Library

Notes: Background  Metastatic melanoma shows different local response rates in organs to systemic or local treatment modalities. Whereas skin, soft tissue, lymph node and lung metastases seem to have better local response rates, the local response of metastases localized in the liver, brain and bone seems to be low.Objectives  The organ-specific response rate, local response rate of each therapeutic measure and survival of 68 patients with stage IV disease were evaluated.Methods  Four hundred and ten treatment periods (1–18 per patient) in 17 different organs of 43 men and 25 women (mean age 55 years, range 19–79) with measurable, widespread, surgically incurable disease were analysed. Chemotherapy was given in 405 of 410 treatment periods with dacarbazine, fotemustine, vindesine, carboplatin and temozolomide in different schedules. Local treatment modalities comprising radiotherapy, gamma knife radiosurgery and local hyperthermia were given in 71 of 410 treatment periods.Results  Local response (complete or partial local remission) was achieved in 52 treatment periods (12·7%). When local treatment modalities, either combined with systemic therapy or not, were compared with systemic therapeutic modalities alone, a local response of 24% was achieved with local measures, compared with 10% in systemic treatment only (P = 0·003). When a spontaneous remission rate of less than 5% is considered, however, local as well as systemic treatments had a significant effect (P 〈 0·001). Organ-specific response rates to local therapies showed no statistically significant differences between the various organs involved. When systemic treatments without local measures were taken into account, lung metastases, cutaneous/subcutaneous metastases and adrenal metastases performed significantly better than liver metastases. When different treatment modalities were considered, there was no significant difference between the three local measures applied (radiotherapy, gamma knife radiosurgery and hyperthermia). Among the systemic therapies, dacarbazine high dose and carboplatin monochemotherapy were superior to combined regimens using fotemustine. A local response, irrespective of the mode of therapy, was significantly associated with longer survival (median 16 months) compared with no local response or local progressive disease (median 7 months; P 〈 0·0001). When the first treatment period of each patient was considered, local response was no longer a significant predictor.Conclusions  The study shows that local therapeutic measures are superior in inducing a local response than systemic therapies alone. Induction of remission may be associated with longer survival. Chemotherapy, despite limited local response rates, is still statistically superior to an estimated spontaneous remission rate.

Notes: Background  A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-α2b 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-α2b 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-α2b 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-α2b 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-α2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.

Notes: Background Melanoma in situ (MIS) occurs on various body sites, in various age groups, and is managed by a variety of treatment modalities. Despite early treatment, recurrences may be encountered. Objectives To evaluate the influence of sex, age, body site and treatment modalities on recurrence rate in MIS. Methods Histologically confirmed cases of MIS from our dermatopathological database (n = 1351) from 1990 to 2000 were statistically analysed with respect to epidemiological characteristics, treatment modalities and outcome. Treatment modalities of the included MIS were evaluated by searching for data in the medical records and histopathological data sheets. Results There was a predominance of female patients (60·8%), and of involvement of the head and neck (53·4%). Total excision was performed in 95·9% of all patients; the remainder received cryotherapy, laser therapy or radiotherapy. In 265 patients, no data on definitive treatment were available. Alternatives to total excision were particularly performed in patients with advanced age and with lesions localized on the face. The mean ± SD 5-year recurrence rate was 6·8 ± 1·3% for surgically removed lesions, but was 31·3 ± 8·5% for lesions treated by other modalities (log rank test: P 〈 0·0001). In a multivariate approach, mode of therapy and site of involvement, but not age, were significant prognostic variables (Cox proportional hazard model: P 〈 0·01). Conclusions In MIS, treatment modalities other than surgical excision may be used in certain situations, but carry a significantly increased risk of local recurrence.