Phase II trial of edatrexate in patients with advanced pancreatic adenocarcinoma.

BACKGROUND: The methotrexate analogue 10-ethyl-10-deazaaminopterin (10-EdAM, or edatrexate) has shown antitumor activity in preclinical testing and clinical studies of patients with breast, lung and head and neck carcinomas. A phase II study was conducted in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Forty patients were enrolled on the clinical trial. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly for 5 weeks. The treatment course was repeated every 6 weeks. RESULTS: Two partial responses were observed. Both of these patients had partial responses which lasted 2 and 3.5 months. The median survival for all patients was 3.5 months. Serious (grade 3 or 4) toxic effects were primarily mucosal, hematologic, and dermatologic. Two patients experienced severe pulmonary toxic reactions. CONCLUSION: At the dose and schedule used, edatrexate was poorly tolerated and did not demonstrate significant antitumor activity.

In adult acute nonlymphoblastic leukaemia extended maintenance chemotherapy has no benefit.

Fifty-two consecutive and previously untreated adults with nonlymphoblastic leukaemia underwent remission induction chemotherapy with a combination of the epipodophyllotoxin VP16-213, cytosine arabinoside, and doxorubicin (Adriamycin). Complete remission was achieved in 23 of the 52 patients (44%) by means of a single course of therapy in 20 individuals, two courses in two, and three courses in one; median duration of complete remission was 48 weeks. Failure to achieve remission status was due to primary drug resistance in 13 patients (25%), and adequate trial of therapy was not possible in 16 patients (31%) owing to their late referral and accounts for the low remission rate. Individuals achieving complete remission were randomly assigned to receive either 6 (n = 8) or 15 months (n = 13) of maintenance therapy; respective median survival was 95 and 78 weeks (P greater than 0.10). These data confirm previously reported results for complete remission induction with this three-drug combination and fail to show any difference between short (6 months) and long (15 months) maintenance chemotherapy.

Lymphocytic lymphoma, hypereosinophilia and endomyocardial fibrosis.

A 32-year-old man presented with left hypochondrial pain and myalgia. On examination he was found to have widespread lymphadenopathy and splenomegaly, and lymph node biopsy revealed diffuse lymphocytic lymphoma of the small cleaved cell type. There was hypereosinophilia (20 x 10(9)/1). The patient was initially treated with chlorambucil and prednisone, which controlled the lymphoma for 9 months but did not affect the eosinophilia. He then developed thrombocytopenia with further lymph node enlargement which was managed with a combination of bleomycin, vincristine and prednisone; this again controlled both spleen and lymph node size without affecting the eosinophilia. Six months after presentation the patient developed refractory cardiorespiratory failure due to endomyocardial fibrosis and fibrosing alveolitis. The cardiac failure was thought to be related to the hypereosinophilia resulting from the lymphoma, while the respiratory insufficiency was attributed to the bleomycin. This case illustrates the rare association between lymphocytic lymphoma and eosinophilia and shows that cardiac damage can be associated with these cells.

Bone marrow transplantation followed by normal pregnancy.

A full-term normal male child was delivered using forceps fifteen months after successful allogeneic bone marrow transplantation in a woman who presented with severe acute aplastic anemia. The uneventful course of this pregnancy demonstrates that the high-dose cylcophosphamide administration used to prepare the patient for the procedure need not irreversibly suppress ovarian or endocrine function. This observation has relevance for the increasing numbers of young patients with aplastic anemia or acute leukemia undergoing bone marrow transplantation.

The role of continuous-flow blood fraction separators in clinical practice.

Continuous-flow blood fraction separators facilitate the efficient exchange of large volumes of plasma or red cells and therefore have clinical application in the rapid correction of abnormalities located predominantly in either of these compartments. Plasmapheresis has been successfully used in managing 2 patients with previously refractory myasthenia gravis, in reducing the antibody titre in a rhesus-sensitized woman, and in diminishing anti-A titre in a patient requiring bone marrow transplantation from an ABO-incompatible but HLA- and MLC-identical sibling. Continuous-flow red cell exchange effectively reduced the haemoglobin S concentration in an individual with sickle cell disease prior to general anaesthesia and abdominal surgery. Complications were not encountered although the procedures were carried out repetitively over prolonged periods of time. All 5 patients tolerated their exchanges without discomfort. As with any new and expensive technique, caution should attend the introduction of continuous-flow plasma or red cell exchange into clinical medicine. Careful evaluation of the safety and the benefits is needed to establish perspective and to distinguish between established and developmental indications.

The University of Cape Town leukaemia centre: the first 5 years.

In the last 5 years there has been an increasing commitment to cell support regimens and bone marrow transplantation in leukaemia and the clinical service has developed in parallel with laboratory-based research programmes. In the acute leukaemias there has been a major attempt to improve diagnostic accuracy and to classify the tumours functionally, while the clinical approach is currently comparing bone marrow transplantation during the first complete remission with early or late cytotoxic intensification programmes. As regards cell support, allogeneic granulocytes and platelets are being provided for patients in both the leukaemia and the transplantation programmes. In addition, new techniques are being developed for increasing the efficiency of cell collection and characterizing their in vitro function. Bone marrow transplantation is the preferred form of treatment for patients with severe acute aplastic anaemia. Laboratory research is directed at defining graft-versus-host disease and attempting to eliminate this phenomenon with immunological adjuvants.

Continuous flow plasma exchange in the treatment of homozygous familial hypercholesterolemia.

We report the clinical and laboratory effects of continuous-flow plasma exchange in two patients suffering from homozygous familial hypercholesterolemia. In one (Case 1) plasmapheresis was performed at fortnightly intervals over a period of 18 months; in the other (Case 2) the necessity for surgical relief of an associated supravalvular aortic stenosis resulted in premature termination of the trial. The plasma cholesterol levels in both patients fell by 35 per cent from the mean before study in the course of treatment. In Case 1 this was associated with marked regression of the patient's xanthomas, disappearance of the S-T segment depression seen on effort electrocardiograms obtained prior to the introduction of plasmapheresis, possible widening of the stenosis present at the origin of the left anterior descending coronary artery, and a marked increase in exercise tolerance and diminished frequency of anginal attacks. Cessation of cholestyramine and clofibrate administration during this study did not in any way reverse the reduction of plasma cholesterol achieved by means of plasmapheresis combined with drug therapy. We conclude that plasmapheresis has a role to play in the management of patients with homozygous familial hypercholesterolemia.