Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma.

PURPOSE: Some phase II studies have suggested that the combination of interferons (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM) increases the antitumor activity of DTIC alone. In an attempt to confirm this hypothesis, a randomized study was performed with the further intent of observing whether low doses of recombinant interferon alfa-2a (rIFN alpha 2a) could be as effective as intermediate doses. PATIENTS AND METHODS: Two hundred sixty-six patients were randomized onto three different treatment arms: DTIC 800 mg/m2 intravenously (IV) days 1 and 21; DTIC plus rIFN alpha 2a 9 mIU intramuscularly (IM) daily; and DTIC plus rIFN alpha 2a 3 mIU IM three times per week. Major prognostic factors were well balanced among the three arms. Chemotherapy was administered for a maximum of eight cycles. After 6 months of therapy, rIFN alpha 2a was continued until disease progression at 3 mIU three times per week in responding patients who had received the combined treatment. RESULTS: The percentage of objective responses did not differ among the three groups (20%, 28%, and 23%, respectively), although a significant prolongation of response duration was observed when rIFN alpha 2a was added to DTIC (2.6 v 8.4 v 5.5 months, respectively). However, this improvement in response duration did not translate into an amelioration of overall survival. The addition of rIFN alpha 2a led to the onset of flu-like syndrome, but in no case was it necessary to withdraw the treatment program and no toxic deaths or life-threatening toxicities were reported. CONCLUSION: In this study, rIFN alpha 2a significantly prolonged response duration, whereas no effects on response rate and survival were observed; rIFN alpha 2a 3 mIU appeared to be equally effective and better tolerated than 9 mIU.

Economic evaluation of an educational campaign for early diagnosis of cutaneous melanoma.

Public educational campaigns for the early diagnosis of cutaneous melanoma are considered an effective approach in the prevention of this disease, since they increase the number of cases detected early and consequently lengthen patients' life expectancy. We performed an economic evaluation of such a campaign in Bergamo, Italy, in order to quantify its costs and consequences. We used cost-effectiveness analysis to compare the costs and effects of the campaign with those of the 'do nothing' option. The analysis was performed from the perspective of the Italian National Health Service [the Servizio Sanitario Nazionale (SSN)]. Accordingly, only direct costs related to publicly financed healthcare services were considered. No indirect costs or benefits were considered because they are not relevant to the SSN. Incremental analysis was used to obtain results in terms of additional costs per life-year saved (LYS). Overall LYS were quantified by comparing the survival curves for 4 subgroups of patients with different lesional thicknesses at diagnosis ( < 0.76mm, 0.76 to 1.50mm, 1.51 to 3.00mm and > 3.00mm). All costs were estimated in 1993 Italian lire (L). Overall effectiveness amounted to 233.49 LYS. Using a 5% discount rate, the value of effectiveness was 171.3 LYS. The total cost of the educational campaign (i.e. the sum of the organisational and 'induced' costs minus the costs saved) was estimated at L817 million (approximate 1993 exchange rate $US1 = L1573), and L905 million after discounting at a rate of 5%. Thus, using discounted cost and effectiveness data, the cost of the educational campaign was L5.28 million per LYS.

[Blue nevus of the uterine cervix]. / Il nevo blu della cervice uterina.

Seven cases of blue nevus of the endocervix were examined macroscopically and histologically. The endocervical blue nevus is a rare lesion which can be incidentally found in surgical pieces after hysterectomy in middle-aged women. It looks like a blue-blackish little lesion, located superficially in the submucosa of the endocervix. The immunohistochemical results are positive for Protein S100 of the nevus cells. Due of its localization in the cervical duct the lesion can be hardly identified through colposcopy. Histogenetical hypotheses are finally discussed.

[Metastatic malignant melanoma of the ovary]. / Melanoma maligno metastatico dell'ovaio.

We report 2 cases of ovarian metastases of malignant melanoma arisen 4 and 6 years after the removal of the primitive epithelial neoplasia. In both cases the ovarian neoplasia was unilateral. Both the macroscopic and the histological aspects of the malignant melanoma were examined. From both cases it was clear that it was a solid neoplasia with histological aspect of wide epithelioid cells with abundant cytoplasm and intracytoplasmatic melanotic pigment. The immunohistochemical results supported positivity for protein S100, vimentine and HMB45, negativity for cytokeratine.

[Epithelial changes associated with invasive epidermoid carcinoma of the vulva]. / Alterazioni epiteliali associate al carcinoma epidermoide invasivo della vulva.

The frequency and meaning of epithelial alterations adjacent to a vulvar invasive carcinoma are examined. In the period from 1986 to 1989, 37 cases of vulvar invasive carcinoma were observed in the Bergamo Hospital (Anatomopathology Institute of Bergamo) in women aged between 54-95 years operated for vulvectomy. The vulvar epithelium adjacent to the invasive carcinoma was studied in order to determine the frequency and the type of associated lesions. Two lesions seem to be meaningfully correlated to the vulvar carcinoma: the lichen sclerosus in 59% of cases and the VIN3 of differentiated type in 35%. The identification of these epithelial lesions can serve to select the cases with increased risk to develop invasive carcinoma.

Cutaneous malignant melanoma appearing during photochemotherapy of mycosis fungoides.

We report a case of malignant melanoma that appeared in a 56-year-old man with mycosis fungoides (stage Ia) during treatment with PUVA. The cumulative UVA dose was 1,177 J/cm2. The pigmented lesion was removed and PUVA therapy discontinued. Histological examination revealed a superficial spreading malignant melanoma (1.77 mm thick, Clark level IV). The delayed-type cutaneous hypersensitivity was studied. The presence of a second malignancy after mycosis fungoides and PUVA therapy may have been coincidental. Nevertheless, this case suggests that the immunosuppression induced by mycosis fungoides and by PUVA therapy might be a pathogenetic factor in the development of malignant melanoma.

Combined Clark's nevus.

We report five cases of combined Clark's nevi. Like all melanocytic nevi, Clark's nevus can combine with other nevi to produce lesions that are hard to interpret clinically and histologically. The morphology of combined Clark's nevus can resemble that of a melanoma associated with a nevus.

Long-term follow-up of dermatitis herpetiformis in children.

Dermatitis herpetiformis was diagnosed in seventy-six children by its clinical features and by detection of granular IgA deposits in the papillary dermis of perilesional skin. Enteric alterations demonstrated by measurement of D-xylose absorption and by small intestinal biopsies were detected in over 90% of all patients. A complete follow-up was obtained for all children who were followed for 3 to 10 years. Treatment with a gluten-free diet alone led to a reversal of the intestinal abnormality in 100% of our children and to the disappearance of cutaneous lesions in 82% of reported cases. This suggests that a complete remission of symptoms can be obtained with a gluten-free diet alone. Dapsone alone is effective therapy for the rash but does not affect the intestinal alterations. Furthermore, the lack of side effects to dietetic therapy for a long period of time makes the diet the treatment of choice in this disease.