[Pemetrexed-induced scleroderma-like changes in the lower legs]. / Sclérose cutanée des deux membres inférieurs sous pemetrexed.

BACKGROUND: Pemetrexed (Alimta(®)) is a new-generation antifolate used to treat malignant pleural mesothelioma and non-small cell lung cancer (NSCLC). We report two cases of a new toxicity induced by pemetrexed: scleroderma-like induration of the lower extremities. PATIENTS AND METHODS: The first case concerned a 66-year-old man diagnosed with pulmonary adenocarcinoma metastatic from the outset and in whom maintenance treatment comprised pemetrexed after first-line therapy comprising six courses of cisplatin-pemetrexed. After the fourth cycle of pemetrexed, he presented an erythematous oedema of the left leg, which was subsequently bilateral. Clinically, there was painful cellulitis associated with areas of bruising. The lesions had an appearance of erysipeloid-like infection, and there was no fever. The second case concerned a 70-year-old woman diagnosed with metastatic NSCLC. From the first course of pemetrexed, given as maintenance therapy, she presented erythematous oedema of both legs, without fever. After the second course, we observed the recurrence of the lesions consisting of erythemato-violaceous plaques on both legs, with severe bilateral indurated and painful oedema, associated with major functional disability. A diagnosis of bilateral erysipelas was made, and antibiotic treatment with cloxacillin was given. In both cases, pemetrexed was discontinued and the local outcome was very slowly favourable, with persistence of scleroderma. DISCUSSION: This cutaneous adverse effect is unrecognized, resulting in delayed diagnosis. It is often initially confused with bilateral erysipelas, despite absence of fever. According to some studies, the severity of the cutaneous toxicity may be connected with patients' folate status. Thus folate and vitamin B12 supplementation combined with dexamethasone could decrease the incidence of this side effect. There was no recurrence and no worsening with taxanes, chemotherapy agents known to induce scleroderma. We feel that this cutaneous toxicity must be recognised on account of its potential severity.

[Melanomatous meningitis. Apropos of 3 cases]. / La méningite mélanomateuse. A propos de trois observations.

UNLABELLED: The meninges are frequently involved during the dissemination of malignant melanoma. This "meningeal melanoma" ranks fairly high on the list of metastatic meningites, side by side with meningeal carcinomatosis proper (i.e. related to a malignant epithelial tumour). Meningeal melanoma may be associated with a cerebral metastasis or isolated, as in the three cases reported here. Although its prognosis is sombre, its diagnosis is important since the possibilities of treatment are limited but exist. CASE-REPORTS: Case 1. This was a 68-year old woman who had initially presented with malignant melanoma in the maxillary region (SSM level IV, thickness 2.9 mm). Two years after the primary tumor was excised, secondary lesions developed in the lymph nodes and bones. A few weeks later, the patient fell into mental confusion progressing towards delusion of persecution. Neurological examination and CT scans were normal, but numerous melanoma cells were found in the CSF. This woman died one month after the first neurological signs had appeared. Case 2. This 63-year old man presented with bilateral axillary adenopathy and inflammatory thoracic plaques which at histology had proved to be metastases from a malignant melanoma of the shoulder surgically treated 10 years previously. After 14 months of almost complete remission under multiple chemotherapy (CPDD, ACTD, VDS), headaches and lumbosacral pain developed. Standard radiography and CT of the spine gave normal results, and it was only at the third lumbar puncture that the CSF was found to contain malignant cells. The patient died 2 months after the first neurological manifestations. Case 3. A 42-year old woman developed headaches and dysesthaesia in the arms and head. This was followed by oppositional semi-mutism. All exploratory examinations were normal, except for that of the CSF which showed 18 cells/mm3, 50 p. 100 of which were melanoma cells. The patient was transferred to the Dermatology department where he underwent excision of a left scapular melanoma difficult to classify (malignant blue naevus?). Combined treatment with Fotemustine* and DTIC produced an incomplete but relatively prolonged response. Death occurred after 8 months. DISCUSSION: A. Meningeal melanoma accounts for about 10 p. 100 of all metastatic meningites. The most frequent primary tumours in meningeal carcinomas are breast cancer and lung cancer. Malignant melanoma ranks third or fourth, but when the relative frequency of each of these three malignant diseases is taken into account, it appears that the risk of malignant melanoma is higher than that of any other solid tumour. B. In 410 cases extracted from the literature, the meninges were involved in 30 p. 100 of malignant metastatic melanomas found at autopsy. There is no publication that makes it possible to evaluate the relative frequency of melanomas affecting only the meninges or coexisting with cerebral metastases. This also applies to meningeal melanoma associated with non-neuro