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After an increase in the 1980s, incidence and mortality for prostate cancer in North America or England and Wales started to decrease in the early 1990s. The reasons for this evolution are widely debated, notably the importance of early detection. This study describes trends of prostate cancer incidence and mortality in 5 areas in France, where practices of early detection for this cancer are widely used. The 5 French administrative areas, covered by a population-based registry, have a total population of approximately 1,700,000 men. Incidence data from these registries were studied for the period 1982-1995, and mortality data were provided by the Institut National de la Santé et de la Recherche Médicale (INSERM) for the period 1982-1996. Age-Period-Cohort models by Poisson regression were created to characterize these trends. Between 1982 and 1995, 14,699 cases of prostate cancer were registered by the 5 registries under consideration. After a little intensification of the increase in 1987, undoubtedly due to early detection (notably using Prostate-Specific Antigen), the trend of the incidence seems to reverse from 1993. Mortality increased monotonically from 1982-1990 by an average of 1.8% per year, before decreasing annually by an average of 3.3% until 1996. Poisson regressions indicated a period effect on both incidence and mortality data; a small, but significant, cohort effect exists for incidence evolution, showing that elements such as etiologic factors may have an influence. Until results of randomized studies on mass screening are available, the question of individual screening remains; improved knowledge of risk factors could be interesting.

This multicentre, randomized double-blind study was undertaken to assess the efficacy of corticosteroids as a palliative treatment of intestinal obstruction due to advanced and incurable cancer. Thirty-one French palliative care units agreed to participate in the study and 12 actually recruited at least one patient. To be included, patients had to have an advanced cancer with a surgically inoperable bowel obstruction and to have received no specific anticancer therapy within the preceding 28 days. They had to fulfil at least three of the following criteria: vomiting at least twice a day; colicky abdominal pain; no flatus for 12 h or more; no stool for at least 4 days, faecal impaction being excluded; intestinal distension; air–fluid levels or absence of gas in the colon on an abdominal radiograph. Patients were randomized in three groups to receive either a placebo for 3 days (group A), or methylprednisolone 240 mg daily for 3 days (group B) or methylprednisolone 40 mg daily for 3 days (group C). Symptoms were assessed daily but success or failure of the treatment was assessed on day 4, according to the disappearance or persistence of symptoms. Fifty-eight patients were randomized, of whom 52 were able to be evaluated. Details of symptoms and associated treatments are described below. Of 40 patients without a nasogastric tube, symptoms were relieved in 68% of cases versus 33% among placebo-treated patients (P = 0.047). In 12 patients who had a nasogastric tube already in place, the results are less significant (60% versus 33% with P = 0.080). Because of the small sample size, no conclusions can be reached about the relative efficacy of low versus high-dose treatment regimes.

We investigated four mechanisms of intrinsic chemoresistance in a series of 67 human brain tumours including 31 gliomas (one grade I ganglioglioma, nine grade II and 10 grade III astrocytomas, 11 glioblastomas), 13 cerebral metastases, one medulloblastoma, one malignant teratoma, three ependymomas and 18 meningiomas. We studied four genes by northern blotting: multidrug-resistance (MDR 1), glutathione-s transferase (GST pi), dihydrofolate reductase (DHFR), and topoisomerase II (Topo II). The Topo II gene was absent in the normal adult brain (100%) and in 64% of the tumour samples tested. A second gene, GST pi, was found to be overexpressed in 38% of brain tumours. The two other chemoresistance-related genes were occasionally overexpressed in brain tumours (2% for MDR1, 9% for DHFR). Our results provide evidence that chemoresistance is intrinsic to the brain tissue and seems likely to be a multifactorial process.

The end-point of this survey was to evaluate the number of patients in advanced or terminal phase of a life-threatening disease and hospitalised in the university hospital in Grenoble on a given day. The secondary end-points were determination of the profile of patients undergoing palliative care and the therapeutic charge they represented for the hospital in order to develop optimal medico-psycho-social responses adapted to the needs of this population, their family and friends and the teams of health professionals who treat them.The survey was based on a questionnaire including 106 items and one open question, filled-in by a physician and the nurses of the hospital, together with the interviewer.Out of the 1495 patients hospitalised in the hospital centre (84% occupation), 114 patients were included in the study, i.e., 8% of the total number of patients present. Patients' mean age was of 70 (21x98); 40% were aged over 75. The principle motivation for hospitalisation was an acute medical problem (54%) followed by the impossibility of remaining at home (42%); 32% of the patients were hospitalised for a scheduled follow-up or treatment. The pathologies most frequently observed were cancer (61%) and neuro-degenerative disorders (28%). In our study, this category of patient exhibited a complex and heavy medico-psycho-social profile. It also revealed, when compared with a similar study conducted in 1996 at the Pitié-Salpêtrière hospital, that the identification of an advanced or terminal phase of a disease was generally late and probably prohibited the patients, their families and the nursing staff from access to specific accompaniment.Our results demonstrate the need for palliative care unit (with beds) in large establishments such as the university hospital in Grenoble, in the centre of large towns. Although not all terminally ill patients require a specialised palliative care unit, we feel that the creation of such units will be mandatory in the years to come, if only because of public pressure or necessity.

With SWICS and SEPICA onboard ACE, ionic charge measurements are now available for a wide energy range, covering the solar wind and suprathermal energetic particles. The high sensitivity of SEPICA has been utilized to examine the heavy ion composition and mean Fe ionic charge state as a function of time for several large, gradual, CME related solar energetic particle events. We selected those events for further analysis that clearly show small Fe/O ratios and low mean Fe ionic charge states (QFe∼10–12) throughout the event, excluding by this method a possible admixture from impulsive events. We determine for these events with SEPICA the mean ionic charge states of C, O, and Fe in the energy range ∼0.2–0.6 MeV/nuc and with SWICS the ionic charge distribution of C, O, and Fe ions of the solar wind. We find for this sample of ‘pure’ gradual events for suprathermal ions consistently low mean ionic charge states of ∼5.5 (C), ∼6.7 (O), and ∼11–12 (Fe). We compare the suprathermal charge states with solar wind m...

Caring for cancer patients is expensive, warranting verification that health care organization works in a satisfactory way. A first step of this evaluation deals with the description of the pathway followed in the health care system by the patient.671 breast cancer cases were diagnosed in Isère in 1995. According to the place where each treatment (surgery, chemotherapy, radiotherapy) was performed, we described pathways for the patient, either entirely private, public or mixed. Characteristics of the patient (age, place of residence), of the disease (extent of disease, way of discovery) and of the physician (general practitioner, specialist) might have influenced the choice of this pathway. We described and tested the distribution of these characteristics within the 3 groups using univariate analysis. Relative risk of being affected to the private pathway compared to the public one was computed, after adjusting for age, type of physician, extent of disease, way of discovery and sanitary area, using a multivariate analysis (logistic regression).In the department of Isère, the private pathway cared for 55% of breast cancers, the public one 23% and the mixed one 19%. There was no preferential recruitment according to age, physician type, presence of metastasis or of the rural or urban residence. In sanitary area number 5, characterized by an important attraction of the patients by the nearby department of Rhône, 41% of the patients were cared for the private pathway, compared to 63% in sanitary area 4, where most patients were treated in the main town of Isère: Grenoble. After early breast cancer detection with mammography instead of breast cancer screening, probability of being cared for in the private pathway was 2-fold higher (OR = 2) than in the public one.In Isère department, early breast cancer detection with mammography is in favor of the private pathway. This is not true for physician type, neither for characteristics of the patient or extent of the disease. Finally, the distance to next department of oncology or radiotherapy plays a major role.

Our responsibility toward others is the domain of ethics. To care particularly of a terminally ill patient, makes the relation asymmetrical. More, the doctor is exposed to unconscious trends like projections, desire of power, and anticipated grief of his/her patient. When warned against these psychological issues, the doctor will have at his/her disposal ethical landmarks that have been internationally accepted: principles such as autonomy and humanity of the patient, proportionality and futility, refusal of euthanasia and the principle of justice in palliative care. In front of the reality of a terminal patient care these principles enable the doctor to discuss the issue of disclosing a lethal prognosis. Stopping unproportionate treatments enables the doctor to avoid overtreatment. If a team consensus is helpful for a decision making, it does not exempt the doctor from his/her responsibility. The principle of beneficence makes for the doctor a duty to get educated and trained in palliative care with both their therapeutic and relational aspects. Lastly, a demand of euthanasia is a call for help; it justifies--instead of an act which must be refused--an unconditional listening and a commitment to do everything able to yield relief.

Immunoscintigraphy using indium-111-labeled OC125 monoclonal antibody F(ab')2 fragments is a technic complementary of morphological imaging (i.e. ultrasonography and computed tomography). It allows early detection of recurrences of ovarian carcinomas. We performed immunoscintigraphy 30 times in 26 patients who previously underwent radical treatment for ovarian carcinoma, and were suspected to have a recurrence. Our purposes were appreciation of diagnostic accuracy of the method, and above all its impact on clinical decisions and evolution of the patients. There were, after reevaluation of the results, 18 true positives, 7 true negatives, 3 false negatives and 2 false positive cases (sensitivity 85.7%, specificity 77.8%). Bayesian analysis showed positive and negative predictive values of 86% and 87% when probability of recurrence a priori was 50%, and 80% and 58% when probability of recurrence a priori was 70%. The result of immunoscintigraphy contributed to clinical decisions in 24 cases out of 30, and led to a correct decision for the patient in 21 cases. Conversely, for the 6 cases in which the result has not been considered, to take this result into account would have been beneficial in 4 cases, but harmful in 2. Finally, survival tended to be longer when immunoscintigraphy was negative, which could be associated with a better prognosis. We conclude that OC125-immunoscintigraphy may be useful for ovarian carcinoma follow-up and may contribute to a better therapeutic strategy.

Two thousand lung cancer patients were registered as Grenoble's university hospital joint oncology clinic from 1/1/1982 to 12/31/1991. These cases consisted of 449 small cell lung cancers (SCLC) and 1,551 non-small cell lung cancers (NSCLC). SCLC patients had a 4.6% and 2.9% survival rate at 5 and 10 years and only 7.2% of patients had a survival longer than 30 months. The main prognostic factors for survival were age, sex, TNM stage and WHO performance status. There was no increase in survival during the 2 periods of the study. NSCLC patients had a 14% and 7% survival rate at 5 and 10 years. Among 727 stage III or IV patients not treated with surgery, 2% were alive at 30 months. The main prognostic factors for survival were age, histology, TNM stage and WHO performance status. There was no increase in survival during the 2 periods of the study.

Prevalence of malignant neoplasm is a basic health indicator used in order to evaluate needs in medical equipment for treatment and follow-up of cancer patients. Data on prevalence are regularly published by Northern European countries. Thames and Connecticut cancer registries. In France available information on prevalence are scanty, because follow-up of cancer patients is not easy. Therefore, we used a statistical method to evaluate prevalence from incidence and mortality in the Rhône-Alpes area (France, 5,300,000 inhabitants) in 1990, using the department of Isère population based registry. For females, figures for breast carcinoma and colorectal carcinoma are respectively 25,000 and 5,700, and, for males, 5,700 colorectal carcinoma. For 5 year partial prevalence, these figures are respectively 11,300, 3,100 and 3,500. The ratio prevalence/incidence is 8.9 for breast in females, 5.8 for colorectal carcinoma in females and 4.8 for colorectal carcinoma in males with a steep decrease for 5 year partial prevalence (4 for breast carcinoma, 3.1 for females colorectal carcinoma and 2.9 for males colorectal carcinoma). These ratios are consistent with those observed elsewhere in Europe.

Between 1979 and 1990, the incidence rate (World Standard) for cancer of the prostate in the region of Isère (France) increased from 22.1 to 45.0 cases per 100,000 men, although there was no concurrent increase in mortality (16.0 to 17.6 cases per 100,000 men). This represents a mean increase per year of 6.3% for incidence, compared with 1.3% (NS) for mortality. Incidence of cases with metastases at diagnosis also remained stable with time. In this area, Prostatic Specific Antigen assays began in 1987, and rectal ultrasonography was implemented in 1984, but activity peaked only in 1988. Thus, during 1986-1988, there was both an implementation of new diagnostic procedures and an increase in the incidence of prostatic carcinoma, which suggests that the latter was the result of increased detection of small latent carcinomas. This has implications for public health since apart from increasing costs, it might unduly disturb the life of otherwise healthy people.

Desmoplastic tumours with divergent differentiation are principally located in the abdomen and develop locally or regionally. They occur in adolescents or young adults and are characterized at histology by a proliferation of undifferentiated small cells surrounded by a dense stroma. Only immuno-histo-chemistry provides the diagnosis. Since their chemosensitivity is rare and often partial the outcome is usually lethal. Six new cases of this recently described entity are presented here. The authors are in favour of a multidisciplinary and aggressive management, combining intensive polychemotherapy, extensive surgical exerisis and total abdominal radiotherapy.

A high excess of risk (standardized incidence ratio S.I.R.: 320 [190-490]) of intracranial tumors among men living within the county of Meylan, in the suburb area of Grenoble, as compared with the overall population was shown by the Isère Cancer Registry, for the period 1979-1984. There has been no change of this excess of risk between 1979 and 1990 (S.I.R. = 190). The pathological homogeneity of this cluster (neuroglial tumors) among men is noticeable. This county is known as a concentration of high-tech and intellectual professional activities. A descriptive study was conducted on the 24 cases diagnosed between 1979 and 1990, based on retrospective interviews of patient's family. Ethnical origins, blood groups, personal and familial medical history (with special interest in cranial injuries), socio economic status, chemicals, radiations and electro-magnetic exposures, acoustic and visual exposures (such as noises and T.V.), drinking water, tobacco and food consumptions, were investigated. Educational level, occupation, and European ethnic origin are all pointing to the same direction: a higher risk in high level social classes and high level professions. An analytical study is going on, that would give a deeper insight in these phenomenons.

Systematical registration of morbidity for lung carcinoma of the primary type was performed since January 1979 for the department of Isere, where a population of 940,000 inhabitants are living. Results for nine years registration (1979-1987) are dealing with 2,590 new cases. Crude incidence for primary lung carcinoma is 55.7 per 100,000 among men, and 5.9 for women (sex ratio: 11.7). Upper lobe is the site more concerned. There is no preference as regard laterality. When lymphatic nodes are explored (32%), there is an extension of the carcinoma for 75.2% of them. At the moment of the diagnostic, there is already a metastasis for 24% of the patients, mainly for bones. Among men and women, proportions for the squamous cell type are respectively 52.6% and 22.3% (60.8% and 28.7% of histologically identified cases), for the small cell type: 18.4% and 16.3% (21.2% and 21.0% of histologically identified cases), and for glandular carcinomas: 13.2% and 32.1% (11.9% and 41.5% of histologically identified cases). Results of the pathological examination are known in 92.8% for primary lung carcinoma cases. As regard first course treatment, surgery is performed in 34.9% of the cases, radiotherapy in 60.4%, and chemotherapy in 32.2%. Fairly high incidence of lung carcinoma in man in Isere, contrasts with rather low incidence in woman, a situation rather different that the one in England and North America, where figures for women are slowly gaining over the one's for men.

In this retrospective study, 91 patients (30%) out of a series of 304 with metastatic cancer of unknown primary site were found to have liver metastases. The liver was the only metastatic site in 28 (31%) cases and was associated with other sites in 63 (69%) cases. Median age was 62 yr in 61 male patients and 59 yr in 30 female patients. Thirty patients were submitted to an extensive investigation in search of the primary tumor, including systematic endoscopies: no primary cancer was found in these patients. In 61 other patients, only symptom-oriented investigations were performed and the primary cancer was found in 11 cases. The histologic type was adenocarcinoma in 71 (78%) cases, undifferentiated in 11 (12%) cases, epidermoid in 5 (6%) cases and determined by cytology alone in 4 cases. The median survival was 4 months in patients with metastases in the liver only, and 5 months in the other patients. This difference was not significant, so prognostic factors such as the Karnofsky index, weight loss, CEA and LDH levels were evaluated in the entire group; these factors do not have significant prognostic value. By contrast, when patients were able to receive chemotherapy, median survival was better (4 months) than without (median survival: 1 month; P = 0.005). In addition, in the case of objective response to chemotherapy, the median survival was 9 months versus 3.5 months for patients without objective response (P = 0.001). Seventy-three out of 91 patients (80%) were treated with chemotherapy regimen; 65 patients were evaluable: the objective response rate was 11 +/- 7% (7/65). Different regimens were used. With a non-toxic combination of fluorouracil, vinblastine and cyclophosphamide, 3 partial responses greater than or equal to 50% out of 43 patients (7 +/- 8%) were obtained. No significant advantage was observed when adriamycin was added to FU (4/13): 31 +/- 25%. Second- or third line chemotherapy regimen due to progression of the disease after the first-line combination provided only one objective response out of 36 patients. According to this retrospective study we recommend that overinvestigation be avoided in patients, with liver metastases of unknown primary site and that these patients be treated with non-toxic drug combinations.

Mitomycin C, a known inhibitor of DNA synthesis, was injected into white prepupae ofPhormia regina, Adults which developed from these prepupae showed alterations of the bristle pattern, loss of whole bristle organs, and the formation of bristles without sockets or sockets without bristle shafts. Dose-dependence was found for all modifications. For the abdominal microchaetae, the period of maximum sensitivity to the drug began at 16 h after puparium formation, that is well after all of the macrochaetae and most of the microchaetae of the thorax and the head had grown insensitive. Bristle forming trichogen and tormogen cells developed high degrees of polyteny with distinctly banded chromosomes. Photometric determination of the amount of Feulgen-DNA per nucleus led to estimations of DNA classes ranging from 256C to 2048 C. DNA contents of nuclei from Mitomycin C treated animals were significantly lower during the actual growth of the bristle apparatus, but reached approximately the same level as the controls prior to the time of emergence. Cytological investigations proved that doses of Mitomycin C which yielded bristle organs either without sockets or without shafts do not affect the differential division of the bristle mother cell. Polytene chromosomes damaged by Mitomycin C displayed a diffuse and irregular banding pattern. Possible modes of action of Mitomycin C on replicating polytene chromosomes are discussed.

Massive bilateral breast involvement in the course of a Burkitt's lymphoma is reported as an exceptional occurrence in a 13 year-old girl, in early puberty. It was an extensive form, stage IV, with massive organ involvement but without CNS involvement. Chemotherapy (LMB 84) induced total cure (18 months disease free survival).

The authors relate a case of gastric cancer on a 47 years woman, revealed by the presence of nerve roots metastasis whose evolution was fatal in 13 months. They are pointing out the singularity of this pathology as only 29 cases have been published to date. The clinical and radiological diagnosis must cancel the existence of paraneoplasic polyradiculoneuritis, only by histological examination of the roots. The primary cancer concerns often the breast, the lungs and the stomach. But 25% of cases remain unknown. Among the various terms proposed to define this neurological complication of visceral neoplasms, the authors are selecting the expression of "metastatic meningoradiculitis", as the best reflecting of the anatomical scheme.

Peripheral blood lymphocytes forming E rosettes in the presence of sheep red blood cells and those bearing surface immunoglobulins (SIg) have been studied quantitatively as an evaluation of T and B lymphocytes in Hodgkin's disease. 62 patients were investigated, 21 of whom before any treatment. It appears that the lymphocytes forming E rosettes are significantly lower in percentage in 86% of the patients and in absolute count in 65%. SIg bearing lymphocytes are elevated in percentile in 61% of the cases, but the absolute count is normal in 50% of the patients and elevated in 30% only. At diagnosis the T/B lymphocytes equilibrium is modified in 13 among 21 patients but, after the initial treatment of the disease, the ratio is modified in 90% of the patients in complete remission and remains unchanged for years even in the absence of relapse or immnunosuppressive treatment. It is suggested that SIg + lymphocytes from the peripheral blood are actually B lymphocytes and not anti-T-antibody coated T lymphocytes or antigen-antibody lacking of membrane markers, which are numerous in one third of the investigated patients, might be T lymphocytes with qualitative abnormality.

Histology and cytology show us the strong heterogeneity of non-Hodgkin’s malignant lymphomas (NHML). Numerous classifications have been proposed. They contain 6–12 classes [18, 25] which more or less match [5, 9, 10, 12, 17, 18, 20, 25]. If, with luck, a nonsophisticated and reproducible classification could predict the evolution, we would have to take it into account and suit the treatment to it. Nevertheless, none of the present classification systems are able to solve the problem for all the patients with NHML. The aim of a practical classification is to clearly distinguish the morphologic groups with the same predictable evolution possibly to cancel those in which the prognosis is still confused. Such well-defined groups have already been described, e.g., African Burkitt’s lymphoma [1], immunoblastic sarcoma [19], convoluted cell lymphosarcoma [18, 30], nodular well-differentiated lymphomas [4, 16], and histiocytosarcoma [22]. Nevertheless, it is still difficult to compare the potential evolution of the morphologic groups from one center to another. There are several causes: the reproducibility is not easy, the treatments are different, and even the frontiers of the disease are badly separated from the chronic lymphocytic leukemia or the acute leukemia.

The renal toxicity of antitumoral drugs is an increasingly disturbing problem. These drugs are now prescribed in an ever wider variety of cases, and delayed renal reactions, previously unknown, are revealed by the longer survivals obtained. For a number of years, patients whose cancer had been cured have been placed under haemodialysis on account of drug-induced renal failure. The renal toxicity of cisplatinum, nitrosoureas and methotrexate is well-known, but mitomycin C is also capable of inducing permanent renal failure; the delayed toxicity of this drug explains that it has long been underestimated. This example emphasizes the need for close co-operation between oncologists, nephrologists and pharmacologists in order to determine, for each patient, the most effective treatment with the minimum of side effects.

On the basis of cytologic studies of 144 patients with non-Hodgkin's malignant lymphomas (NHML), a cytologic classification was established that was composed of three groups (1, 2 and 3) containing nine classes (1A, 1B, 1C; 2A, 2B, 2C; 3A, 3B, 3C). Statistical analyses were carried out using 52 well-defined elementary cytologic characteristics. All the results given by the data-gathering procedures (hierarchical and dynamic clustering methods), by the descriptive analyses (multifactorial and canonical analysis) and by the stepwise discriminant analysis were in agreement with the proposed cytologic classification system. The most discriminating cytologic characteristics of the classes were the cell size, the nuclear-cytoplasmic ratio, the degree of cytoplasmic basophilia, the homogeneity of the cytoplasm and the number of mitoses. The use of these properties renders this classification system reproducible and applicable to clinical practice. A comparison was made between the cytologic classes and the NHML patients as grouped according to their clinical courses. Of the patients in classes 2A, 2B and and 2C, 94% showed acute leukemic characteristics. Of those contained in classes 3A, 3B and 3C, 78% showed poor prognosis or metastatic patterns. Of those contained in classes 1A, 1B and 1C, 76% showed a good prognosis pattern.

In untreated CML patients (at diagnosis or in relapse) we find about the same number of CFC per 1.10(6) nucleated cells in the blood and bone marrow (sometimes, slightly greater in the blood than in the marrow). Application of density-cut separation shows normal number of CFC in the low density fraction (Ldf-CFC) of bone marrow cells from patients in remission. In 7 untreated patients (at diagnosis or in relapse), we have always found a greater number of Ldf-CFC in the blood than in the marrow, when the study is performed on the same day and in the same technical conditions. This difference is observed even if the leukocytes count is elevated and thence, the contamination of bone marrow cells by blood cells is presumably important. The percentage of peripheral blood Ldf-CFC seems to be positively correlated with the number of peripheral blood leukocytes. The highest percentage of Ldf-CFC (greater than 60%) have been found in 5 patients in relapse. Two of these have entered into the blastic phase of CML and the three others relapse repeatedly in the chronic form of the disease.

Thirty-seven patients with primary unresectable bronchogenic carcinoma were treated by a combination, (“E.M.O.B.”), of cyclophosphamide (40 mg/k on day No. 1, or 13·3 mg/k × 3 consecutive days), methotrexate (7·5 mg/m2/d × 6 d, given orally for 6 consecutive days from day 21 to 26), Folinic Acid (15 mg/m2, IM, on day 27 at 8 p.m.). vincristin (0·7 mg/m2, IV at 8 a.m. on days 28 and 31) and bleomycin (10 mg/m2, IM at 2 p.m. on days 28 and 31, i.e. 6 hr after vincristin. The response was evaluated on day 48 and a new course started on day 49 if a regression or a stabilisation had been obtained. The 37 cases include 9 small anaplastic carcinomas, 24 squamous cell and large cell anaplastic carcinomas, and 4 cases of undetermined type. Thirty-one patients received almost 1 course of the schedule. Among them, 1 had a complete regression, 5 a regression of more than 50%, 6 a regression of less than 50%, 14 a stabilisation. There were 11 failures. Among 12 objective responders (39%) there were 4 squamous cell carcinomas (22%, median duration: 5 months), and 8 oat cell carcinomas (89%, median duration: 4 months). Four out of 37 patients (10%) were alive after 1 yr. The toxicity was evaluable in 32 cases representing 77 courses of the schedule: in 3 cases a severe toxicity led to an interruption of the treatment; strong (4 cases) or tolerable (15 cases) toxicity included nausea, vomiting and marrow depression. In 10 cases there were no toxic phenomena (31%). The over all results of this combination are not significantly better than those that may be obtained with cyclophosphamide or methotrexate as single agents or with vincristin and bleomycin in combination.

Addition of a daily dose of androgen in the form of 0.15 mg/kg of Stanzolol, given without interruption, gave an average survival of more than 4 years in patients suffering from granulocyte series acute leukaemias after complete remission was obtained. The simplicity of this treatment is apparent only from the appearance of marked manifestations of androgen impregnation in women from the 8th month of treatment onwards. These results, superior to those obtained up to the present time in the survival of myeloid leukaemias (non-lymphoblastic) were also better in terms of the stability and X "quality" of the remission in comparison to those obtained in acute lymphoblastic leukaemias. Confirmation of these results by controlled clinical trial will open up interesting perspectives, along side immunotherapy which remains of unproven effectiveness in myeloid leukaemias. The effectiveness of androgen stimulation of haematopoiesis as a stabilising factor of complete remissions in acute leukaemias has, in addition, interesting implications with regard to the theory of the leukaemic process.

An androgen (stanozolol: 0,15 mg/kg/d) was systematically associated to the treatment of acute non lymphoblastic leukemias, since the beginning of induction therapy (vincristin, daunorubicin, prednisone) and throughout the maintenance period (6-mercaptopurine and methotrexate). Thirty-six patients less than 60 years old (median age: 44 years) presenting with acute non-lymphoblastic leukemia were entered to the study. Sixteen achieved complete remission (C.R.), i.e. 44% of the whole and 53% of treated patients. Out of 16 patients with complete remission, 4 relapsed during the observation period which lasted 4-1/2 years. The stability of the hematologic equilibrium in patients in C.R. is the main finding of the present study. The actuarial curve of the duration of the first complete remission reaches a "plateau"; after the 8th month only one relapse was observed in 9 patients. The rate of C.R. at 2 years is 76 +/- 23%. As compared to the results from other schedules of treatment, this rate appears significantly better, specially in the case of immunotherapy (p less than 0,001). A prospective randomized study is now suggested as to confirm this result; its therapeutic and theoretical basis and perspectives are discussed.