The use of carboplatin has become frequent in children solid tumours because of lower renal and otologic risks as compared to cisplatin. The efficacy of carboplatin has mainly been demonstrated when used in combination with other cytotoxic drugs: few phase II studies of carboplatin alone have been published in children. Because of its limiting haematologic toxicity, carboplatin has become the main platinum compound when used at high dose with hematopoietic stem cell rescue. Formula have been developed specifically in children to allow a determination of the prescribed dose using a targeted "area under the curve" rather than dose in mg/m2, which allows a better individual therapeutic adaptation. Long term follow-up after carboplatin treatment in childhood is mandatory mainly because of the mutagenic and hypofecondity potential risks.

Carboplatin differs from cisplatin by its pharmacokinetics and toxicity profile. Carboplatin is mainly eliminated by the kidneys and its dose-limiting toxicity is the bone marrow suppression. Myelosuppression of carboplatin is more closely correlated with the area under the curve (AUC) of ultrafiltrable plasma concentration versus time to which a patient is exposed, than it is with the administered dose. Similar relationships have been shown between AUC and antitumour effect, although they are in a smaller number and less close. Several methods of dosage individualisation a priori (before carboplatin administration) have been proposed. Since carboplatin is often prescribed to patients with altered renal functions, this dose optimisation is particularly justified. Dose individualisation is based on both equations allowing to predict the patient carboplatin clearance and the choice of target AUC. The different equations proposed are based on direct measurement of the renal filtration glomerular rate or on patient demographic and biological characteristics such as weight and serum creatinine. The respective advantages and limits of these equations are now well known. However, the values of optimal AUC that depend on cytotoxic drugs combined to carboplatin and the patient hematopoietic status, are not precisely determined for each protocol of chemotherapy. When carboplatin is given by reiterated administrations within each course, it is possible to adjust the last doses according to a limited number of blood samples following the first infusion and a Bayesian analysis of the observed plasma concentrations. These methodologies are more complex, but they may be useful for the intensification protocols. Carboplatin is still the only cytotoxic drug for which dose is individualised not according to the body surface area but according to pharmacokinetic parameters.

Platinum compounds primarily act by damaging cellular targets inducing direct or indirect DNA alterations, and cytoplasmic proteins modifications. Molecular and cellular mechanisms of platinum resistance include increase of DNA repair, amplification of detoxifying proteins, modification of platinum transport, and alteration of oncogenes expression. This overview will describe those preclinical constatations related to cisplatin and will focus on carboplatin specificity.

Two axes of research have been explored, one about promising non-acidic non-steroidal anti-inflammatory derivatives, with indolin-2-one as structural core and another one about aromatase inhibitors, characterized by azolylmethyl or alpha-azolylbenzyl chain on indole nucleus. Knoevenagel reaction led to indolin-2-ones substituted by either 2,6-di-tert-butylphenol chain or 1, 4-dihydropyridine chain, revealing antioxydant or anti-inflammatory activities. Aromatase is a logical target in the treatment of hormono-dependent breast cancer in postmenopausal women. Among non steroidal inhibitors of this enzyme, diverse compounds with anilino or azaheterocyclic moiety are currently used or undergoing clinical trials. Our pharmacomodulation in azolylmethylindole or alpha-azolylbenzylindole series led to compounds with high level aromatase inhibitory activity. Work to determine their selectivity by measuring their inhibitory effect on P450 17alpha enzyme was also carried out. A first molecular modeling approach with Discover software was performed to evaluate interactions between our molecules and the catalytic site of P450cam.

Cutaneous necrosis occurring in the course of treatment by alpha interferon is an uncommon side-effect. Its physiopathologic mechanism remains obscure. A local thrombotic action of interferon has been suggested to explain its occurrence.

Alpha, beta or gamma interferon (INF) are cytokines produced by cells in response to antigenic stimulation. They are used to treat various hepatic, hematological, oncological and neurological diseases. Cutaneous reactions (rash, alopecia, labial herpes, erythema, or induration at the site of injection, and more rarely cutaneous necrosis) represent 5 to 12% of side-effects observed in patients receiving INF. The authors report six cases of local cutaneous reactions to alpha INF, five of which corresponded to cutaneous necrosis. This makes them question the relevance of INF reintroduction.

Anticancer drugs rarely cause strokes. We report the case of a woman treated for a kidney cancer by IL2 and IFN alpha, having developed multiple strokes associated with a livedo. The responsibility of IL2 and IFN alpha seemed likely. The association with a transitory livedo suggested that the pathological process might be a cerebral angiopathy with arterial vasospasms.

Very high concentrations of cytotoxic drug may be obtained with chemotherapy performed with vascular exclusion.

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.

This review on psychological consequences of chemotherapies presents the research directions developed during the last two years: the first direction is a descriptive one and identifies the prevalence of psychological syndromes associated with these treatments. Besides psychological distress such as anxiety and depression, often underestimated in medical practice, some secondary cognitive deficiencies ought to be considered. It is also emphasized that the point of view of patients should be taken into account since their own assessment of the side effects is often discrepant with those of their medical providers. The second orientation developed here is the evaluation of actions aimed at controlling and alleviating the psychological consequences of these treatments by different protocols of information and psychotherapy. Good quality research is necessary in psycho-oncology in France and should be co-ordinated with clinical practice in psychology the offer of which is still too limited in our present health care system.

The purpose of this study was to determine whether a systematic strategy of multiple microbiological samples for all adult patients with neutropenia admitted to an intensive care unit could document sepsis despite prior empiric antibiotic therapy.

Recent data have shown that the in vitro and in vivo cytotoxicity of bioreductive drugs could be significantly increased by combination with ionising radiation or chemotherapy. Various parameters such as oxygen tension and timing of administration of the drugs could play a crucial role in the efficacy of combined treatment modalities. The aim of this study was to define the oxygen dependency of cell survival after in vitro irradiation and incubation with tirapazamine, a bioreductive drug, and cisplatin given alone or simultaneously. Two human cell lines were studied: one cell line sensitive to tirapazamine, Na11+, a pigmented melanoma with a high percentage of hypoxic cells, and a less sensitive cell line to tirapazamine, HRT18, a rectal adenocarcinoma. Gas changes were made to study cell survival at four different oxygen concentrations (pO2): air (20.9% O2), 10.2 and 0.2% O2. Cells were incubated with tirapazamine and cisplatin alone or combined for one hour at 37 degrees C, then irradiated and cultured. For Na11+, cell survival after irradiation was comparable in air and at 10% oxygen with the two drugs given alone or combined. At 2 and 0.2% oxygen, cell killing was largely increased by tirapazamine and was not modified by the addition of cisplatin. For HRT18, cell survival was not modified when cisplatin was added to radiation, whatever the oxygen partial pressure. At low pO2 (2 and 0.2%) the cytotoxic effect of tirapazamine was not significantly decreased by the addition of cisplatin. When cytotoxic and bioreductive drugs are combined to radiation, the magnitude of the observed effect is highly dependent on the partial oxygen pressure and on the sensitivity of the cell line to the individual drugs. This has very important implications for clinical strategies based on combined chemo-radiotherapy.