Notes: Summary The anthracyclines, of which daunorubin (DNR), rubidazone (RBD), and adriamycin (ADR) are the most commonly used in cancer chemotherapy, belong to the group of intercalating agents capable of inhibiting the replication and transcription of DNA, and of fragmenting DNA and inhibiting the mitochondrial respiratory chain. Their experimental antitumoral activity varies according to the product, the type of tumor, and the route of administration. Following intravenous (IV) injection, they are distributed throughout all body tissues except those of the central nervous system and are metabolized principally in the liver, 90% of the metabolites being excreted in the bile. Excretion is slow, permitting intermittent high-dose therapy. Their principal toxicity is cardiac, presenting as congestive cardiac failure, which occurs when a specific cumulative dose of anthracycline is exceeded. This effect may be due to the formation of free semiquinone radicals from the anthracycline nucleus by the capture of electrons from the mitochondrial respiratory chain. Only a few of the most active derivatives have been studied in man and the search continues for active agents devoid of cardiotoxicity. The therapeutic indications vary according to the derivative. DNR, which we have utilized since 1967, is remarkably effective in induction therapy for acute myeloblastic leukemia, is the only agent which is effective in acute promyelocytic leukemia, and increases the number of complete remissions in acute lymphoblastic leukemia in the adult and in severe childhood forms of this disorder. ADR is active against solid tumors (thyroid, breast, osteosarcoma) and also against lymphomas. RBD induces a complete remission in two-thirds of the cases of acute monoblastic leukemia, is equally as effective as DNR in acute myeloblastic leukemia, and is significantly more manipulable. This agent may similarly induce a remission in the severe lymphomas (lymphosarcoma and Hodgkin's disease). A new semisynthetic compound, DEA.14.DNR, appears promising. Experimentally it compares favorably with the other anthracyclines and clinically demonstrates potential against solid tumors.

Notes: Summary The complete hematological remission (CHR) rate, duration of remission and survival were studied in relation to age, peripheral blast cell (PBC) count, presence or absence of tumor masses, cytological type, and treatment in 650 patients with acute lympho-blastic leukemia. Prognostic factors were considered separately and divided into prognostic classes. Age and PCB count correlated with both the rate and the duration of CHR. This correlation was still observed for more recent treatment schedules though it appears to be becoming progressively less significant. Meningeal relapses were more common in patients less than 1 year old and in those with a high PCB count. It is suggested that stratification of patients according to such factors as age, PCB count, presence or absence of tumor, and cytological type might be necessary for the design of new treatment protocols and for the evaluation of their results.