Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases

One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.     

Sickle cell anemia patients have low erythropoietin levels for their degree of anemia

We have studied serum immunoreactive erythropoietin (SIE) levels in 28 patients with sickle cell anemia (SCA) without renal insufficiency and in 17 patients with nonhemoglobinopathy anemias of comparable severity using a sensitive radioimmunoassay procedure. An exponential relationship between SIE level and degree of anemia was noted in all patients. However, in nonhemoglobinopathy anemia, a sharp rise in the SIE level occurred as hemoglobin (Hb) levels fell below about 12 g/dL, whereas in sickle cell patients the increase was not marked until hemoglobin fell to about 9 g/dL. The response was more blunted in older SCA patients than in younger ones. A linear regression model relating SIE level to Hb level, presence/absence of SCA, and age explained 63% of the variation in SIE. We conclude that the serum erythropoietin levels in SCA increased at a lower hemoglobin concentration and are of a lower magnitude than that of the other anemias.     

Management of oral Kaposi's sarcoma and a proposal for clinical staging

Kaposi's sarcoma (KS) is the most common neoplastic disease in patients with disease due to human immunodeficiency virus (HIV), and oral KS (OKS) is the commonest oral neoplasia. OKS has been managed by local excision, intralesional chemotherapy regional radiotherapy, and systemic chemotherapy. Comparison between studies is difficult as the severity of oral involvement is not well defined in most studies. This paper reviews the approach to the management of OKS and also presents a proposal for the clinical staging of OKS. Clinical staging of OKS will facilitate comparisons of outcomes of treatment of OKS and improve our understanding of the natural history of the neoplasia, which has varied presentation and rates of progression.     

Effect of shunt surgery on spleen size, portal pressure and oesophageal varices in patients with non-cirrhotic portal hypertension

Shunt surgery is considered to be the treatment of choice in patients with non-cirrhotic portal hypertension. There is little data on the effect of side-to-side lieno-renal (SSLR) shunt on oesophageal variceal size, splenic size and splenic pulp pressure (SPP) in patients with non-cirrhotic portal hypertension. We evaluated pre- and postoperatively endoscopic grading of varices, splenic size and SPP for predicting shunt patency in 86 patients with non-cirrhotic portal hypertension: 56 with extrahepatic portal venous obstruction (EHPVO) and 30 with non-cirrhotic portal fibrosis (NCPF). The EHPVO patients with patent shunts (n= 47) showed significant reduction in SPP (pre-operative 43.56±7.9 vs postoperative 29.96±7.7 cm of saline), splenic size (6.5±2.8 vs 4.00±2.6 cm below costal margin) and varices grades (2.96±0.5 vs 0.92±0.8). Patients with blocked shunt (n= 9) did not show significant reduction in SPP and varices grades. However, there was reduction in spleen size (8.6±3.0 vs 6.3±4.3). In the NCPF group, 28 had patent shunts and showed significant reduction in SPP (46.3±13.5 vs 33.8±7.6 cm of saline), splenic size (9.1±3.3 vs 6.8±4.6 cm below costal margin) and varices grades (2.8±0.7 vs 1.05±0.96). As only two patients with NCPF had blocked shunts, no statistical comparison between patients with patent and patients with blocked shunts could be done. In conclusion, following SSLR, there is a significant reduction in SPP and varices grades in patients with patent shunts. Endoscopic grading of varices can be used to predict shunt patency. However, spleen size is not a good criteria for predicting shunt patency.     

小叶买麻藤中买麻藤甲素的结构研究

从小叶买麻藤[Gnetum parvifolium(Warb.)C.Y.Cheng]茎的乙酸乙酯部分得到五个成分,经理化常数测定、光谱(UV,IR,MS,~1HNMR,~(13)CNMR和2D-NMR)分析和衍生物制备,确定买麻藤甲素为一个新的2-苯基苯并呋喃类化合物,结构为2-(3′,5′-二羟基-4′-甲氧基苯基)_-3-甲氧基5-羟基苯并呋喃。另外三个鉴定为异丹叶大黄素、白黎芦醇和β-谷甾醇.还有一个化合物正在鉴定中。     

Study of high doses of carboplatin as a first choice in the therapy of advanced ovarian cancers]

Thirty female patients with ovarian cancer of poor prognosis were included in a chemotherapy trial using high dose IV carboplatin--800 mg/m2 every 5 weeks. The subjects had three to six cycles prior to second laparotomy. Twenty-eight patients were assessable. There was no neurological, auditory or renal toxicity. Limiting toxicity was haematological, the mean neutrophil count was less than 650 mm3 and the mean platelet count less than 30,000/mm3. No death occurred from toxicity. The clinical response rate was 67%, and the surgical response rate 53.5%, with 15% complete histological responses. Survival at 18 months is 36%. A trial concerning 36 patients treated with an association of carboplatin at the same dose combined with cyclophosphamide has just been completed and the results are being analyzed.     

Combination chemotherapy of dacarbazine and fotemustine in disseminated malignant melanoma

Summary A total of 70 patients presenting with a disseminated malignant melanoma were entered into a multicentric study of combination chemotherapy using dacarbazine and fotemustine. In all, 63 patients were evaluable, 31.8% of whom had previously received cytotoxic chemotherapy. The protocol consisted of induction treatment with a weekly infusion of 100 mg/m² fotemustine on days 1 and 8 and a daily infusion of 250 mg/m² dacarbazine on days 15/18 followed by a 4- to 5-week rest period. Responding and stabilized patients were given maintenance treatment comprising fotemustine (100 mg/m², day 1) and dacarbazine (250 mg/m², days 2/5) every 3 weeks. The response rate was 33.3% (9 complete responses (CRs) and 12 partial responses (PRs)) and was outstanding among pretreated patients (34.9%). Responses were also documented in cerebral (28.6%), visceral (23.1%) and nonvisceral (43.3%) metastatic sites. Toxicity was mainly hematologic (22.2%, grade III/IV leukopenia; 20.3%, grade III/IV thrombocytopenia) and was acceptable. These results are encouraging in terms of the antitumor activity against nonvisceral metastases (43.3%) and the percentage of CRs obtained (23.3%), and they confirm the activity of fotemustine in cerebral metastatic sites.Other investigators involved in this trial included B. AUDHUY, CHR Louis Pasteur, Colmar; A. BERNADOU, Hôtel Dieu, Paris; J. J. BONERANDI, Hôpital Ste Marguerite; F. DANIEL, Hôpital St Joseph. Paris; P. FARGEOT, Centre Georges François Leelerc. Dijon; Pr KALIS, Hôpital Sébastopol, Reims; B. LABEILLE, Hôpital Sud, Amiens; P. LAURET, Centre Henri Becquerel, Rouen; P. LTTOUX, Hôtel Dieu, Nantes; G. LORETTE, Hôpital Trousseau, Chambray les Tours: R. METZ, Centre Alexis Vautrin, Vandoeuvre les Nancy; M. MOUSSEAU, CHR de la Tronche, Grenoble; J. L. VERRET, CHR, Angers, France