Germinal cells are particularly sensitive to cancer chemotherapy in males. This toxicity is difficult to evaluate. It is the most frequently observed in young patients treated for curable cancers, by alkylants, specially if the treatment is intense and long. Depending on the patient and his age, on the cancer and its treatment, recovery of a normal spermatogenesis may be observed in a minority of cases and sometimes lately. This hazard must be told to the patient who is invited to preserve his sperm which is not always of enough good quality. There is no proved means to protect gonadal function. Therefore modifications of chemotherapy are desirable to decrease its toxicity.

Children with metabolic or toxic diseases affecting the brain stem were examined by MRI in an attempt to obtain images of brain stem systematization fibres and to determine their origin. A toxic cause may be envisaged in hazy, ill-systematized lesions, and a metabolic cause in well-systematized lesions.

The authors have studied a population of 51 children in which 63 central venous catheters were used for the treatment of leukemias, solid tumors and lymphomas. Two groups were isolated: continuous hospitalization (group A) and intermittent hospitalization with periodical day care (group B). Mean duration of catheterization was 129 days in group A and 176 days in group B (whole population: 149 days), with a total of 9,724 days of catheterization. There was no significant differences between the two groups concerning infection, bleeding, thrombosis or migration. So the authors believe that permanent hospitalization is not mandatory for chemotherapy in children with severe malignant diseases. Periodical day care therapy allows a near normal life for children and a better cooperation from their parents.

The lack of decisive progress in ovarian cancer chemotherapy in recent years led the ARTAC "Ovary" group to initiate a study based on the hypothesis of collateral sensitivities. In this phase I-II trial, NHO-88, the V-H combination (associating vinorelbine (VNB) and hexamethylmelamine (HMM) was studied in patients with advanced ovarian adenocarcinomas, most of which had become resistant to previous chemotherapy. The aim of the study was to find an active combination without complete cross resistance with first-line platinum salt based combinations, such as CAP, FAP or CACb-300. A pilot feasibility study was first carried out to determine the maximum tolerated weekly dose (MTWD) of VNB (20 mg/m2/week), HMM being administered per os on days 1-14 of every 28-day cycle at a standard dose of 250 mg/m2/day. An open phase II-A study was further carried out according to a 2-step sequential analysis method for phase II clinical trials. We observed: 1), a good tolerance of the V-H combination apart from frequent neutropenia; 2), a response rate of 35% (95% confidence interval: 23-47%); 3), a median response duration of 4 months (range: 1-7 months); 4), in some cases, the absence of a complete cross-resistance between the V-H regimen and the previously administered platinum-based combinations. These results, which are currently being validated (phase II-B ongoing), constitute the first step in the search for active systems of sequential or alternate chemotherapeutic regimens for the treatment of advanced carcinomas.

In experimental models chemotherapeutic agents enhance spontaneous metastases. Vascular toxicity and myelotoxicity may account for this phenomenon. However, drugs may act directly on tumor cells. Clonogenic resistant cells are involved in the metastatic process facilitation. Fundamental biological mechanisms are evoked to explain these observations. Mutagenicity and its consequences on gene expression or regulation are another hypothesis. Clinical investigations are necessary to confirm the results obtained from animal models.

Concentrations of estrogen receptors, progesterone receptors, unconjugated estrogens (estradiol and estrone) and sulfate-conjugated estrogens (estradiol sulfate and estrone sulfate) were determined in patients treated with Decapeptyl and in controls. After prolonged Decapeptyl therapy, a highly significant fall in progesterone receptors was evidenced; estrogen receptors were found to be decreased in the myoma as compared with the secretory phase in controls and in the myometrium as compared with the proliferative phase in controls. Tissue levels of estrone sulfate and estradiol sulfate decreased very substantially. In conclusion, Decapeptyl emerges as a very promising agent for the treatment of uterine myomas.

A prospective study of mandibular alveolar bone resorption has been achieved on 49 patients with upper aerodigestive tract tumor and treated by radiation therapy and/or a chemotherapy, on 30 patients who were not treated. All these patients were subjected to dental extractions followed by X rays in coronal and sagittal view, during at least one year, at the rate of one X ray every three months. The comparative study enabled to show a quite similar resorption for the two population, a slightly more important resorption on incisor and canine regions, and a stopping of the resorption about five months later according to dental extractions. Radiation therapy and chemotherapy (therapeutic doses) may not have significant influence on alveolar bone resorption after dental extractions.

Treatments given for childhood malignancies can alter gonadal function by several mechanisms: (1) cranial irradiation may cause either gonadotrophin deficiency or premature puberty. (2) Irradiation of the testes can induce germinal epithelium dysfunction even if the dose delivered is very low; Leydig cell failure occurs beyond 5-6 Gy and ovarian insufficiency beyond 6-7 Gy. (3) Chemotherapy is considerably more toxic for the germinal epithelium of the testes than for the ovaries; alkylating agents are especially toxic. Analysis of the consequences of preparation for bone marrow transplantation by chemotherapy or total body irradiation will be required when longer follow-up are available.

The present recovery rate of brain tumors (20% of solid tumors in children) is 50%. Besides the progress made in neurosurgery and radiotherapy, those of chemotherapy have indisputably had an impact on the improvement of the rate of recovery. Protocols in use differ according to the histologic type of the tumor (astrocytoma, glioma, medulloblastoma). Indications for therapeutic trials for phase II and III tumors will require a longer period of follow-up as well as strict analysis of the result.