A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1 x 10(5) units/m2. The dose was escalated up to 16 x 10(5) units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16 x 10(5) units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12 x 10(5) units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5 x 10(5) units/m2.

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The occurrence of adrenal myelolipomas is reported in an untreated patient with congenital adrenal 21-hydroxylase deficiency. Laparotomy demonstrated the presence of two lesions, a large tumor which arose from an ectopic adrenal cortex and a smaller tumor in the left adrenal gland. Six cases of adrenal myelolipomas and congenital adrenal hyperplasia have been reported in the literature. All patients were associated with excessive ACTH secretion for a long period of time. The relative frequency of this association, coupled with the observation by Selye and Stone (Am J Pathol 26:211, 1950) that anterior pituitary extracts cause myelolipomatous changes in rats, may indicate a possible role for ACTH in the development of myelolipomas. (Internal Medicine 31: 803-806, 1992)

Background. MST‐16, a new orally administered bis(2,6‐dioxopiperazine) analogue and an inhibitor of topoisomerase II, was given to 24 patients with adult T‐cell leukemia‐lymphoma (ATLL) in a Phase I‐II multiinstitutional cooperative study. Methods. MST‐16 was administered orally daily for 7 days, with courses repeated at intervals of 2–3 weeks in 24 patients. Results. Two complete remissions (CR) and eight partial remissions (PR) were obtained in 23 evaluable patients who received 1200–2800 mg/day of MST‐16. Among 13 acute‐type ATLL, one CR and five PR were obtained. Among eight lymphoma‐type ATLL, two PR were detected. Among two chronic‐type ATLL, one CR and one PR occurred. Remissions were obtained at 7–232 days (median, 23 days) and lasted 43–374 days (median, 68 days). The major toxic effects were leukopenia (68%), anemia (52%), thrombocytopenia (35%), and gastrointestinal disorders (22%). Conclusions. MST‐16 was shown to be effective in ATLL, which has no standard therapy. This drug deserves further clinical trials because it shows little cross resistance to currently available antitumor drugs.