The growth fraction of cancer cells, estimated by the monoclonal antibody Ki-67 labelling, and DNA content were determined simultaneously en K562 human leukemic cells by flow cytometry. Adriamycin, aclacinomycin A and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreases the fraction of Ki-67 positive cells, Ki-67 negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

Doxifluridine, a new fluorouracil analog with a low myelosuppressive effect, has recently been subject to various disease-oriented, Phase II trials. For the present evaluation of drug tolerance, the Phase II data of 114 patients having received 376 doxifluridine cycles has been used. The treatment cycles consisted of 5 daily intravenous injections of 4,000 mg/m2 non-pretreated patients, and 3,000 mg/m2 in pretreated patients. Previous observations showing that doxifluridine is less myelotoxic than fluorouracil have been confirmed. 54% of the patients had no leucopenia (maintaining WBC counts over 3,000/mm3 and 90% had no thrombopenia (platelets not lower than 100,000/mm3) throughout treatment. However, a WHO grade 4 hematologic toxicity was observed in 9 patients, and 2 toxic deaths were related to severe granulocytopenia and sepsis. Digestive tract toxicity was similar and equally frequent as the one observed with fluorouracil: mucositis with oral ulcerations (19%), nausea and vomiting requiring specific treatment (8%) and severe but never hemorrhagic diarrhoea (5%). Neurologic toxicity was frequent, with 20% of patients complaining of somnolence and/or peripheral neuropathy, 7% of impaired consciousness and 1% of WHO grade 4 cerebellar ataxia. Among the 10% of patients with cardiac symptoms, 6% were benign and transient arrhythmias, and 4% were severe, including 1 myocardial infarction, 1 spontaneously reversible cardiac arrest and 2 ventricular fibrillations successfully treated with cardioversion. In spite of its encouraging antitumor activity and its good hematologic tolerance, intravenous doxifluridine, as used in this study, cannot be recommended because of the observed neurologic and cardiac toxicity. Oral doxifluridine is presently under investigation with preliminary results suggesting a lack of neuro- or cardiotoxicity.

This review reports on the various studies using fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR) to study the metabolism of antineoplastic or antifungal fluoropyrimidines. It is divided into 2 parts: the first examines ex vivo studies, ie, of biofluids or excised tissue samples from patients. In vivo studies, ie where the biotransformation of the drug is followed by non-invasively both in animals and in humans, are described in the second part. For ex vivo studies, 19F NMR can already be considered as complementary to the classical analytical methodologies used for drug metabolism studies. In vivo 19F NMR spectroscopic studies, especially in humans, are still at an early stage of development. Several improvements, both methodological (development of volume-selective localization techniques and quantification methods) and clinical (more rigorous definition of pathologies under study and administered treatments), are a prerequisite for useful clinical application.

A severe or lengthy disturbance of immunity favors the development of malignant tumors. The increased incidence of lymphomas, leukemias and certain carcinomas in cases of congenital immunodeficiency, as well as of Kaposi's sarcoma and certain lymphomas in the acquired immunodeficiency syndrome (AIDS) are well known. In transplantees, patients undergoing immunosuppressive treatment for autoimmune disorders and cancer patients receiving chemotherapy, the occurrence of secondary neoplasias represents a phenomenon with a specific profile. We have seen 14 solid tumors in patients who were immunosuppressed for one of the 3 above-mentioned reasons. It is a heterogeneous group, both in terms of patient profile and tumor localisation. However, there are certain characteristics of these tumors which distinguish them from similar ones arising in the general population. The advent of more aggressive immunosuppressive therapies, the constant increase in organ transplants and the development of new cancer treatment modalities which influence the patients immune systems explain the importance of this phenomenon. Thus one must constantly be wary of these unusual tumors which occur independently of age and usual risk factors.

Racemic 7-hydroxy-9-oxa-anthracyclinone (5a) has been synthetised in seven steps from quinizarin (6) and its resolution achieved after glycosylation with 3,4-di-O-acetyl-2-deoxy-L-fucose. Chiral pool syntheses of (8S)-8-hydroxymethyl-9-oxa-anthracyclinone (5b) and of (8S,10R) and (8S,10S)-8-hydroxymethyl-10-methyl-9-oxa-anthracyclinones (5c and 5d) have been achieved using (R)-2,3-O-isopropylideneglyceraldehyde (12) and leucoquinizarin (13) as starting materials. Glycosylation of aglycones 5b-5d by either 3,4-di-O-acetyl-2-deoxy-L-fucose or various 3-amino-2,3,6-trideoxy-L-hexoses yielded the corresponding anthracyclines. The synthetic glycosides do not show significant cytotoxic activity at a concentration of 1 microgram/ml against L 1210 cells.

The optimal approach to reduce bacterial infections in granulocytopenic patients is still controversial. Recently, fluoroquinolones have been developed and real progress has been achieved in the prevention of Gram negative bacilli septicemia. This study reports our experience with ciprofloxacin and shows the excellent tolerance of ciprofloxacin by our patients as well as promising data for the reduction of Gram negative bacilli infection. However, practical modalities to prevent infection caused by Gram positive cocci remain to be defined.

A 21-year old male patient with Philadelphia chromosome-positive chronic myeloid leukaemia received an autologous bone marrow transplant in consolidation of the 2nd chronic phase. The bone marrow had been treated with mafosfamide in adequate doses. The post-transplantation course of the disease was marked by an inversion: the duration of the 2nd chronic phase was more than 4 times longer than that of the first one, suggesting some degree of effectiveness of autologous bone marrow transplantation performed in the 2nd chronic phase and/for of the in vitro treatment of the bone marrow with mafosfamide. Cytogenetic monitoring was pursued throughout the course of leukaemia: regression of the Philadelphia chromosome was only partial and transient, and 3 clones appeared, each of them involving chromosome 1, for which mafosfamide was most probably responsible.

Peripheral neuropathy is a common manifestation of chemotherapeutic agents. Most drugs produce a distal axonal degeneration and long axons are predominantly affected, giving a clinical picture characterized by a symmetrical sensory neuropathy. The toxicity of therapeutic agents to the peripheral nervous system particularly includes those used in cancer-chemotherapy (cisplatin, vinca alkaloids), but antimicrobial agents such as isoniazide or nitrofurantoin and vitamin abuse (pyridoxine) are also discussed.

Over 8 1/2 years, we observed 27 patients with drug-induced respiratory disease (DIRD). The inducer drugs were mainly those used in cardiology (9 patients, of whom 8 had amiodarone pneumonitis), in oncology (8 patients), in rheumatology (4 patients; 3 from d-penicillamine and 1 from gold), and in neurology (4 cases from ergoline derivatives). The main pattern of DIRD was a diffuse interstitial lung disease having either a rapid, a slowly progressive or a chronic course. Only the two former patterns offered clearing following withdrawal of the drug. Severe bronchiolitis obliterans from d-penicillamine (2 cases) and pulmonary eosinophilia (2 cases) was also observed. The onset of DIRD occurred earlier, i.e. following shorter periods of drug administration (months), in the acute interstitial lung disease variant, while it occurred after years of drug exposure in subacute and chronic forms. In contrast to other reports, bronchoalveolar lavage lymphocytosis was not a prominent feature in amiodarone pneumonitis. The outcome was favourable in 16 patients; deaths was encountered during the florid phase of DIRD in 3; incapacitating sequelae were noted in 6 patients, leading to subsequent death in 2; the underlying disease accounted for 7 additional deaths. Therefore, DIRD are relatively common, develop often in patients with severe underlying conditions, and interstitial pneumonitis is their pattern of predilection. Amiodarone emerges as a common inducer, and accounted for more cases than all chemotherapeutic agents grouped together in our series.

This article details the pernicious odontostomatological effects provoked by antitumorous and immunosuppressive medication. The role of the dentist as a member of the chemotherapeutic team is highlighted as well.