It is reported a case of long-term Hodgkin's disease treated with several courses of radiotherapy and chemotherapy and complicated with acute myeloblastic leukemia. Authors discuss the responsability of treatment immunosuppression, viral infections, levamizole and genetic factor.

Little is known about the late effects of damage to the gonads in children treated for cancer. This investigation requires a prolonged surveillance. Radiotherapy sterilizes the ovaries above a dose of about 500 rads in an adult. Therefore, to protect at least one ovary in partial irradiation of a child's abdomen in mandatory whenever possible, either by restriction of the irradiated volume, or transposition of the ovary. Combined chemotherapies do not seem to inhibit endocrine function but it is too early to appreciate the effects of different combinations of drugs on reproductive function in girls. In boys, alkylating drugs cause an oligo or azoospermia, either temporary or permanently. The genetic risks in the descendants of children treated for cancer are still unknown.

The risks of embryonic, fetal, gondal damage of cancer chemotherapy are reviewed. Contrasting with the numerous malformations seen in laboratory animals, the teratogenic risk is low in man. Methotrexate is really dangerous during the first trimester of pregnancy. In malignant haematological diseases and solid tumours, the prognosis of the disease is the essential target but the use of immuno-suppressive drugs in non-malignant diseases is hazardous before 40 years of age. All the investigations show that alkylating agents injure the gonads. Young women should be avised to use contraceptives. The future of children born after administration of anti cancer drugs is uncertain. Sterility, carcinogenic risk, mutation, teratogenetic effects in future generations cannot be ruled out.

Golden hamsters were submitted to i.p. administration during 4 weeks of 8 anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), adriamycin hydrochloride (ADMh), rubidazon (RBZ), aclacinomycin (ACM) and AD32, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. The comparative study of the mortality, the electron microscopic (EM) alterations of the myocardium, and the light microscopic (EM) alterations of the myocardium, and the light microscopic (LM) lesions of the skin, show that ACM and AD32 are the least toxic drugs. EM detected almost no early lesions of myocardium in ACM treated animals, but, after 4 week's treatment, severe cardiac alterations appeared which, like those after AD32 treatment, are non lethal and reversible. Similarly. LM revealed no histologic changes in the skin following ACM and AD32 administrations, but pathologic alterations, atrophy and alopecia, were observed in animals receiving all other drugs.

1) The in vitro effect of virus-inhibiting factor (IF) or interferon on Ehrlich ascites tumor and sarcoma 180 was found to be cytostatic, but not cytocidal. 2) Mouse peritoneal macrophages or splenic lymphoid cells, in the presence of IF, did not affect multiplication of the tumor cells examined.

Twenty five cases of Hodgkin disease were treated by chemotherapy and radiotherapy after staging laparotomy. The safety and the utility of staging laparotomy are discussed. Staging laparotomy seems to be usefull in stage II with involvement of at least three lymphatic territories and in stage III.

Anthracyclines, such as daunorubicin (DNR), rubidazone (RBD) and adriamycin (ADR) are intercalating drugs used in cancer chemotherapy. They inhibit synthesis of DNA and RNA, break DNA and inhibit mitochondrial oxidative chain. Their antitumoral experimental activities depend upon type of drug, tumor and route of administration. After i.v. administration, the drug is present in all tissues except central nervous system. Its disappearance from the plasma is biphasic with a long terminal half life, justifying intermittent chemotherapy. Anthracyclines metabolism occurs mainly in liver micrososomes, and 90% metabolites are excreted in the bile. The main toxicity is cardiac, as a congestive heart failure which appears when a cumulated drug dose is overcome. In man only, a few derivatives have been studied, compounds with activity and no cardiotoxicity are still in research. Action of malignancies depends on type of derivative. We use DNR since 1967, it is a remarkable active drug in induction treatment of AML, it is the only active drug on acute promyelocytic leukemia, and it increases number of remissions in all of adult patients and severe forms of children ALL. Adriamycin (ADR) is active on solid tumors (osteosarcoma, breast and thyroid cancers) and lymphomas. With rubidazone (RBD) we obtain 2/3 of remissions in acute monoblastic leukemia, and it is easier to use than DNR and equally active on AML. RBD is also active on severe cases of lymphomas (lymphosarcomas and Hodgkin's disease). A new compound DEA 14 DNR seems interesting: experimental antitumor activity is high (compared to DNR, RBD and ADR) and it appears to possess activity on solid tumors in man.

The synthesis of the N,N-bis-(acetylhomoveratrylamido)-1-hydroxymethyl and 1-carboxypropylamines (III a) and (III b) is described. Until now, these molecules could not been cyclized to the corresponding isoquinoline compounds. An attempted synthesis of 3-azaemetine by condensing homoveratrylamine with acetonedicarboxylic acid or its esters did not yield the expected diamide (XIV). However, by subjecting 1,3-bis-(1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)acetone (XV) to a reducing aminoalkylation, one obtained the corresponding ethylamino derivative (XVI) which could be cyclized through Mannich reaction to give 3-azaemetine. The pharmacological screening showed 3-azaemetine to be less toxic than emetine in the mouse and without antiamebic and antitumor activity against P 388 Leukaemia in the mouse (25).

Rubidazone is a semisynthetic antibiomitotic close to daunorubicin and doxorubicin. Fifty two patients with various advanced cancers received rubidazone intravenously at the initial unitary dose of 200 mg/m2 in a single injection at three week intervals; this base line dosage had been adapted in function of leuko-platelet variations observed between the injections. An objective improvement was noted in 18 patients out of 51 evaluable patients (34% of the cases), 6 times the regression of tumoral volume was greater than 50 per cent but not complete (3 breast adenocarcinomas and 3 lymphomas). Manifestations of intolerance-toxicity were minor on the haematologic side (32%); however, they were relatively frequent from the digestive (63%) and general (82%) point of view; symptoms of cardiac disturbances (21%), responsible for the discontinuation of the chemotherapy, necessitate careful attention in the management of the treatment. The comparison of the results of this trial with those obtained by trials using other drugs belonging to the same chemical family don't show, for solid tumors, any difference in efficacy between rubidazone, daunorubicin or duborimycin; however, the difference is very striking with doxorubicin which showed more efficacy (6.5% as 29% of regression greater than 50%). Owing to the conditions of admission and the very strict criteria of analysis in this study, it would seem useful to go into details regarding the interest of rubidazone in lymphomas (only one failure has been recorded out of 6 treated cases).

Research in the kinetics of cell proliferation directly interests oncologists for fundamental and pragmatic reasons. Since cancer is a perturbation of the control of cell proliferation and differentiation, such research may help to understand, the regulation mechanisms, in particular the role of microenvironment, of long range humoral factors, and of membrane site receptors. Furthermore the kinetics of cell proliferation in a normal tissue, or a tumour, influences its response to radiation or drugs. From this evolves the practical interest in research on hemopoietic tissues and on human and experimental tumors. Finally, the growth kinetics of human tumors explain their natural history and opens prospects for the treatment of intraclinical neoplastic disease and metastasis.

Adding duborimycin to the association of vincristine + DTIC in the treatment of malignant melanoma produces therapeutic results interesting but not statistically significant and not counter-balancing the toxic side effects. This study confirms the lack of positive results of polychemotherapy in melanoma as compared to treatment by an efficacious single drug therapy (DTIC); it also emphasizes the necessity of randomized studies so that valuable comparisons may be done.

The authors report a case of stomatitis, in a patient receiving antimitotic therapy, which was found to be due to an acute leukosis. They feel that patients on antimitotics who develop stomatitis should have a white cell count to exclude leukosis, which is not a very rare finding today.

Extrinsic allergic alveolitis of drug origin is now a better known branch of respiratory pathology. The symptoms and course of these cases resemble in many ways those of extrinsic allergic alveolitis in general with a few differences. The list of drugs responsible is longer every day, and it is important to be aware of it. The diagnosis of these diseases is not always easy, as there are certain similarities between them and other long diseases either iatrogenic or not, but not immuno-allergic. Our physiopathological knowledge is based on already known data concerning allergic alveolitis, but includes many theories which still have to be verified. It is important for the clinician to be aware of this new type of respiratory disease as the treatment includes withdrawal of the responsible drug as soon as possible, failing which irreversible pulmonary fibrosis develops.

RFCNU or (chloro-2-ethyl)-l-(ribofuranosyl-isopropylidene-2', 3' paranitrobenzoate-5')-3 nitrosourea, a new synthetic nitrosourea derivative, which has been shown to have, in mice, among all nitrosourea derivatives tested, the longest maximallly efficient dose interval (MEDI) and which is not immunosuppressive at the smallest dose of MEDI, gave in a phase II trial on digestive tract tumours (at the dose of 400 mg/m2 per month determined by the phase I trial), 30% objective remissions among which 13% were greater than 50%.