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.