Phytochemical and pharmacological studies on Taxus sp extracts have resulted in the isolation and the identification of several diterpenoids, and the discovery of the potent antitumor activity of taxol. This natural compound displays a unique mechanism of action as it stabilizes microtubules and inhibits their depolymerization into free tubulin. The emergence of taxol from the screening of natural products shows the benefits and the potent interest of these constituents in the search of drugs exhibiting novel mechanisms of action. The most pressing problem in taxol or taxol derivates commercialization is the drug supply. Alternative sources of taxol are now under investigation, mainly the total synthesis of taxol, the hemisynthesis of taxol or of taxotere from 10-deacetylbaccatine III, the in vitro production of taxol by cell or tissue cultures, and the prospection of new natural sources of taxol.

One of the best known iatrogenic effects of anticancer treatments is the sterility of young patients with a good prognosis, hence the necessity to develop a protocol enabling us to preserve male reproductive function. This review of the literature summarises the various approaches investigated in order to obtain protection of spermatogenesis prior to radiotherapy and/or chemotherapy. Most of these pathways involve hormone therapy based on regulation of the hypothalamo-hypophyso-testicular axis. Animal models are generally used in these experiments. The various applications in man are described and discussed.

We evaluated the efficacy and safety of piperacillin-pefloxacin potentially associated to vancomycin as a non nephrotoxic antimicrobial therapy in febrile neutropenic cancer patients, treated with nephrotoxic chemotherapy. Fifty-seven patients: 49 with solid tumors and 8 non-Hodgkin lymphomas, were treated during 85 episodes with: piperacillin 4 g IV every 8 h pefloxacin 400 mg IV every 12 h. If the patient remained febrile after 72 h, 1 g of vancomycin IV was added every 12 h. The mean duration of neutropenia was 7 days (3-14 days). In 44 episodes, the granulocyte nadir was < 100/mm3. Infection was microbiologically documented in 17 episodes (20%) with ten Gram-positive cocci and 11 Gram-negative bacilli. There were 64 apyrexia with piperacillin-pefloxacin (75%) and further 14 were resolved by the addition of vancomycin (total success = 92%); three early changes because of clinical deterioration (two episodes) or germ resistance (one episode); three protocol violations, and one apyrexia by addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and avoids nephrotoxicity in cancer patients heavily treated with nephrotoxic chemotherapy.

Programmed cell death, or apoptosis, corresponds to a sequence of intracellular events that lead to cell death. It has been shown that apoptosis is necessary in some physiological conditions such as embryogenesis, homeostasis of the immune system, erythropoiesis, etc. Some xenobiotics can induce apoptosis at lower doses and necrosis at higher doses. When a cell dies, it is either by apoptosis or by necrosis, and there are many differences between these two deaths. Apoptosis begins by a pre-commitment phase, which is reversible; during this phase the cell has a high level of second messengers. The commitment phase then follows and is irreversible, even when the xenobiotic that triggered the induction is removed. Most often, apoptotic cell death requires synthesis of macromolecules, the inhibition of their synthesis can prevent it. The cell undergoes important morphological changes during apoptosis, its volume decreases when its density increases. Then chromatin becomes granular, intensively osmiophilic, it condenses along the nuclear membrane. Later, chromatin disintegrates into small granules which will be phagocytized. One of the most important characteristics of the programmed cell death is the activation of an endonuclease, that gives rise to DNA fragments of 180-200 base pairs or multiples of these numbers; then after electrophoresis, the DNA gives the appearance of a ladder. Apoptotic cells can be characterized after classic staining, and flow cytometry; they can be separated from other cells by centrifugation on a gradient of density. It has been hypothesized that cell transformation could be due to a sudden resistance to apoptosis. However, the most interesting aspect in oncology recently demonstrated is that well-known anticancer drugs are able to induce apoptosis. One can hope that the discovery of new targets for anticancer drugs could lead to discovering new drugs that could be more active.

The biological activity of spindle poisons can easily be measured using an in vitro assay based on the interaction of these substances with their cellular "receptor": tubulin. The use of this assay led us to select Navelbine and Taxotere as antimitotic substances. These compounds, as well as their natural parents: vincaleucoblastine, leurocristine and taxol respectively, have been obtained by semi-synthesis using relatively abundant natural precursors as starting materials. This paper summarizes the preparation of these important anticancer drugs.

Nurses are exposed to a variety of risks while handling cytotoxic drugs. A study was conducted in 6 different hospitals where those drugs are used. We inquired about the nurses information about their possible toxicities and the protection measures used while preparing and giving these drugs. The results showed that 50% of the 43 nurses questioned don't have complete information about these toxicities and nearly 60% of them do not apply any preventive measure for safe handling of the drugs especially the use of disposable gloves, the use of coveralls with long sleeves and the use of protective glasses.

The development of new chemotherapeutic protocols especially those cisplatin containing regimens, has lead to a dramatic improvement of remission rates in certain cancers. Nausea and vomiting seems to be the most distressing side effect from the patients point of view. A good administration of classical anti-emetic drugs should yield to at least 50% of good protection. The introduction of new drugs should even give more protection to our patients.

Activation of coagulation and of the fibrinolytic system has been identified in small cell and non-small cell cancers respectively. For the clinician this poses the diagnostic problem of a thrombosis, which is most often venous with or without pulmonary emboli, complicating the evolution of an already diagnosed cancer. The inverse is that these features may reveal an underlying neoplasm and amongst the most common of these would be bronchopulmonary cancer. Numerous laboratory studies have shown the existence of a state of hyper-coagulability, with disseminated intra-vascular coagulation, which is more or less compensated and is the more marked, the more advanced the cancer is. One should not fail to recognise that this state of hyper-coagulability may be aggravated by certain cytotoxic drugs. At the level of the tumour itself, there seems to be interactions between the cancer cells and the coagulation and fibrinolytic system: these interactions are very different according to the histological type as to whether they are small cell or non-small cell bronchopulmonary cancers.