Clinical Trials with Adriamycin in Leukemia and Solid Tumors

Adriamycin is a new antitumor antibiotic of the anthracycline group. Its chemical structure is very close to that of daunorubicin. Pharmacological studies demonstrated that adriamycin has a higher therapeutic index (1.21) than daunorubicin (0.67). Adriamycin was given intravenously to 53 patients with different types of leukemia and cancer (13 children and 40 adults). Three doses were used: 0.4 mg/kg (pretreated patients), 0.65 mg/kg (untreated adults), 0.8 mg/kg (children). Three different schedules were also employed regardless of the single dose/kg (table 1): A) Loading-dose schedule: treatment for 4 consecutive days followed by a 3 day interval: the drug was then restarted 1–2 times a week; B) Alternate day-dose schedule: treatment every other day for 4–6 doses followed by a 3 day interval; the drug was then restarted 1–2 times a week; C) Intermittent-dose schedule: two treatments for 3 consecutive days separated by two intervals of 4 days; the drug was then restarted 1–2 times a week. The chief evidence of toxicity was a triad of symptoms: stomatitis, bone marrow depression and alopecia (table 2). The oral ulcerations where the first sign of toxicity in more than 50 % of cases. The first sign of toxicity usually precedes the other side effects by 1–3 days. Fever, gastroenteritis and phlebitis at the site of injection were toxic signs of minor importance. However, to avoid phlebitis the drug should be injected through a tube of a free-running intravenous infusion. Adriamycin seems from the present series to be devoid of significant cardiac toxicity. As expected, children tolerated higher doses than adults and all pretreated patients became rapidly intoxicated with small doses. The less toxic schedule appears to be the intermittent one (C). Prompt and consistent responses were observed in many cases (table 4), but they were usually short lived. The drug appears therefore to be a potent growth-inhibiting compound more useful for inducing the first remission than for mantaining it. Acute lymphoblastic and chronic myelogenous leukemias as well as malignant lymphomas, neuroblastomas and soft tissue sarcomas were the diseases most sensitive to adriamycin.