Tactics in cancer treatment: Introduction.
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Biomedical subjects
Publications and source records attributed to G Mathé.
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A combined treatment modality incorporating surgery plus BCG immunotherapy was administered to (DBA/2 X C57B/6) F1 mice grafted with EAkR lymphosarcoma. 30% of mice survived free of disease when BCG was injected intravenously two days after operation consisting of tumorectomy plus excision of the regional lymph node performed on the 8th day after tumor inoculation. Similar results were obtained when BCG was injected subcutaneously 6 days before surgery. Pre-operative intravenous and post-operative subcutanous BCG administration failed to cure the animals just as BCG or surgery alone.
One thousand and twenty four patients with disseminated breast cancer were submitted to combination chemotherapy. Fifty one patients (group I) were sequentially given VCR, CPM and 5 FU, and seventy three patients (group II) were given ADM, VCR, CPM and 5 FU. The general and haematological tolerance was good and comparable in the both groups of patients: we observed only two severe infectious complications. Bonemarrow hypoplasia, six myocardial ischemia (two of them were lethal) in each group of patients, without any predominance in the group of patients treated with adriamycin. The percentage of objective regression in both groups was respectively: 72% and 71%. The mean duration of response was eight months. The median survival time was 420 days for patients of group I; for patients of group II the median is not obtained at 480 days. This study confirms that responders to chemotherapy significantly increase the mean duration of survival time. However, in this group of responders the presence of the liver metastases is worse prognosis than all other visceral metastases.
Forty-three patients with inoperable and/or recurring malignant gliomas, and 30 patients with multiple recurring brain metastases were treated with a combination of adriamycine (45 mg/m2) and 4-dimethyl-epipodophyllotoxin D-thenylidene (VM 26) (60 mg/m2 for 2 days) with 1-(2-chloroethyl) -3-cyclohexyl-1-nitroso-urea (CCNU) (60 mg/m2 for two days). These cycles of treatment were repeated as soon as the hematological restoration was complete. The treatment was well tolerated and the clinical condition of 31 out of 43 glioblastoma patients improved during the two months after the beginning of the treatment. Six out of eight patients with breast cancer metastases, one out of 13 with bronchial cancer metastases and three out of nine with other types of cancer metastases also benefitted from the treatment. Examination of the results obtained reveals the following characteristics: -A low degree of efficiency of the combination in the treatment of brain metastases, except for breast cancer metastases. -Absence of complete correlation between the clinical results observed and the cinegammagraphic developments. -Similarity of the results independent of the initial localization. -Establishment of a six-months median survival period, with ten patients at present in a state of apparently complete remission, 180 to 506 days after beginning of the treatment.
Angio-lymphoblastic lymphadenopathies are a newly described haematological entity, though not rare, characterised by a histological triad (vascular neogenesis, highly polymorphic or predominantly immunoblastic cellular proliferation and the presence of acidophilic protein deposits), a clinical syndrome consisting essentially of voluminous disseminated lymphadenopathy and hepatosplenomegaly and abnormal laboratory findings dominated by a polyclonal dysproteinaemia. This disorder, the first four French cases of which are described here, does not appear to be malignant in its early stages and is sensitive to corticosteroid therapy at that time. Secondary sarcomatous transformation is possible.
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Out of 64 patients with non resectable epidermal bronchus carcinoma, 26 patients had before any treatment positive responses of skin tests to recall antigens. In these patients we found a correlation between the reactivity of the skin tests, the presence of seric factor inhibiting the leucocyte migration, the mean count of peripheral lymphocytes and the response to combination chemotherapy protocol. The patients who respond to treatment have a significantly better prognosis than the patients who do not respond. With this correlation it seems to be possible to distinguish between two populations of patients with non resectable bronchus carcinoma : one population with a good risk who can be significantly improved by the treatment : the other population with a very severe prognosis.
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Children with acute lymphocytic leukemia (ALL) in remission and undergoing either chemotherapy or immunotherapy were tested for general cell-mediated immunocompetence and cell-mediated reactivity to tumor-associated antigens (TAA) using the following parameters: skin tests with recall antigens and extracts of lymphoblastoid cell lines; primary sensitization to dinitrofluorobenzene and picryl chloride; in vitro tranformation by mitogens and PPD; and lymphocyte-mediated cytotoxicity against a lymphoblastoid cell line and a panel of cryopreserved leukemic blasts. Reactivity in all assays of children on continuous chemotherapy was significantly depressed compared to similar patients later in the study. Patients on intermittent chemotherapy demonstrated much less immunodepression. The groups tested early during immunotherapy with BCG and allogeneic leukemic blasts were hyper-responsive (compared to published data) to primary sensitization with picryl chloride. Skin test reactivity to recall antigens and to tumor-derived lymphoblastoid cell lines was suppressed (as analyzed serial comparison) in this hyperimmunized group, possibly due to antigenic competition, and reactivity in all other assays was normal. The patients tested after 2-8 years of immunotherapy showed significantly higher positive skin-test responses to extracts of tumor-derived lymphoblastoid cell lines as compared to the other groups. The results of this multiphasic screen support the known effects of chemotherapy on immunocompetence. Moreover, they document the prompt return of immunocompetence with intermittent chemotherapy and during immuno-therapy. These results do not, however, indicate a striking augmentation of the immune response during immunotherapy as measured by these parameters.
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Six systemic adjuvants of immunity were tested for their ability to induce macrophage activation. Four of them: living BCG, hydrosoluble extracts from BCG (HIU II) and from M.smegmatis (IPM), and lipopolysaccharide from E.coli (LPS), when administered to normal mice render macrophages non-specifically cytotoxic for tumor cells in vitro. The intensity of this phenomenon varied according to the route and time of adjuvant administration. In contrast, lentinan extracted from Lentinus edodes, and levamisole which is a synthetic chemical compound, depressed macrophage cytotoxic potential. BCG, IPM and LPS were shown to have a direct action on macrophages. After in vitro exposure to these agents, the cytotoxic potential of normal macrophages was greatly increased. Levamisole was unable to stimulate this macrophage function directly in vitro. On the other hand, such a macrophage activation has been induced in vitro when normal macrophages were cultivated in the presence of MIF coming from the supernatant of human lymphoblastoid cell lines.
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