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Biomedical subjects

B Drewinko

Publications and source records attributed to B Drewinko.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Review of the current clinical status of platinum coordination complexes in cancer chemotherapy.

During the past 3 years, eight hospitals and one cooperative study group have reported their initial clinical results with cis-dichlorodiammineplatinum (II). The most popular clinical schedule was 15-25 mg/m2/day for 5 days repeated every 3-4 weeks. Almost all patients had extremely advanced disease. Of 323 patients in whom response could be evaluated, there were 12 complete responses, 25 partial responses (greater than 50% decrease in tumor size), and 23 improvements (greater than 50% decrease in tumor size) for a 19% overall response rate. The tumor most sensitive to cis-dichlorodiammineplatinum (II) was testicular carcinoma in which seven complete responses, three partial responses, and three improvements were observed in 16 patients treated at Roswell Park Memorial Institute. Other sensitive tumors were lymphoma (63% response and improvements), squamous cell carcinoma of the head and neck (41% response and imporvements), and ovarian carcinoma (40% response and improvements). Complete responses were also seen in one patient with thyroid carcinoma and two with bladder carcinoma, while partial remissions were recorded in two patients with breast carcinoma and one patient each with acute myelogenous leukemia, endometrial carcinoma, renal carcinoma, malignant thymoma, neuroblastoma, adenocarcinoma of the lung, and an undifferentiated tumor of unknown origin. Five major types of toxicity were encountered: gastrointestinal, hematopoietic, immunosuppressive, otologic, and renal, with the last two generally the most serious. Serial audiometry testing can generally warn of the otologic toxicity and thus prevent permanent acoustic damage. Renal toxicity, which is similar to that seen with heavy-metal poisoning, appears to be dose related, cumulative, and only partly reversible, thus, severely limiting the repeated administration of cis-dichlorodiammineplatinum (II). Recent laboratory studies suggest that combination chemotherapy with this drug may be rewarding. Studies of this nature should be pursued along with attempts to find more effective less toxic platinum compounds.

Antineoplastic Agents↗
PubMedDate not supplied

Action of Cis-dichlorodiammineplatinum(II) (NSC-119875) at ehe cellular level.

Asynchronous human lymphoma cells treated for 1 hour with increasing concentrations of cis-dichlorodiammineplatinum(II) revealed a marked decrease in survival as estimated by the colony-forming technique. When the treatmentwas extended for 8 hours at a concentration of 5micrograms/ml, a killing effect (greater than 3 log decades) was observed which was similar to that obtained when 50micrograms/ml is incubated with the cells for 1 hour. This finding suggests that better antitumor effects with fewer toxic effects may be obtained clinically by prolonged infusion of low doses of cis-dichlorodiammineplatinum (II). Synchronized lymphoma cells showed no significant degree of cell-cycle-stage sensitivity to cis-dichlorodiammineplatinum (II). The drug kills cells with similar efficiency in all stages of the cell cycle. No killing effect was elicited after incubation of the cells with spironolactone, a compound said to protect the kidneys from the toxic effects of heavy metals. However, simultaneous incubation of spironolactone and cis-dichlorodiammineplatinum (II) did not prevent the lethal action of the second drug. If spironolactone is proven to be an inhibitor of cis-dichlorodiammineplatinum (II) nephrotoxicity, it will become a valuable addition to the treatment of human neoplasia with this platinum compound. Lymphoma cells given a "priming" dose of 10 micrograms/ml of cis-dichlorodiammineplatinum (II) failed to repair the induced damage. A second exposure to 10 micrograms/ml of the drug at various subsequent intervals elicited greater killing effect than that produced by 20 micrograms/ml given at one time. A clear synergistic effect was noted when cis-dichlorodiammineplatinum (II) was given simultaneously with camptothecin or BCNU. The molecular mechanism by which this effect is accomplished is not presently apparent.

Camptothecin↗