Several cases of vasculitis have been reported in AIDS patients. They may occur as idiopathic disease or result from infection or cryoglobulinemia. In patients with Kaposi's syndrome, treated with bleomycin. Raynaud's phenomenon or digital necrosis can occur. The vascular toxicity of bleomycin is well known and does not seem to be more frequent in AIDS patients compared with other patients treated with this drug. The relation between eumulative dose of bleomycin and occurrence of peripheral vascular disease is undear.

Raynaud's syndromes may be observed in HIV-infected patients, particularly those with Kaposi disease treated with bleomycin. This complication occurs in 10% of patients given bleomycin although only 7 cases have been reported in the literature. The aim of this study was to determine the frequency of certain biological abnormalities observed in HIV patients with Kaposi disease given bleomycin and who develop Raynaud's syndromes.

Gemcitabine, a new nucleotide analogue, is a promising chemotherapeutic agent for pancreatic, lung, ovarian and breast carcinomas. Its low toxicity (mainly hematologic) makes it a good choice for palliative treatment in patients who would otherwise be unable to tolerate aggressive therapy. The combination of gemcitabine with other anticancer agents such as cisplatin and anthracyclines appears to be associated with high response rates. Finally, gemcitabine is a potent radiosensitizing agent and should definitely be tested in combination with radiotherapy mainly in locally advanced disease.

Cisplatin is one of the most widely used agents in cancer treatment. Cisplatin regimens can lead to a more or less pronounced hyponatremia in 4 to 10% of cases due to salt wasting with hypomagnesemia and normokaliemia. Functional and renal failure and orthostatic hypotension can be observed.

Amsacrine is an intercalating planar polycyclic aromatic molecule that displays antitumor activity. The cytotoxicity of this compound is related to its interaction with topoisomerase II. The substituent at position 1' on the aniline is thought to be essential to the formation of the topoisomerase II-DNA cleavable complex and hence the cytotoxicity of the drug. The influence of three substituents at position 1' on the modulation of the activity of topoisomerase II was investigated. The following observations emerge from our structure-activity relationship study: i) the effects of the drugs on topoisomerase II-mediated DNA cleavage in vitro are correlated with the results of the cytotoxicity assays performed with cells sensitive (DC-3F) and resistant to topoisomerase II inhibitors (DC-3F/9-OH-E); ii) depending on the nature of the 1' substituent of the drugs, the restoration of a normal topoisomerase II alpha catalytic activity in resistant DC-3F/9-OH-E cells transfected with a plasmid carrying a wild type topoisomerase II alpha cDNA (hTOP2) either does not modify the susceptibility of the cells to the drug or partially reverse the resistance phenotype. The molecular and cellular studies reveal that topoisomerase II alpha is implicated in the cytotoxicity of amsacrine and confirm that the substituent at position 1' on the anilino ring of amsacrine governs the interaction with topoisomerase II.

Specific epidemiologic data on myelodysplastic syndromes are rare. Analysis of data is in fact affected by problems of terminology and classification. The link between the exposure to ionizing radiation or alkylating agents and MDS is well established. Etiologic factors of acute leukemia, or new factors such as non ionizing radiation, solvent, ethylene oxide, glycol eters, tobacco smoke, exhaust gases, agricultural work have been hypothesized but should be confirmed by other studies on MDS.

Iatrogenic extravasations are characterized by their unpredictable course, the possible repercussions of functional, cosmetic and psychological sequelae, and the absence of a therapeutic consensus. The authors present the protocol used in Hôpital Saint-Louis, based on a synthesis of current procedures, consisting of emergency conservative surgical aspiration and lavage, performed in a context of close collaboration with oncolosits, intensive care physicians and radiologists. From 1994 to March 1997, fifteen patients were operated following extravasation during seven chemotherapeutic protocols, three radiographic examinations with injection of contrast agents and five resuscitation procedures. This simple protocol, applied systematically, achieved cure without cutaneous or functional sequelae in all patients. Aspiration-lavage during the first twelve hours therefore constitutes the treatment of choice of iatrogenic extravasation with cytotoxic or hyperosmolar aqueous solutions.

We report on a case of methotrexate (MTX) intoxication occurring in a 19-year-old man treated for a leukemia. Exchange-transfusion (ET) was performed in attempt to remove the MTX from the body. This exchange-transfusion was unable to decrease the MTX plasma concentration. This inefficacy of ET in MTX intoxication is in contradiction with previously reported recommendations. However, this result is easily explained by MTX pharmacokinetics parameters.

This multicentre randomized single-blind parallel group study compared the efficacy of oral ondansetron plus methylprednisolone (OND+MPS) with conventional antiemetic strategies (TH) over 4 consecutive courses in moderately emetogenic chemotherapy. This study was conducted in naive patients receiving a minimum of 3 cytotoxics including adriamycin (> or = 35 mg/m2) and cyclophosphamide (> or = 500 mg/m2) plus an other alkylating agent. Of the 364 patients included in the study, 70% had a breast cancer and 30% a lymphoma. Patients were divided into two groups. On day 1, one group of patients received OND (8 mg, po) 2 hours before chemotherapy, followed by a slow intravenous injection of MPS (120 mg) 30 minutes before chemotherapy. Eight hours after the start of chemotherapy, patients received OND (8 mg, po) and MPS (16 mg, po). On days 2-4, patients received OND (8 mg, po) and MPS (16 mg, po) twice daily. The second group of patients received conventional antiemetic treatment (benzamide plus corticosteroids with or without benzodiazepins). The primary efficacy parameter was defined as complete control of emesis (0 emetic episodes) over 4 consecutive courses of chemotherapy. In the OND+MPS group, 63% of patients experienced complete control of emesis versus 33% in the TH group (p < 0.001). The secondary parameters (percentage of days with no emetic episodes, control of emetic episodes, grade of nausea at each course, patient preference and quality of life evaluation) were always significantly better in the OND+MPS treated group. The percentage of days without any emetic episode over the 4 courses of chemotherapy was 91% in the OND+MPS group and 75% in the TH group (p < 0.001). Ninety-two percent of patients from OND+MPS group preferred to continue their treatment versus 76% in the TH group (p < 0.001). Concerning the quality of life assessed by FLIC and FLIE questionnaires, the analysis showed a significant difference at the end of the treatment in favor of OND+MPS (p = 0.037 and 0.0075 respectively). This study showed the interest in using the combination OND+MPS right from the first course of moderately emetogenic chemotherapy.

Advances in antimitotic treatments have improved the prognosis of cancer in young subjects. The resulting increase in life expectancy raises the question of the subject's future fertility, a question that should be posed before beginning any anticancer therapy which could lead to a gonadal failure. If oocyte donation remains the alternative indication proposed for these patients desiring a child, it is important to assess the tissue alterations in the uterus, to verify its vascularization under suitable treatment and appreciate the other alternative directions.

Studies of the relationships between the pharmacokinetics of a drug and its pharmacodynamics could significantly improve chemotherapy efficacy. However, despite their proven value, pharmacokinetic studies sometimes appear as cumbersome and difficult procedures. The bayesian approach associated with an optimal sampling time strategy (OST) allows the determination of the pharmacokinetic parameters of a drug with a smaller number of blood samples compared with that required by the classic maximum likelihood estimation (MLE). Therefore, the bayesian approach may lead to a less discomfort to the patients and less work for the medical staff. Such a method was developed to determine the individual pharmacokinetic parameters of etoposide (VP16). First, the statistical characteristics of the pharmacokinetic parameters were evaluated in 14 courses from 14 patients. Then, based on these results, a three-sample strategy was developed. Validation of this methodology was performed in 7 new patients and evaluated by computing bias and precision. The performance of the developed methodology shows that it could successfully be applied for the determination of VP16 pharmacokinetic parameters.

The aim of optimizing drug therapy for an individual patient is to maximize the likelihood of a desired therapeutic effect and to minimize the likelihood of toxicity. The excellent correlations between renal function and carboplatin total body clearance and between carboplatin area under the plasma concentration by time curve and thrombocytopenia allow calculation by Chatelut formula of carboplatin dosage.

Pharmacogenetics could be defined as the study of genetically controlled variations in drug response. Introduction of pharmacogenetics in hematology and oncology has been done recently. With recombinant DNA technology, like restriction analysis of genomic DNA, enzymatic amplification of DNA by the polymerase chain reaction and expression of cDNAs in cell cultures, this research area has been developed during the last 10 years. In hematology and oncology, we can integrate pharmacogenetics in 3 areas. First, the concept of genetic risk of cancer and the study of drug or carcinogen metabolizing enzymes that could modulate this risk, regarding the activity of some specific enzymes; second, the use of pharmacogenetics, related to the toxicity or efficacy of anticancer drugs, allowing the identification of key enzymes involved in the biotransformation of the drug and the study of molecular aspects involved in the regulation of the activity of the enzymes; third, the implication of the study of enzymatic activities in tumoral tissues as compared to non-tumoral tissues. The following differences between the 2 tissues can be subsequently used to increase the specificity of the anticancer drugs.

Increasing evidence implicates a critical role for aberrant Ras function in promoting the development of human tumours and has provided the impetus for identifying anti-Ras drugs for therapy. In order to be active the protooncogene ras must be associated with the plasma membrane. This feature depends crucially upon its farnesylation (addition of a 15 carbon moiety) by the enzyme farnesyl protein transferase. In the search for new anticancer strategies and agents, potent and selective inhibitors of this enzyme have been designed. The more recent of these compounds have produced impressive results in vivo against human tumours xenografted onto nude mice, without notable toxicity, making them promising candidates for clinical evaluation.