Treosulfan in the treatment of metastatic renal cell carcinoma.

BACKGROUND: Treosulfan is a bifunctional alkylating cytostatic agent that has mainly been used in the therapy of advanced ovarian cancer. Lately, a growth inhibiting effect could be detected in human renal cell carcinoma-cell lines as well. In vitro, Treosulfan showed an even higher growth inhibition than Vinblastine. MATERIALS AND METHODS: We performed a small clinical phase II study using Treosulfan as a monotherapy in the treatment of metastatic renal cell carcinoma. Treosulfan was given to 15 patients with bidimensionally measurable metastases. RESULTS: 10 patients were evaluable. Side effects were negligeable. A complete or even partial remission was not seen. 4 patients showed no change, whereas 6 were progressive. The average time to progress was short (4 months, range 1 to 12 months). CONCLUSIONS: Since Treosulfan did not lead to a measurable tumor remission in the given dose regimen, it does not seem to be suitable for the therapy of metastatic renal cell carcinoma.

Unchanged 5'-deiodinating activity during the induction of a nonthyroidal illness.

We investigated the formation of a "nonthyroidal illness" (NTI) in pigs undergoing ventricular fibrillation (VF) and resuscitation. Seven minutes after VF twenty-one pigs received either Epinephrine (E: 45 micrograms/kg B.W.; n = 7), Norepinephrine (NE: 45 micrograms/kg B.W.; n = 7), or Vasopressin (VP: 0.8 U/kg B.W.; n = 7). We determined the serum concentrations (sc) of total T4 (TT4), FT4, total T3 (TT3) and rT3 120 min before, during (t0), and 5, 15, 60 and 120 min after VF. At the end of the observation period we figured out the in-vitro T3-generation (kM, Vmax), the in-vitro rT3-generation, the in-vitro rT3-decomposition (kM, Vmax) and the content of cytosolic sulfhydryls (total sulfhydryls, non-protein bound sulfhydryls) in liver and kidney specimen. Animals not undergoing VF served as controls (C) for parameters measured in the intracellular compartment. TT4- and TT3-sc decreased to 3.3 +/- 0.6 micrograms/dl (p < 0.05, vs. t0) and 15.2 +/- 4.1 ng/dl (p < 0.05, vs t0), resp. FT4-sc remained stable for five minutes (2.63 +/- 0.41 ng/dl) before declining to 1.8 +/- 0.39 ng/dl (p < 0.05, vs. t0). The rT3-sc raised finally to 46.9 +/- 7.3 ng/dl (p < 0.05, vs t0). Iodothyronine sc did not exhibit differences between E-, NE- and VP-treatment. Neither in-vitro T3-generation, nor in-vitro rT3-generation, nor in-vitro rT3-decomposition nor intracellular sulfhydryl content were affected by the events of VF and resuscitation as compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)