Cancer chemotherapy reports最新文献

Twenty-three patients with stage III germinal neoplasia of the testis were treated with a variation of our original vinblastine-bleomycin program. This modification consisted of 0.4 mg/kg of vinblastine given in two fractions on Days 1 and 2 followed by continuous intravenous administration of 30 units of bleomycin in 1000 cc of 5% glucose and distilled water over a 24-hour period for 5 successive days beginning on Day 2. Therapy was repeated every 28-35 days as toxicity permitted. There were 17 responses, nine of which were complete (39%). Eight of the complete responses were in patients with massive disease in whom a low complete response rate was expected. Toxic effects consisted of severe leukopenia in 90% thrombopenia in 50%, and unexplained transient hyperbilirubinemia in about 30% of the patients. Bleomycin pneumonitis occurred in one patient and resulted in death. Hypertension was a new and unexpected side reaction experienced by four patients. Further trials are indicated since the complete response rate in patients with advanced massive disease appears to be improved.

The effect of in vivo treatment of C57BL mice with BCNU and/or levamisole on the in vitro DNA synthetic capacity of their spleen cells was studied as a measure of cell-mediated immune function. BCNU treatment was suppressive to spleen cell DNA synthesis; conversely, treatment with levamisole was stimulatory. Levamisole treatment 5-8 days after BCNU treatment resulted in significant recovery of DNA synthetic capacity. Multiple doses of levamisole were not more effective than single doses. Allogeneic stimulation of BCNU-suppressed lymphocytes was not consistently increased by levamisole treatment.

Several group IIIa metal salts, eg, aluminum nitrate, gallium nitrate, indium nitrate, and thallium chloride, have been evaluated for in vivo toxicity in mice and rats, for cytotoxicity in tumor cells in vitro, and for activity against a broad spectrum of experimental rodent tumors. The position of these agents in the periodical table roughly parallels their toxicity, the LD50s decreasing with increasing atomic weights. This parallel also exists with regard to in vitro cytotoxicity to Walker 256 carcinosarcoma cells. Although all of the metal salts had activity against the ascites Walker 256 carcinosarcoma, they were ineffective in ascites leukemias, plasma cell tumors, or Ehrlich carcinoma. Gallium nitrate was particularly active against solid tumors transplanted subcutaneously, suppressing the growth of six of eight tumors more than 90%. Because of its demonstrated antitumor activity in rodents and its uptake and concentration by various animal and human tumors, gallium nitrate has potential usefulness in the treatment of solid tumors in man and has been entered into a phase I study at the National Cancer Institute.

Rosenberg and VanCamp first reported the bacteriostatic and antitumor properties of certain platinum coordination compounds. This pioneering work has led to the synthesis and testing of a large number of related platinum products and the clinical use of cis-dichlorodiammineplatinum (II). This drug has proven very efficacious against a wide variety of mouse tumors when employed as the sole chemotherapeutic agent and has also been combined successfully with other antitumor agents, such as cyclophosphamide and cytosine arabinsoide. Unfortunately, cis-dichlorodiammineplatinum (II) has a low therapeutic index with renal toxicity being the principal limitation of its use. This has prompted the synthesis and testing of many related platinum compounds, of which cis-dichlorobiscyclopentylamine-platinum (II) and the "platinum blues" appear most promising. Experience in the synthesis, purification, and testing of such products will be discussed together with identification of outstanding unsolved problems in this area.

The nobel metal "cage" complex, rhodium(II) acetate, was found to inhibit the deamination of the fraudulent nucleoside, arabinosylcytosine. Potent inhibition of a purified cytidine deaminase from mouse kidney was observed when either cytidine or arabinosylcytosine was used as substrate.