis: 1) Sebopsoriasis. Relationship of psoriasis to pityriasis rubra pilaris. 2) Erythema annulare centrifugum type of psoriasis. 3) Is subcorneal pustular dermatosis an expression of pustular psoriasis? 4) Salient histopathological criteria for the diagnosis of the different atypical forms of psoriasis. 5) Presentation of an unusal case with striated and retiform verrucous psoriasis-like eruptions, which show a relationship to parakeratosis variegata.