Around 3,000 cisplatin analogues have been synthetised over the past 30 years but only half a dozen are presently in clinical development, while only two (cisplatin and carboplatin) have been available prior to the recent European registration of oxaliplatin. Oxaliplatin is a new platinum salt belonging to the DACH (diaminocyclohexane) platinum family, and is the only such cisplatin analogue that has entered clinical development and achieved approval for marketing. During its development, oxaliplatin has aroused lively interest due, firstly, to its in vitro and in vivo antitumoral activity, especially in cisplatin-resistant models and cell lines expressing resistance genes, and, secondly, to its good clinical tolerance, the absence of renal or auditory toxicity being combined with a low hematotoxicity. Combined with other antitumoral agent cytotoxic agents (5FU, raltitrexed, irinotecan or cisplatin), oxaliplatin produces an additive and often synergistic cytotoxic effect. The oxaliplatin-5FU +/- FA combination is now well established in metastatic colorectal cancer. Regarding its particular cytotoxic characteristics and its activity in mismatch repair deficient cells (which are resistant to cisplatin and carboplatin), oxaliplatin is shows potential in a large variety of solid tumor types, notably in association with other cytotoxic agents, thus opening the path to a wider range of indications.

Marked advances in the treatment of non-small cell lung cancer (NSCLC) have been made thanks to new agents. Among these agents, gemcitabine appears to be a major compound in advanced stage NSCLC chemotherapy. To start with, several phase III trials (conducted in Europe and in the USA) studied the gemcitabine/cisplatin combination (GC): US study protocois compared GC to cisplatin alone, to the standard treatment (etoposide/cisplatin) or to platinum/taxane doublets; in these studies, as a result of treatment with GC, a higher survival rate was observed. A study conducted in Italy, which is undergoing analysis, observes GC versus paclitaxel/carboplatin versus cisplatin/vinorelbine. In addition, in newer clinical protocols, it was observed that gemcitabine combined with taxanes or with vinorelbine demonstrated efficacy at least equal to that of combinations with platinum analogs. Newer agents acting on epithelial growth factor are also undergoing evaluation.

Multi-targeted antifolate (MTA) is an anti-metabolite with useful activity in the treatment of non-operable patients presenting with non-small cell lung cancer. Its good efficacy and tolerability profile as first-line therapy was demonstrated in phase II studies of MTA as monotherapy. The use of MTA as second-line therapy with or without a platinum analog also provides good results. It should be observed that, in combination with cisplatin (C), docetaxel or gemcitabine (G), MTA presents synergistic efficacy: two phase II protocols have shown that the MTA/C combination as first-line therapy presented high efficacy (objective response: 39-45%) and low toxicity. These results are promising and also seem to be observed in an ongoing phase II study evaluating MTA/G. In the treatment of mesothelioma, promising activity was observed for the MTA/C combination, and this activity is under evaluation in ongoing phase II and phase III studies.

A direct or indirect effect of the intake of medication on the pulp itself has not yet been described in the literature. The effect of local anesthetics on the pulp, on the other hand, has been documented. Although local anaesthesia has been employed in dentistry for many years, most investigations of its action have only considered the effect on the nerves within the pulp using traditional methods. Recently it has become clear that the nerves and blood vessels of the pulp do not act in isolation but are closely related. In this respect it has been shown that there exists a direct relationship between the length of the flow cessation and the concentration of vasoconstrictor used. Therefore care should be taken when using vasoconstrictors especially where pulpal injury is apt to occur when dental procedures such as full crown preparations are performed immediately following a ligamental injection. The anaesthetic efficacy of intraosseous injection is well documented. The effect, however, on the dental pulpal circulation still remains subject of further investigation. Radiotherapy involving the oral cavity and salivary glands and chemotherapy (in a lesser degree) induce alterations in the oral tissues and the salivary gland functions. Some of these side effects are transient. However there are side effects such as the xerostomia which are very drastic for the dentition resulting in radiation caries and dental hypersensitivity. Tooth anomalies in the developing dentition are also described. Due to the rapid progression of the radiation caries a monitoring of the oral cavity with strict application of preventive measurements and systematic follow-up can reduce the incidence of the complications. Unfortunately most of the patients belonging to this group consult with the complications of their radiotherapy and chemotherapy. In this respect endodontic treatment of the severely decayed teeth is an important part of dental treatment. Moreover, extraction is regularly contraindicated as osteoradionecrosis is then one of the major sequels.

To compare by a prospective study in low risk polycythemia vera (PV) patients alone two drugs: hydroxyurea and pipobroman. Toxicity, efficiency, and leukemogenic potential were studied.

To define pathogenesis, incidence, clinical presentation and prognosis of leukemic transformation (LT) in patients with essential thrombocytemia (ET); to compare the incidence of LT in previously treated versus untreated patients; to search for risk factors of LT, with special reference to the iatrogenic risk of myelosuppressive drugs.

Drug-induced fever is a frequent (3-5% of all adverse effects) but under recognized adverse effect of several drugs. Hydroxyurea, an antimetabolite cytostatic agent, has rarely been involved in the occurrence of fever. We report three additional cases of hydroxyurea-induced fever including one case with pulmonary involvement (acute alveolitis). In these cases, the role of hydroxyurea was strongly suggested by the delay to onset of symptoms (16-36 days), the disappearance of fever within a few hours after drug withdrawal, the recurrence of fever shortly after rechallenge in two patients, and the absence of any other obvious cause.

Chemotherapy administered during childhood may induce dental abnormalities, such as acquired amelogenesis imperfecta, microdontia, hypodontia and altered root morphology. The magnitude of the defect varies according to the cytotoxic agents, the duration of their use and the stage of tooth development at the time of chemotherapy. Patients who received high-dose chemotherapy before the age of 5 are particularly concerned. The dental supervision of these children is based upon three orthopantomograms: the first one has to be performed before starting chemotherapy and will be used as a reference; the second is done soon after the drug therapy in order to evaluate the first consequences; the third is performed after the eruption of all permanent teeth (age 12-13 in average) in order to determine the dental abnormalities. In case of hypodontia, orthodontic treatment must be considered, but it is necessary to take into account the fact that it may increase the risk of root resorption. Preventive dental care is important for these children. It involves meticulous oral hygiene and frequent dental visits to assess and maintain dental health.

Phase I clinical trials consist in studying tolerance to new drugs administered for the first time to humans, the pharmacodynamics of these drugs in order to describing as clearly as possible their pharmacological mechanism of action, and their pharmacokinetics in order to determine the metabolic and excretory pathways involved in the human organism.

Damage to local and systemic host defenses of the lung makes the immunocompromised patient vulnerable to inhaled microorganisms. When a pulmonary infiltrate occurs, the array of possibilities is very large including conventional and opportunistic agents. The type of underlying disease and its associated immunodeficiency allow a high degree of accurate pathogen prediction. Neutropenia is associated with Gram-negative bacilli pneumonia. Prolonged neutropenia increases the risk of invasive aspergillosis and other unusual mycotic agents. Cellular immunodeficiency is associated with intracellular microorganisms including Mycobacteria spp., Nocardia spp., Legionella spp., Rhodococcus equi, cytomegalovirus, Strongyloides stercoralis, Toxoplasma gondii, Histoplasma capsulatum, Coccidioides spp., Cryptococcus neoformans and Pneumocystis carinii, parasites such as Toxoplasma gondii and Strongyloides stercoralis, and virus such as cytomegalovirus, Herpes simplex or zoster, adenovirus, respiratory syncitial virus and measles. Humoral immunodeficiency predisposes to infection with encapsulated pathogens such as S. pneumoniae and Haemophilus influenzae. Chest computerized tomography scan and bronchoalveolar lavage are essential procedures for diagnosis. However, despite continuous progress in diagnostic methods, the specific etiology remains often unknown. Successful treatment depends on the type of pathogen, status of host defences and early adequate choice of antibiotic. Enhancement of host defences with growth factors and cytokines may decrease the incidence and improve the final outcome of respiratory infections in the immunocompromised host.

In order to evaluate occurrence and risk factors for wound infection (WI) in head and neck uncontaminated surgery, we carried out a prospective study.

A 4-week interval between radiotherapy and gemcitabin chemotherapy is recommended due to the risk of severe radiosensitization. Gemcitabin can also have severe lung toxicity late after or without prior radiotherapy.

Cancer chemoprevention envisions a reduction in the incidence of the disease through direct action using various chemical products. Chemoprevention trials involve healthy subjects, as a consequence careful ethical consideration must be given to such interventions. The classical contract between the patient and his doctor is altered in this situation and the numerous consequences of extrapolation of results to the general population must be considered. In particular a calculation of the risk-benefit ratio must take into account not only the physical but also the mental and social well being of people whose lives will be medicalised as a result of such intervention. The primacy of collective benefit over individual interest mandates that chemoprevention be based on scientific and well conducted trials. When results are extrapolated to the whole population an evaluation process has also to be permanently performed. The target population must be well informed and the participation based on voluntary consent.

Cyclin-dependent kinases (CDKs) are widely involved in regulating the cell division cycle. The discovery of numerous alterations of CDKs, cyclins, their regulators and their substrates in many human tumours has strongly stimulated the search for chemical inhibitors of CDKs. The potential use of these potent and selective kinase inhibitors in cancer therapy is presently under investigation. Recently a group from Glaxo Wellcome unexpectedly discovered a potential new application of these CDK inhibitors to prevent chemotherapy-induced alopecia. These cyto-protective properties might also be extended to other tissues damaged during chemotherapy.

Oral contraception, hormonal replacement therapy and hormonal therapy in cancer patients are commonly used in everyday practice. Venous and arterial thromboembolisms which are potentially fatal are among the most serious side effects experienced by women. In this review, we focus on the circulation, describing the hormonal alterations on hemostasis. The risk of thromboembolic event is discussed in relation with the different hormonal regimen. We will finally propose recommendations for oral contraception in presence of venous or cardiovascular risk factors.