Hyperplasia of the thymus, an uncommon development following chemotherapy, raises doubt concerning possible tumor recurrence. We report a case of thymic hyperplasia in a 12-year-old girl who was given chemotherapy for a cervicomediastinal lymphoma. Three months after treatment end, dry cough and an enlargered mediastinum suggested recurrence, but histological examination of tissue biopsy demonstrated benign reactive hyperplasia. Outcome was favorable without recurrence after corticosteroid therapy. According to the literature, thymic hyperplasia is neither tumor nor treatment specific. It generally occurs in children but may be observed in young adults. Hyperplasia of the thymus following chemotherapy would appear to be a good prognosis factor.

Is it possible to give a hormonal replacement therapy to a post-menopausal woman with a past history of breast cancer? As estrogens exert a proliferative effect on mammary cells, it remains a controversial issue. Only few studies have been conducted, generally uncontrolled, and involving only a small number of women given short-duration treatment. The endocrinologic arguments are discussed here. Hormone replacement therapy must be replaced in a general discussion on the potential risks for the breast and uterus, and the beneficial effect on coronary heart disease, osteoporosis, and quality of life. The risks and benefits must be weighted for each woman. The circumstances of prescription of hormone replacement therapy, and of the antiestrogen tamoxifen, which has proven a beneficial effect as adjuvant therapy for the menopausal women with a early breast cancer, must be discussed. Some physicians propose a prospective clinical trial to give an answer. Another way could be improvement of our knowledge about the prognostic factors of breast cancer, and better identification of possible "hormonal independance".

Taxoids (paclitaxel, Taxol and docetaxel, Taxotere), drugs which stabilize microtubules, demonstrate marked activity against ovarian, brain and lung cancer. We investigated, on the human colon adenocarcinoma HT29-D4 cell line, firstly the effects of taxoids in function of the differentiation state and secondly the effects of a low dose of paclitaxel on the differentiation process. The cellular parameters studied were microtubular network, cell cycle and cell tubulin content. Undifferentiated cells treated with paclitaxel or docetaxel (10-100 nM) classically induced bundles in interphasic cells and pseudoasters in mitotic cells, arrest in cell cycle in G2M and increase in tubulin content. Inversely, no modification was observed in differentiated cells after similar taxoid treatment. Long-term low-dose pretreatment of differentiated cells restitutes some sensitivity to taxoids since these cells become responsive to further taxoid treatment, as reflected by modifications of the microtubule network.

Delirium is a complication related with the treatment and the evolution of cancer diseases. This disorder occurs more often among patients who are under treatment (chemo or radiotherapy) and among those who are terminally ill. Estimates of prevalence of delirium range from 4% to 40%. Delirium must be detected and treated as soon as possible because it is often associated with a poor prognosis of the cancer disease and with the development of an important distress of patients and their relatives. Delirium may have several underlying causes. Management of delirium has to be symptomatic and etiological, including support of the family. Education of the caregivers, for a better detection, treatment and control of these disorders, should be more systematic in order to improve the quality of the care given to patients with cancer. The present work reviews literature concerning these different aspects.

A fall in the PSA level after stopping antiandrogens has been described at the stage of hormonal escape of prostatic cancer treated by complete androgen inhibition. The authors report a new case. The patient was offtially treated by pulpectomy and nitulamide for N+ prostatic carcinoma (PSA: 165 ng/ml). At the stage of hormonal escape, discontinuation of nitulamide induced a reduction of the PSA. Replacement of nitulamide by cytoproterone acetate was followed by a renewed increase of PSA, which again decreased after stomming cyproterone acetate. Three years later, the PSDA level was 3.5 ng/mg. This syndrome is probably due to mutation of the androgen receptor. In hormonal escape, suspension of all antiandrogens apart from LHRH analogues is recommended and can be followed by a temporary fall of PSA. No other antiandrogen must be administered in the place of the previous drug.

Despite good general and hematological tolerance, hydroxyurea frequently causes polymorphous skin lesions when given as long-term therapy. Distal skin atrophy, pseudodermatomyositis, pseudolichen and ulcerations have been observed.

The aim of this study was to test topical applications of dimethylsulfoxide and alpha-tocopherol for the prevention of ulcerations after antimitotic extravasation.

We report one case of hepatic encephalopathy following the administration of a somatostatin analogue (lanreotide) in a patient with a pancreatic endocrine tumor and liver metastases. Hepatic insufficiency was absent. The diagnosis of hepatic encephalopathy relied upon a positive re-challenge test, elevated veinous ammonemia, suggestive findings on electroencephalogram and lack of recurrence after lanreotide discontinuation. Encephalopathy was thought to be due to a significant decrease in hepatic blood flow caused by lanreotide; an associated thrombosis of the portal vein may have played a facilitating role.

A 72-year-old male treated with flutamide for metastatic prostate cancer developed lethargy and confusion. He was noted to be icteric and his liver enzymes were elevated. Within a week of discontinuing the medication, the patient's mental status and liver function returned to normal. Although flutamide-induced near fatal liver dysfunction has been described, progression to encephalopathy is a rare occurrence. Based on a review of the literature, management guidelines for the use of flutamide are suggested.

Central venous catheters have considerably improved the comfort and safety of chemotherapy in cancer patients. However complications as thrombosis could occur and their incidence vary from 3.7 to 42% in oncology. Catheter placement induces modifications of vascular system with formation of a fibrin sleeve and/or a mural thrombus. Thrombosis origin is linked with catheter itself, its position and the biomaterial used. Hypercoagulable state in cancer results from the perturbation of blood flow, the composition of blood itself and the vessel wall, and increases the iatrogenic effects of indwelling catheters. Finally chemotherapy used in the treatment of cancer has been associated with an increased incidence of thromboembolic events, suggesting the proposal of an antithrombotic prophylaxis in cancer patients receiving chemotherapeutic agents through indwelling catheter.

The authors show the responsibility of antimitotic chemotherapy on the disturbances in dental development in the young children. They insist on doing an odonto-stomatologic check-up at the beginning of the treatment and to keep a constant watch during the treatment and until the end of dental evolution.

In this work, the authors have used technics of multivariate analysis to determine the structure-activity relationships of 46 podophyllotoxin derivatives and analogs studied for their antineoplastic and antiviral activities. The obtained results allow to envisage the possible synthesis of more specific molecules by making modifications in the structure of the model molecular archetype.

Anticancer drugs dosage are currently adjusted to body surface area. This measure is supposed to be the best morphometric parameter to adjust anticancer drug doses. However, dose adjustment to body surface area has not historically been rigorously demonstrated. We propose a method to objectively test this parameter utility. The statistical justification of drug adjustment to body surface area can use mathematical equations to be expressed. We can demonstrate that body surface area and plasmatic total clearance of a drug should be correlated to adjust dose anticancer drug to body surface area. When we test the hypothesis of body surface area and plasmatic clearance correlation for cytarabine and adriamycin we did not find any significant correlation. For these anticancer drugs, dose adjustment to body surface area increase their pharmacokinetic and efficiency variabilities. The concept of dose-intensity is probably the best justification of individual dose adjustment from plasmatic drug samples, and from pharmacokinetic and pharmacodynamic studies. The determination of the "maximal tolerable exposition" and of the "minimal effective exposition" should reduce the overexpression of toxic risks and avoid the ineffective underexpositions. However, it is difficult to precisely define these two expositions and to research the most relevant pharmacokinetic parameters to their measure. Area under curve appears to be their most appropriate expression.

Since its discovery in 1948 the clinical applications of methotrexate have widened; and in order to overcome resistances to methotrexate, the concept of high-dose methotrexate has been proposed. The use of rescue by folinic acid, as well as rapid dosage of MTX coupled with pharmacokinetic studies, have permitted us to administer an optimum dose of drug, with maximum therapeutic effects, but with reduced toxicity. Individual adaptation of posology, calculated using the test dose or according to population pharmacokinetic with a Bayesian method of parameter estimation (which allows us to adjust the dose of high-dose methotrexate during its infusion) permits control of inter and intra-individual variations of this drug. After analysis of the different methods proposed, we now present the results of 778 courses of treatment by high-dose methotrexate (while separating 238 courses for osteosarcoma as these formed a homogeneous group of patients). Theoretical maximum concentration and length of infusion were decided by physicians, followed by individual adaptation of posology by pharmacologists at the sixth hour of infusion of methotrexate. This treatment unites maximum security for the patient with no serious side effects (no grade 4 toxicity according to WHO classification), while receiving an optimum dose of methotrexate. In courses of MTX for osteosarcoma, the dose of MTX can be further intensified without risk, by administering on average 65% more than the usual dose in adults (8 g/m2) and 10% more than the usual dose in children (12 g/m2).