Continuous intravenous infusion of chemotherapy is now widely used to enhance the therapeutic index of cancer drugs. Cellular kinetics and pharmacological basis for protracted intravenous chemotherapy are reviewed for the main available drugs. From the increasingly published data it is now possible to separate routine and research utilization of protracted infusion chemotherapy.

Six antitumoral drugs were tested in human lymphocytes cultures. Our observations pointed out specific abnormalities beside more usual chromosomal aberrations. These lesions are mainly telomeric and chromatidic fusions, chromomerisations and despiralizations. We present an interpretation of these abnormalities.

Treatment of Rous Sarcoma virus transformed chick embryo fibroblasts with 1 mM 5'-deoxy-5'-S-isobutyladenosine for 24 hrs. leads to the inhibition of transforming virus production. A kinetic analysis of the inhibition of active virion production revealed that the effect of the drug was time and concentration dependent. After 24 hrs. with 1 mM SIBA, the production of transforming virus was inhibited 165 fold. However, under these conditions there was only a 2 fold inhibition in viral particle production. Thus, these viral particles were either non infective (non adsorbed on cell membrane) or non transforming. The majority of viral particles produced by cells cultured with the drug have a decreased density. Analysis of these virions showed a decrease of protein P19 and an accumulation of proteins with high molecular weight.

Six hundred and eighty seven cases of cancers of various sites, essentially of squamous structure are presented. Their treatment consisted of a combination of cisplatinum, given 5 days in a row every 3 weeks and of continuously infused bleomycin, also 5 days every 3 weeks. Objective (greater than 50 p. 100) regressions were seen in 70 p. 100 of cases, a significantly greater proportion than obtained by other chemotherapies or by cisplatinum and bleomycin given for one day. This difference is attributed to the fact that bleomycin, a potent inhibitor of type II DNA polymerase, inhibits DNA repair. The authors evaluate the extent of DNA repair to be about 80 p. 100 of all the lesions created by platinum salts and consider DNA repair to be a major limitation of cytostatic therapy, often neglected in the design of chemotherapy protocols.

The effects of elliptinium were studied: Firstly, in the dog, in comparison with the effects of histamine, on heart rate and arterial blood pressure. Secondly, in guinea-pig isolated atria. When smaller doses were used (0.375; 0.75; 1.5 mg/kg) elliptinium only induced variations of heart rate. With the dose of 3 mg/kg hypotension and tachycardia appeared. The time-course of these effects was different from that of histamine (5 micrograms/kg): later onset and longer duration. Elliptinium was inactive in isolated guinea-pig atria, as observed in tracheal or digestive isolated smooth muscle. Thus, the cardiovascular activity of this antitumoral agent seems to implicate an indirect mechanism of action. This result is in accordance with the previous results obtained on bronchopulmonary system.

Autologous bone marrow transplantation is a new technique in which some of the patient's bone marrow is removed and frozen to be reinjected later after heavy chemotherapy and/or total irradiation. Applied to solid tumours, this technique makes it possible to use tumoricidal agents to a degree never achieved before. In acute leukaemias bone marrow can be taken during complete remission, cleared in vitro of contaminating blast cells and reinjected after heavy chemotherapy and/or total irradiation have been given to consolidate the remission. The preliminary results of international trials indicate that this new approach to the treatment of acute leukaemias should substantially prolong the first complete remission and most probably increase the cure rate. The different methods used for in vitro depuration of leukaemic bone marrows (e.g. chemotherapy, monoclonal antibodies, immunotoxins) are described.

The renal toxicity of antitumoral drugs is an increasingly disturbing problem. These drugs are now prescribed in an ever wider variety of cases, and delayed renal reactions, previously unknown, are revealed by the longer survivals obtained. For a number of years, patients whose cancer had been cured have been placed under haemodialysis on account of drug-induced renal failure. The renal toxicity of cisplatinum, nitrosoureas and methotrexate is well-known, but mitomycin C is also capable of inducing permanent renal failure; the delayed toxicity of this drug explains that it has long been underestimated. This example emphasizes the need for close co-operation between oncologists, nephrologists and pharmacologists in order to determine, for each patient, the most effective treatment with the minimum of side effects.

Thirty-eight children, followed in the pediatric Department of Institut Gustave-Roussy, developed second malignant neoplasms. Intervals between the two neoplasms ranged from 1 to 26 years. The second neoplasms were defined as having a different histologic diagnosis than the first ones: osteosarcoma, fibrosarcoma, thyroid carcinoma, leukemia were the most frequent second neoplasms. The potential carcinogenic part of chemotherapy and radiotherapy is emphasized. In addition, some genetic susceptibility may enhance the carcinogenic effects of therapy. Nevertheless the incidence of second malignant neoplasms is low. Its estimation is discussed here.

Changes in mean corpuscular volume (MCV) were studied in cancer patients. Vitamin B12 or erythrocyte folate deficiencies were observed in only 9% of macrocytic patients (MCV greater than or equal to 100 fl). Bone marrow study in seven macrocytic patients with normal hemograms and normal levels of vitamin B12 and folic acid, on per os daily cyclophosphamide single agent therapy, showed myelodysplastic features. The highest MCV and MCV increases during therapy among 203 patients were observed in those cancers and cytotoxic therapies most commonly followed by secondary leukemia: Hodgkin's disease treated with MOPP and radiotherapy, and multiple myeloma and ovarian cancer treated with Melphalan. 21 patients who developed secondary leukemia had a higher MCV and a greater MCV increment than the control patients. Differences were significant in Hodgkin's disease. This preliminary report strongly supports monitoring MCV changes during cytotoxic therapy to attempt identification of patients at high risk of secondary leukemia.