Dual modulation of 5-fluorouracil with folinic acid and hydroxyurea in metastatic colorectal cancer.

Leucovorin and 5-fluorouracil (5-FU) can be further modulated with hydroxyurea. Sixty-eight patients with advanced colorectal cancer received every 2 weeks hydroxyurea per os 1.5 g to 2 g days -1, 1, and 2; leucovorin 200 mg/m2 iv over 2 hours started at least 1 hour after hydroxyurea and per os 100 mg/m2 12 hours later, on days 1 and 2; 5-FU, bolus 400 mg/m2 during leucovorin infusion and 24 hours continuous infusion 600 mg/m2, repeated on days 1 and 2. Two complete responses (7%), 8 partial responses (30%), 12 no change (44%), and 5 progressions (19%) were observed among 31 nonpreviously treated patients. Four partial response (11%), 15 no change (43%), and 16 progressions (46%) were observed among 37 pretreated patients. Nineteen were treated after progression on the same regimen without oral leucovorin and hydroxyurea, 1 achieved PR and 10 showed no change. Among them, 6 experienced response or stabilization of longer duration than with previous treatment. Twelve-month survival was 61% in non-pretreated and 43% in pretreated patients as of the start of chemotherapy. Toxicity was mild with nausea in 46%, diarrhea in 37%, and mucositis in 36%. The first-line response rate is in the range of leucovorin and 5-FU alone. Some pretreated patients benefited from this regimen.

[Chemotherapy and systemic treatments of cervical cancer]. / Chimiothérapie et traitements systémiques du cancer du col de l'utérus.

The prognosis of cervical cancer depends on nodal status and tumoral volume. Among patients with risk factors, chemotherapy seems promising, particularly with concomitant chemoradiation or neo adjuvant chemotherapy before surgery. The advent of treatments with combination of alpha interferon and 13 cis retinoid acid probably leads to a new therapeutic generation.

[Mixed endocrine tumor of the pancreas (vipoma, glucagonoma). Treatment by somatostatin followed by one of its long-acting analogs]. / Tumeur mixte du pancréas endocrine (vipome, glucagonome). Traitement par la somatostatine puis par un de ses analogues d'action prolongée.

We describe the 4-year follow-up of an endocrine tumour of the pancreas (vipoma-glucagonoma) treated with chemotherapy. To control the endocrine syndrome we used somatostatin 14 by continuous subcutaneous infusion for 1 year, followed by the somatostatin analogue SMS 201-995 administered alone without antitumoral chemotherapy. Under SMS 201-995 (100 micrograms 12-hourly) the endocrine syndrome dramatically improved. This effect persisted for 12 months after which a relative resistance to the drug developed. It was necessary to increase the dosage (300-400 micrograms/24 hours) and to alter the mode of administration (continuous subcutaneous infusion) to obtain a clinical benefit inferior to that obtained during the first year of treatment with SMS 201-995. At present this drug is given combined with recombinant interferon alpha 2A. In spite of computerized tomography, ultrasonography and monitoring of hormone levels we were unable to determine whether or not SMS 201-995 exerted a partial antitumoral effect.

[Transformation of malignant non-Hodgkin's lymphomas from low- to high-grade malignancy]. / Transformation des lymphomes malins non hodgkiniens de faible malignité en haute malignité.

Clinical and histological findings of six patients with low grade non-Hodgkin lymphoma (NHL) which transformed to high grade tumours are reported: 5 out of the 6 cases showed transformation from the centroblastic-centrocytic type to the centroblastic-polymorphic type (Kiel classification). Clinical aggressivity, large tumour mass, high frequency of extranodal sites of disease, systemic symptoms and resistance to treatment were observed. This type of transformation is not rare, estimated to be about 20 p. 100 of cases in the literature, and is more common than Richter's syndrome in chronic lymphocytic leukaemia.

[Treatment of advanced ovarian cancer]. / Traitement du cancer avancé de l'ovaire.

Forty patients with stage III or IV ovarian epithelial carcinoma, mean age 61 +/- 12 years, were treated either with cyclophosphamide-methotrexate-5-FU or with cisplatinum-adriamycin-5-FU-hexamethylmelamine. Median survival from initial surgery was 16 months, 18 months in stage III and 2 months in stage IV disease. 15 patients over 70 years had a median survival of 9 months. Median survival was higher with the regimen without cisplatinum (18 months against 13 months). Clinical response rate was 62.5%. Ten patients clinically free of disease underwent second look laparotomy which showed persistent disease in six. Based on these results and on a review of the literature, a new therapeutical approach is discussed.

[Cerebrospinal fluid in benign and malignant monoclonal dysglobulinemias]. / Etude des liquides céphalo-rachidiens dans les dysglobulinémies monoclonales bénignes et malignes.

The authors compared 9 cases of myeloma and 2 cases of Waldenström's disease with 10 cases of benign monoclonal gammapathies. None of the patients (except one) had neurological involvement; one patient hab diabetes. The study was focused on the immunoglobulins and proteins in the CSF. The following observations were made: - The CSF protein was raised in 8 out of the 11 malignant gammopathies and in 5 out of the 10 benign gammopathies; - An identical monoclonal protein was found in the CSF and serum in all the cases of malignant gammopathies. In the cases considered to be benign, the results were less concordant: one IgM lymphoma had normal CSF; three IgG dysglobulinemias had different immunoglobulins proteins in their CSF: - The mean CSF immunoglobulin level was much higher in the myeloma patients than in the benign gammopathies; - A number of findings suggest intrathecal secretion (at least in the malignant gammopathies). This is also true in a good number of the benign gammopathy cases. Direct tumoural invasion of the CSF may be more common than generally supposed. However, the study of CSF immunoglobulins alone does not establish the diagnosis of malignant dysglobulinemia. Nevertheless, the authors consider that the finding of intrathecal secretion of immunoglobulin, especially in patients with a discordance in FAB and FC fractions, should lead to a closer follow-up of these patients.

[Initial bone marrow involvement in Hodgkin's disease (author's transl)]. / L'atteinte médullaire initiale au cours de la maladie de Hodgkin. 25 observations.

Twenty-five patients with Hodgkin's disease and evidence of bone marrow involvement (BM +) were compared with 25 other Hodgkin patients, chosen at random, who had visceral lesions but free bone marrow (BM -). Both groups were observed throughout the same period. The first evaluation showed that bone marrow involvement was more frequent in male patients and that it produced medullary hypoplasia with WBC and platelet counts lower than in BM - patients. However, bone marrow involvement can only be ascertained by medullar biopsy. BM + patients were treated with multiple chemotherapy (mostly MOPP). Positive response was obtained in 64% and complete remission in 50%, as compared with 70% and 50% respectively in BM - patients. There was no significant difference in overall survival rate between the two groups. It remained in plateau at 50.5% after two years in BM + patients and at 63% after 27 months in BM - patients. When complete remission was obtained the survival rate after one year was 90% for BM + patients and 100% for BM - patients. In the absence of complete remission, however, the median survival time was inferior to one year in both groups. The dosage levels and side-effects of chemotherapeutic agents were similar in both groups, but cytopenia was more pronounced in BM + patients.

[Two cases of agnogenic myeloid metaplasia associated with chronic lymphocytic leukemia (author's transl)]. / Association de leucémie lymphoïde chronique et de splénomégalie myéloïde. A propos de deux observations.

Two cases of agnogenic myeloid metaplasia associated with chronic lymphocytic leukemia are reported. Both cases are documented by clinic, bone marrow biopsy, immunologic and isotopic studies. Such observations allow to point out the lymphoproliferative pattern that can be found among any agnogenic myeloid metaplasia. It is suggested that this disease includes a monoclonal lymphoid proliferation which may become the prevailing symptom.

[Comparative trial between two drugs in the treatment of vomiting induced by anti-cancer chemotherapy (author's transl)]. / Essai comparatif de deux médicaments dans le traitement des vomissements induits par la chimiothérapie anti-cancéreuse.

In order to prevent vomiting induced by anti-cancer chemotherapy, the efficiency of domperidone has been compared to metoclopramide in a randomised trial. No difference has been observed between both emetic treatments.

[Extra skeletal Ewing's sarcoma. Report of two cases. Ultrastructural study of one case (author's transl)]. / Les sarcomes d'Ewing extra-osseux. A propos de deux observations dont l'une avec étude ultrastructurale.

The authors report two cases of extra skeletal Ewing's sarcoma. The first case concerns a 26 years old woman presenting a tumor at the level of the sacrum area, locally recurrent, metastazing to the lungs and the lumbar column, despite of radiotherapy and chemotherapy and leading to death after a course of 18 months. The second one is that of a 30 years old man bearing a tumor of the shoulder area probably already metastazed to bones, rapidly recurrent and metastazing to the lungs and cause of death after 9 months in spite of intensive therapy. About these 2 observations a review of the literature of the cases of extra skeletal Ewing's sarcoma is done. Whatever nosologic discussion it seems that Ewing's sarcoma may present essentially as a tumor of soft tissues. An ultrastructural study has been performed in the second case. The findings are similar to those reported in Ewing's sarcoma.

[Very long survivals of chronic granulocytic leukemia (author's transl)]. / Les survies très prolongées de leucémie myéloïde chronique. Revue de la littérature avec étude des facteurs pronostiques, a propos d'une observation d'une durée de 18 mois et demi.

Following busulfan induced bone marrow insufficiency, a patient witha chronic granulocytic leukemia (CGL) has had a survival lasting 18.5 years. During remission, chromosome studies on bone marrow have not shown Philadelphia chromosome (Ph 1). There was no correlation between this observation and initial pronostic factors from literature. Analysis of 14 cases (13 from literature) of prolonged survival showed that Ph 1 was absent in 4 cases when only 15% of CGL are initially Ph 1 negative. Therapeuticcaryoconversions were probable. Recently attempts have been made to eradicate the abnormal Ph 1 positive clone. Some hopeful results are reported.

[Meningeal leukemia during acute promyelocytic leukemia (author's transl)]. / Méningite leucémique au cours d'une leucémie aiguë promyélocytaire.

The authors report the case of a meningeal leukemia occuring during the remission stage of an acute promyelocytic leukemia. The data from literature about the meningeal leukemia of acute granulocytic leukemias, the expected long survival of acute promyelocytic leukemias lead to think that this meningeal complication must be systematically prevented.

[Primary biliary cirrhosis associated with acute disseminated lupus erythematosus (author's transl)]. / Cirrhose biliaire primitive associée à un lupus érythémateux aigu disséminé. 1 observation.

A 39 years old man experienced typical primary biliary (P.B.C.). Additional symptoms occured during the next four years including constitutional symptoms, polyarthralgias, nephrotic syndrom and chronic polyarthritis. Biologically, at the beginning of the disease, antimitochondrial antibodies were at the titer of 1/50,000, and the antinuclear antibodies at the titer of 1/10,000 (speckled pattern). During the course of the disease antimitochondrial antibodies decreased progressively and disappeared at the last control. The antinuclear antibodies progressed until 1/500,000 with anti Sm specificity. The association of P.B.C. and S.L.E., very seldom mentioned in the literature, is discussed among the auto-immune diseases.