Feasibility study of high-dose carboplatin and etoposide in the salvage treatment of testicular cancer.

Eleven patients with testicular cancer, either relapsing after or refractory to cisplatin-based chemotherapy, underwent salvage chemotherapy with high-dose carboplatin (800 mg/m2 on day 1) and high-dose etoposide (500 mg/m2 on days 1, 3 and 5). A total of 21 courses were administered. The major toxicity consisted of profound myelosuppression. There were two toxic deaths, both caused by infection during neutropenia. Bone marrow recovery was usually complete around day 26 (range 19-129). Other toxicities included mild mucositis, nausea and vomiting, and alopecia. No significant neurotoxicity or hearing loss were observed and only one patient had a moderate decrease in renal function. Nine of ten evaluable patients responded, with one complete remission, 6 partial remissions with normalization of tumor markers, and two partial remissions with over one log decrease of tumor markers. The duration of these remissions was not evaluable, since only three evaluable and responding patients did not receive additional therapy after HD-CE. All three relapsed after discontinuing chemotherapy. HD-CE has activity in relapsing or refractory testicular cancer and can be administered without bone marrow support. The regimen may thus be suitable to be used as a remission induction regimen prior to consolidation with intensive chemotherapy and autologous bone marrow transplantation.     

The treatment of hairy-cell leukaemia with 2''-deoxycoformycin

Eight patients with hairy-cell leukaemia (HCL) complicated by pancytopenia were treated with low dose regimens of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (DCF). All patients had significant haematological and clinical improvement. One patient who had been splenectomized and five patients with mild to moderate splenomegaly achieved normal blood counts within 2 months, which have been maintained for up to 18 months. Complete remissions occurred in two patients and four patients had 50-95% marrow clearance of hairy cells. The initial DCF treatments produced a 1-3 g/dl fall in the haemoglobin levels and one patient had a temporary reduction in granulocyte and platelet counts. Five patients had nausea/vomiting, and/or lethargy following DCF, but there was no correlation between the plasma levels of deoxyadenosine and adenosine and the incidence or severity of these side effects. An increased incidence of infection and drug hypersensitivity may reflect the effects of DCF on the immune system. Low dose DCF is a highly effective agent in HCL.     

Platelet dense granule membranes contain both granulophysin and P-selectin (GMP-140).

We recently reported the characterization of a platelet granule membrane protein of molecular weight (mol wt) 40,000 called granulophysin (Gerrard et al: Blood 77:101, 1991), identified by a monoclonal antibody (MoAb D545) raised to purified dense granule membranes. Using immunoelectron-microscopic techniques on frozen thin sections, this protein was localized in resting and thrombin-stimulated platelets. In resting platelets, labeled with antigranulophysin antibodies and immunogold probes, label was localized to the membranes of one or two clear granules per platelet thin section. D545 also labeled dense granules in permeabilized whole platelets and isolated dense granule preparations examined by whole-mount techniques. Expression of granulophysin on the platelet surface paralleled dense granule secretion as measured by 14C-serotonin release under conditions in which lysosomal granule release, as measured by beta-glucuronidase secretion, was less than 5%. After thrombin stimulation, both the surface-connected canalicular system and the plasma membrane were labeled, demonstrating redistribution of granulophysin associated with degranulation. Double labeling experiments with D545 and antibodies to the alpha-granule membrane protein, P-selectin, demonstrated labeling of both P-selectin and granulophysin on dense granule membranes. Distribution of both proteins on the plasma membrane after platelet stimulation was similar. The results demonstrate that granulophysin is localized to the dense granules of platelets and is redistributed to the plasma membrane after platelet activation.