Cancer chemotherapy reports最新文献

The toxic effects of cytembena in beagle dogs and rhesus monkeys were investigated with the drug given as single or daily iv injections in doses ranging from 12.5 to 200 mg/kg/day to dogs and 6.25 to 50 mg/kg/day to monkeys. Renal tubular damage was a major drug- and dose-related finding in both species and was clinically indicated by an accompanying uremia, elevated serum creatinine, and proteinuria. In the kidney, the primary lesion was cellular necrosis and desquamation of the distal tubular epithelium in animals given the lowest toxic doses. More severe but similar histologic changes produced by this drug were further characterized by single dose studies in mice which showed renal mitochondrial swelling and disruption plus generalized cell swelling as progressive, subcellular developments which were well established 24 hours after treatment. Cellular regeneration in the renal tubular epithelium was found in dogs and monkeys retained 6 weeks for observation after treatment, although functional recovery was inconsistent. A toxic effect to lymphoid tissue was an additional finding which is described.

Transplantable adenocarcinomas of the colon in mice have been developed from primary tumors induced by 1,2-dimethylhydrazine. Two such transplant lines, MAC-13 and MAC-15, have been used to assess the possible value of this type of tumor in chemotherapy screening. A protocol has been established and 11 standard drugs were tested against the two lines. Both tumors show sensitivity which is remarkably similar to that of human large bowel cancer, and MAC-13 would have correctly predicted the activity in man for ten of the 11 drugs. Quantitatively, CCNU, methyl-CCNU, and cyclophamide were the most effective drugs. A comparison of the predictive efficiencies of L1210 leukemia, B16 melanoma, and these new tumors as screening systems for colorectal cancer is made and discussed.

An initial clinical trial of daily and weekly X 6 ihtravenous infusions of thalicarpine, a plant alkaloid of novel structure, was carried out in 36 patients. Twenty-eight patients received 33 courses of single-dose administration at doses of 200-1900 mg/m2. At the maximum tolerable dose of 1400 mg/m2, toxic effects included arm pain (nine or ten), central nervous system depression (seven of ten), nausea and vomiting (two of ten), hypotension (two of ten), hypertension (two of ten), arrhythmia (premature ventricular contractions) (one of ten), and electrocardiographic changes (mainly T-wave flattening) (five of ten). At the maximum tolerable dose for weekly administration, 1100 mg/m2/week X 6, arm pain was seen in seven of eight, central nervous system depression in three of eight, hypotension in one of eight, and electrocardiographic changes in three of eight. The recommended dose for phase II trials is 1100 mg/m2/week by a 2-hour intravenous infusion.

Amygdalin MF was evaluated alone and in combination with an activating agent, beta-glucosidase, against three transplantable rodent tumors; Ridgway osteogenic sarcoma, Lewis lung carcinoma, and P388 leukemia. In dose-response studies up to the LD20 in normal mice, amygdalin MF alone did not demonstrate significant antitumor activity against any of these three tumor systems. Similarly, at doses not exceeding the LD10 in normal mice, amygdalin MF plus beta-glucosidase did not demonstrate antitumour activity against any of these three tumor systems. Potentiation of the lethal toxicity of amygdalin MF by beta-glucosidase was observed in all studies where the two agents were given in simultaneous combination.