Chemotherapy of epidermoid bronchial cancer maintains, despite numerous therapeutic trails, a minimal efficacy and is shown to have no important effect on the duration of survival. Conversely, the immediate results obtained by chemotherapy for small cell carcinoma are remarkable particularly for the localised forms; there are numerous active drugs which can be usefully combined with radiotherapy to increase the level of complete remission and to attempt to influence the eventual outcome which remains unfavourable. However, this chemotherapy should benefit from the multiple research programmes which are currently underway to reinforce the effects of chemotherapy (new combinations of effective cytotoxic drugs, and the potential for changing biological responses) and to improve the techniques of application (for example, continuous infusions and chronomodulation). The intensification of chemotherapy (with or without the use of marrow transplants) seems to constitute, by the reduction of tumour mass that is induced, a factor determining the improvement in long-term results but is still limited only to small cell carcinomas.

Nowadays the palliative treatment of hepatic metastasis very often uses the hepatic arterial chemotherapy in subcutaneous injection cavity. Unfortunately in about ten per cent of the cases, the thrombosis of hepatic artery limits the lasting quality of use of the catheters which last about twelve months (more or less four). As mentioned in our observation, if the patient "answers" the chemotherapy, we propose reusing this thrombosized artery by means of an original technical artifice. In this observation, in fact, we grafted a small segment of submesenteric vein on the hepatic disobstructed artery. We think that this artifice could also be used in case of anatomic variations of the hepatic artery like trifurcation.

From june 1983 to december 1987, 441 direct accesses were implanted, 237 intravenous, 51 intraperitoneal and 153 intra-arterial. The surgical procedure, the indications, the post-operatory and later complications and the issue of the direct intravenous accesses implanted by the same surgical team are presented. 237 direct access implants were placed intravenously in 228 patients. There are many indications for implanting direct access: absence of a superficial venous network, continuous chemotherapy, preservation of the superficial venous network, thrombosis of the hepatic artery after, inoperable hepatic metastasis (jaundice). Direct venous access was implanted for many pathologies essentially for breast cancer (120 cases), large bowel cancer (36 cases). Surgical procedure for direct intravenous access is easy with catheter's control with fluoroscopy monitoring. Only rarely did any later complication occur when using the direct intravenous access (12 cases) representing 5% of all complications. Certain precautions should be taken to reduce the number of complications. Prophylactic antibiotic therapy, surgical procedure for implanting the direct access excision of excess fatty subcutaneous tissue, minutious skin disinfection, heparinization, avoid using the chamber for blood sampling, use intra-arterial direct access. Direct access is used either for sequential chemotherapy or for continuous protocols which vary in length.

In this review paper, the authors summarize the studies which support the theory that a defect in production of energy by the myocardial cells is a determinant factor in the genesis and/or aggravation of dilated cardiomyopathy. Points that are common to this metabolic theory and to the other pathogenetic mechanisms usually described (notably viral or toxic mechanisms) are presented.

Prodrugs are pharmacologically inert and nontoxic chemical compounds which are transformed in vivo into pharmacologically and therapeutically active compounds, i.e. drugs. Prodrugs are used to solve problems which cannot be solved by the drugs themselves. There are three types of problems: problems arising before the drug enters the body (solubilization, stabilization and improved acceptability); problems associated with the penetration and fate of the drug in the body (absorption, barrier crossing, duration of action); problems relating to the therapeutic target (selective local delivery). The principal prodrugs that solve these problems and the mechanisms of the solutions they provide are described and discussed.

The results of surgery as sole treatment of colon cancer are summarized before dealing with those of chemotherapy. Curative or palliative chemotherapy remains controverted. The results of single drug treatments and of the conventional protocols with 5-fluorouracil and nitrosoureas have been disappointing. A promising approach is modulation of 5-fluorouracil by folinic acid, with a response rate of up to 45 p 100, and potentiation of 5-fluorouracil by cisplatin. Intra-arterial chemotherapy has been, and still is, an interesting method in liver metastases, but recent studies and the experience acquired with prolonged follow-ups have thrown doubts on some of its results, notably survival. Adjuvant chemotherapy is even more controversial than curative chemotherapy; however, a recent controlled study has yielded favourable results, and the best drug combinations have not yet been tested. It is concluded that cancers of the colon have shown some chemosensitivity, even though it has not reached the same level as that of cancers of other organs.

The pharmacokinetic studies of anticancer drugs still go on after they are out on the market. The therapeutic protocol is then more precise and depends on the dosage results of these drugs. Some examples of dosage adjustment according to their plasmatic level are reported here for high-dose methotrexate infusion and for CDDP infusion over five days. The test dose and the bayesian method (pharmacokinetic population) are used to predict the adapted individualized dosage for each patient.

Animal extrapolation of antitumor drug pharmacokinetics deals with either the determination of equations describing drug disposition or the determination of physiological parameters governing this distribution. Papers on this subjects show the need for numerous animal species to predict quantitative evolution curves and the lack of precision in the obtained results. Practical interest of such studies is limited since the pharmacokinetic parameters are systematically evaluated in man during phase I trials. On the contrary, analysis of the mechanism of drug distribution cannot be performed without interspecies scaling to evaluate physiological parameters which are not measurable in humans.