Trehalose dimycolate (TDM), a well-defined component of Mycobacterium tuberculosis cell wall has been tested in vivo and in vitro for its effect on the tumoricidal activity of Rat peritoneal macrophages. Macrophages could be rendered cytolytic against syngeneic tumor cells by an intraperitoneal injection of an aqueous suspension of TDM. However, as we failed to render them tumoricidal in vitro, we consider that the activation process is not due to a direct effect on macrophages.

The cardiotoxicity of the anthracyclines, of which doxorubicin is the leading drug, manifests itself in two ways: acutely, giving rise to temporary and usually benign phenomena, and chronically, giving rise to cardiac failure which is often irreversible. The risk of cardiomyopathy is related to the total dose of anthracycline administrated. The main risk factors are, age, previous cardiac disease and mediastinal radiotherapy. The prevention of cardiomyopathy is based on the respect of empirical guide lines (interruption of anthracyclines at "threshold" cumulative doses) and on methods of detection of infra-clinical disease. Myocardial angioscintigraphy which is easier to perform than myocardial biopsy and more sensitive and specific than echocardiography seems to be the investigation of choice. The main lines of research are aimed at improving our understanding of the mechanism of the cardiomyopathy, the institution of clinical trials to detect the first signs of toxicity of continuous infusions, the improvement of the standardisation and specificity of methods of detection, better definition of alarm thresholds and the development of new, less cardiotoxic, anthracyclines and cardioprotective agents.

Adjuvant antimitotic chemotherapy increases the survival rates of patients suffering from breast cancer with nodes involvement, but its effects on the immune status are still unclear. The immune status of these patients was studied from the general point of view and particularly from the antitumoral immunity. The most studies which have been made, indicated a such immunity was present, and proved it was more important when the tumor's invasiveness is limited without node involvement. From a general point of view, when an immunologic impairment is present in patients with breast cancer, it seems to have a poor prognosis. Many modulations of this immune status are determined by the treatment's modalities: surgery and radiotherapy have more or less local or general immunologic effects and in certain conditions, antimitotic chemotherapy is immunosuppressive, but it may also interfere as an immunoregulator with a good effect on antibody secreting cells or on suppressive cells. Several situations may be considered according to the tumor immunogenicity and the host immunologic competence. In these different cases, immunotherapy is not always indicated and when this one is, its specificity is still not sufficient. The recent results of specific or non specific immunotherapy trials performed after locoregional treatment or antimitotic chemotherapy are generally not significant and do not lead us to propose a modulation of immune status without controlled trials.

Results of a phase II clinical trial of vindesine sulfate in differentiated carcinoma of the upper respiratory and digestive tracts demonstrated good efficacy, with 6 objective responses in the 14 patients with interpretable reports several toxic reactions were observed, three patients developing polyneuritis of the upper and lower limbs after doses of 33 to 40 mg of DVA. Hematologic toxicity was moderate and regressive.

Contrarily to that which has been observed in some experimental tumors, the clinical data show that it is not possible to take advantage of the semi-synchronisation of tumor cells induced by the administration of cytotoxic drugs or ionizing radiations, either in combination chemotherapy or during the association between radiotherapy (RT) and chemotherapy (CT). The association of RT and CT has obtained excellent results in those human tumors which are both chemosensitive and radiosensitive such as lymphoma, testicular tumors, embryonal tumors, cancers of childhood. However, even in these favorable types of tumors, high doses of RT and CT are required, not significantly lower than those which are delivered when one of the two modalities is used alone. Therefore, the major problem is that of the possible cumulative toxicity of the two modalities. The toxicity appears to be maximum when the two modalities are administered concomitantly; it can be reduced in sequential administration when there is a sufficiently long interval between the various agents. However, sequential associations may cause long delay in the delivery of one of the two modalities and in rapidly growing tumors this delay might be detrimental. This is why an integrated alternating scheme was proposed in which short radiotherapy courses are interdigitated between the courses of chemotherapy, chemotherapy being administered with the conventional scheduling. Preliminary results of this alternating combination are discussed. In small cell carcinoma of the lung and non-Hodgkin lymphoma of poor histologic types, so far the results are promising.

One hundred and thirty three specimens from mammary and ovarian adenocarcinoma and from melanoma were cultured according to an agar/agar clonogenic assay. Melanoma and ovarian cancers exhibited a 70 per cent rate of success for culture; 50 per cent of the mammary adenocarcinomas were successfully cultured. Fifty-nine ovarian cancers were cultured in order to test the in vitro effectiveness of Cisplatinum and Adriamycin. Thirty percent of cultured tumors gave rise to relevant chemograms. The chemoresistance measured in vitro was correlated to the ineffectiveness of the patient's treatment. In contrast, we were unable to predict chemosensitivity. Taking into account the technical difficulties encountered in these assays, human tumor clonogenic assays cannot at present be proposed as a routine procedure in the prediction of the effectiveness of chemotherapeutic treatments. Nevertheless, they must be developed in order to determine the spectrum of activity of new antineoplastic agents on various human tumors.

It now seems possible to predict response to anti-cancer drugs by means of several methods classified into three groups. Methods in the first group are aimed at determining the intracellular mechanisms required for the drugs to act on the tumoral cells; apart from hormone receptor assays, few of these have practical applications. Methods in the second group are concerned with the action of cytostatic drugs on malignant cells; clonogenic cultures and human tumour xenografts in mice are already routinely used. Finally, methods to evaluate the pharmacokinetics of anticancer drugs are being developed. These three groups of methods can be used in the pre-clinical screening of these drugs or at the clinical trial phase to predict individual responses to chemotherapy.

Twelve patients with non-Hodgkin malignant lymphoma of poor prognosis were treated with heavy chemotherapy of the TACC type (cyclophosphamide 45 mg/kg/day i.v. X 4; cytosine arabinoside 200 mg/m2/12 hours i.v. X 7; 6-thioguanidine 100 mg/m2/12-hourly p.o X 7 and CCNU 200 or 250 mg/m2 p.o. single dose) followed by autologus bone marrow transplantation (853 to 20.000 CFUc/kg). The patients were divided into 2 groups depending on whether they received an induction treatment for large visible tumoral mass (group I: 3 initial presentations, 3 relapses) or a consolidation treatment for small residual tumour (group II: 6 complete and 1 partial remissions). The results show that autologous bone marrow transplantation shortens the duration of the therapeutic aplasia. White cell (greater than 10(9)/l) and platelet (greater than 50.10(9)/l) recovery was observed on days 12 (range 9-19) and 14 (range 8-27) respectively. In group I, 1 patient died of myocardial TACC toxity and acute renal failure on tumoral kidney; there were 2 failures and 3 complete remissions (8, 21, 45 + months). Remissions occurred in patients treated initially; the overall survival since diagnosis was 48+, 48+ and 60+ months. In group II patients there were 1 failure and 5 complete remissions persisting after a 2+ months to 30+ months follow-up; the overall survival was 23+, 24+, 27+, 42+ and 70+ months. The 3 failures in the series occurred in circumstances suggesting contamination of the cryopreserved bone marrow by tumoral cells. The toxicity, largely due to infection, of the TACC-bone marrow transplantation combination was tolerable. It was clearly lower in group II (6 patients, no septicaemia) than in group I (5/6 patients with septicaemia). These preliminary results confirm that there is room for autologous bone marrow transplantation in highly malignant non-Hodgkin lymphomas, particularly during complete remissions to facilitate the use of an aggressive consolidation chemotherapy.

Nephrocalcinosis due to hyperphosphataemia with hypocalcaemia is a rare cause of ARF during chemotherapy of ALL. Three cases are reported, one with renal anatomopathological studies and microanalysis of the intratubular calculi. All possible preventive measures should be taken against this complication which is related to acute tumoral lysis, especially in the hyperleukocytic and/or tumoral forms of ALL.

Infection is the leading cause of illness and death in children with leukemia. The risk of infection may change over time as regimens of therapy are modified. A review of the hospital charts of 166 infants in whom leukemia had been diagnosed between 1976 and 1980 revealed an increased number of deep fungal infections (20 v. 3) during this period in comparison with the number between 1969 and 1976 in 164 patients treated at the same hospital whose leukemia was diagnosed between 1969 and 1975. The 20 severe fungal infections between 1976 and 1980 were characterized by difficulty of diagnosis (a definite diagnosis having been made three times out of four only at autopsy), an important role of Candida but also of Aspergillus (the latter having been isolated almost as often as the former) and a grave prognosis (the mortality being very high [75%] and much above that for gram-positive septicemia [6%] and that for gram-negative septicemia [31%]). This increase in frequency of fungal infections was concurrent with the introduction of phase-1 chemotherapy, which was often responsible for prolonged neutropenia. To reduce the risk of infection in children with leukemia it appears to be essential to improve diagnostic methods and approaches to therapy.

A system employing a micro-balloon catheter is proposed for the introduction of catheters for intra-arterial chemotherapy.

Some aspects of the relationships between malignancy and rheumatic diseases are presented. The incidence of leukaemia and lymphomas is increased in rheumatic patients previously treated by alkylating agents or x-rays; hypertrophic treated by alkylating agents or x-rays; hypertrophic osteoarthropathy is frequently associated with bronchogenic carcinoma; very exceptionally, rheumatoidlike arthritis or polymyalgia rheumatica may be paraneoplastic syndromes. As a rule there is an interval of as long as several months between the beginning of joint or bone pains and radiological appearance of metastases. Early detection is possible if there is an elevated level of alkaline phosphatase, increased excretion of hydroxyproline and a positive bone scan.

Acute lymphoblastic leukemia (cytologically typical) was diagnosed in an 18-year-old man presenting with major eosinophilia. Prednisone therapy was initiated but sudden congestive heart failure occurred (left ventricular insufficiency with pulmonary edema). Concomitantly, blood counts became normal. Remission of the leukemic process was obtained while severe mitral regurgitation developed, due to bacterial endocarditis. Successful mitral valvuloplasty was achieved. Remission is still persisting one year after diagnosis.