Fotemustine is a new chloroethylnitrosourea characterized by the grafting of a phosphonoalanine group onto a nitrosourea radical. Clinical studies using fotemustine have been conducted in malignant glioma, brain metastasis of non-small cell lung cancer, and disseminated malignant melanoma. In recurrent malignant glioma, fotemustine has been used as a single agent: assessed by computed tomography scan, after 8 weeks, the objective response rate was 26.3% among 38 evaluable patients. Median duration of response was 33 weeks. The main toxicity was hematological (thrombocytopenia and leucopenia). A trial with high-dose fotemustine and autologous bone marrow rescue in newly diagnosed glioma was conducted in 26 patients, and 6 showed a partial response. The median overall survival was approximately 11 months. Myelosuppression was noted in all patients except 1, and other toxicity reported was central nervous system toxicity and epigastric pain. Combined with radiotherapy in 55 patients, a 29% response rate was observed, and this combination was well tolerated and easily manageable on an outpatient basis. Finally, fotemustine has been used intraarterially, with 10 objective responses observed among 26 evaluable patients. In brain metastases of non-small cell lung cancer, fotemustine proved to be active with a response rate of 16.7%. Combined with cisplatinum, fotemustine is still under study, but preliminary results are promising. In cerebral metastases of disseminated malignant melanoma, fotemustine has been evaluated in a total of 140 patients in the various studies: median response rate is 24.3%, ranging from 8.3% to 60.0%. Fotemustine appears to be a good candidate in the treatment of primary brain tumors and metastases.

Over a period of 4 years, metastatic lesions to the gastrointestinal tract were analysed in postmortem and clinical series. Melanoma, breast and lung cancers were the most common primary lesions. The topography of parietal involvement shows that all patients evidenced tumor involvement of the submucosa, but not all of them revealed invasion of the mucosa and serosa, suggesting a hematogenous route of dissemination. Although almost all cases had widespread disease at the time of referral for diagnosis, patients who were submitted to surgery had a median survival of 8 months (range 1-48). In selected cases, surgery offers good palliation and may permit resumption of otherwise active chemotherapeutic treatments.

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This article reviews the current developments and significant trends in the treatment of hepatocarcinoma (HCC). Prevention programs should be based on large vaccination campaigns and the use of immunologic or biologic molecules to delay the onset of HCC in already cirrhotic patients. Surgery remains the therapy of choice in patients with a small and limited number of tumor nodules. To date, no preoperative treatment has been proven useful. Adjuvant treatments involving systemic chemotherapy, intra-arterial infusion, or chemoembolization failed to improve survival, whereas immune therapy, retinoids, radiolabeled isotopes, and antiangiogenic agents seem promising. Such local treatments as percutaneous ethanol injection, cryotherapy, and radiofrequency are proposed for patients with limited hepatic function and should be combined with other treatment modalities to optimize their efficacy and limit their toxicity. Regional therapy should take a selective, subsegmental approach at intervals depending on tumor response and possibly combined with other treatment modalities. Systemic therapy with cytotoxic agents remains disappointing. Hormonal therapy with tamoxifen or antiandrogens has shown no efficacy and might even be detrimental. Further progress may be expected from targeted therapy.