Cancer treatment reports最新文献

Following reports that specific estrogen receptors could be detected in samples of hepatocellular carcinoma tissue, a prospective randomized controlled trial was undertaken in 59 patients, half of whom received doxorubicin (60 mg/m2 at 3-week intervals) and half doxorubicin and tamoxifen (10 mg twice per day). Response occurred in three (11%) of those patients receiving doxorubicin alone and in four (16%) of those given both drugs. This difference was not statistically significant nor was the difference in survival when compared by life-table analysis. One patient treated with both drugs achieved complete remission for 30 months which was maintained (on tamoxifen alone) for 18 months before death from a non-tumor-related condition. Tamoxifen may have a role in maintenance of doxorubicin-induced remissions.

4-Ipomeanol (ipomeanol) is being developed as a potential antitumor agent to treat lung cancer. Ipomeanol produced a dose-related toxicity in CD2F1 mice, Fischer 344 rats, and beagle dogs. The LD50 in mice after a single iv dose of ipomeanol was 35 mg/kg in males and 26 mg/kg in females. Minimal cumulative toxicity occurred in mice after seven doses; LD50 was 30 mg/kg/day in males and 21 mg/kg/day in females. In rats, iv doses greater than or equal to 15 mg/kg were lethal. Labored respiration, terminal bronchiolar epithelial necrosis, interstitial inflammation, and alveolar edema were present in rats dosed with ipomeanol at greater than or equal to 9 mg/kg. In addition to pulmonary lesions, splenic and thymic lymphocyte depletion and/or necrosis was present. Ipomeanol had little cumulative toxicity in rats given seven daily doses. In dogs, iv doses greater than 12 mg/kg were lethal. Dogs treated with lethal doses of ipomeanol showed rapid, shallow respiration and pulmonary edema prior to death; diffuse pulmonary congestion or hemorrhage and diffuse renal congestion were present at necropsy. Pulmonary microscopic changes caused by nonlethal doses of ipomeanol included subacute interstitial inflammation and necrosis of respiratory bronchiolar and alveolar duct epithelium. In contrast to rodents, seven daily doses of ipomeanol were cumulatively toxic in dogs. The nonlethal pulmonary effects of ipomeanol were reversible in all three species. Tolerance to lethal doses of ipomeanol occurred in animals of all three species pretreated with multiple nontoxic doses of the drug. The LD50 of ipomeanol in male and female mice increased 2.4- and 4.5-fold, respectively, in tolerant mice. In rats and dogs, previously lethal doses of 48 and 24 mg/kg were nonlethal after tolerance was induced by pretreatment with seven daily doses of ipomeanol.

The distribution of the novel alkylating agent clomesone [2-chloroethyl (methylsulfonyl)-methane sulfonate] has been studied in mice after iv administration of 35 mg/kg. In plasma, [14C]clomesone was eliminated in an apparent single phase with a half-life of 11 minutes. The elimination of total radioactivity occurred with an initial half-life of 51 minutes, and then in prolonged phase of undetermined length. At least two organic soluble metabolites were detectable in plasma. Highest tissue concentrations of radioactivity were in liver, kidney, and small intestines where, at most times of analysis, the levels were two to three times higher than those in plasma. The rate of elimination of radiolabel from spleen, lungs, brain, and muscle, which contained about equal concentrations of radioactivity at most times after dosing, paralleled the rate of loss from plasma. A major proportion of the radioactivity in tissues was bound to trichloracetic acid-precipitable macromolecules. Within 24 hours, 77.6% of the dose was recovered in urine. High-pressure liquid chromatographic analyses of 8-hour urine collections demonstrated that less than 2% of the dose was excreted unchanged. These results demonstrate that clomesone is rapidly eliminated from plasma and that it and/or its products become extensively bound to tissue components.

Lonidamine, a substituted indazole carboxylic acid that inhibits cellular respiration, was given in an escalating oral schedule to 20 evaluable patients with measurable extensive small cell carcinoma of the lung. Two partial responses occurred. Reversible acceptable toxicity included myalgia, nausea, hyperesthesia, photophobia, somnolence, and testicular pain. The drug was not myelosuppressive. Lonidamine has modest activity in small cell lung cancer and further studies are warranted.