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Biomedical subjects

M Hayat

Publications and source records attributed to M Hayat.

At least 145 records · Page 8Linked to original sources

[Treatment of rectocolic and gastric adenocarcinomas with 5-fluorouracil associated with high doses of folinic acid. Results of an experimental study].

We report the results of a therapeutic trial in patients with rectocolic and gastric metastatic adenocarcinomas. This trial is based on experimental evidence that an excess of reduced intracellular folic acid increases the cytotoxicity of fluoropyrimidines. The treatment consists of 5-fluorouracile (5-FU) (370 to 400 mg/m2/24 h) and folinic acid in high doses (200 mg/m2: 24 h) given simultaneously for 5 consecutive days; the interval between courses is 21 days. Thirty patients with measurable rectocolic adenocarcinomas were evaluated. They were divided into two groups: 16 patients had had no previous chemotherapy and 14 had not responded to chemotherapy with 5-FU alone or associated with other cytostatic drugs. Response rates were 56% in the first group and 21% in the second. Five patients with measurable gastric adenocarcinomas were also evaluated; none had received previous chemotherapy. A partial response was recorded in three of these patients. Toxicity of the therapeutic regimen was acceptable. Stomatitis was the most common toxic side-effect. In patients with severe adverse side-effects recurrence was efficiently prevented by decreasing the daily dose of 5-FU to 30 mg/m2 during subsequent courses. We conclude that in the tumors studied folinic acid in high doses can improve the antitumoral effect of 5-FU and induce a response to this agent in some rectocolic tumors which were previously resistant.

Adenocarcinoma↗

[Aclacinomycin-A in acute leukaemias and leukaemic non-Hodgkin lymphomas (author's transl)].

Aclacinomycine-A (ACM), a new anthracycline derivative, was administered intravenously to 50 patients in doses of 10-30 mg/m2/day for periods of 6 to 30 days. Among the 45 patients who could be assessed, 17 were suffering from acute myeloid leukaemia, 19 from acute lymphoid leukaemia and 9 from non-hodgkin lymphoma. The results confirmed those first published by the authors in 1978 and led them to propose new measures aimed at reducing the toxicity of ACM. Depending on the dosage, complete or partial (more than 50%) remissions were obtained in patients with acute myeloid leukaemia. In the 19 patients with acute lymphoid leukaemia, complete remission was observed in 2 and partial remission in 2. Among the 9 patients with non-hodgkin lymphoma, there was 3 complete and 1 partial remissions. ACM did not produce alopecia and, as predicted by the authors' experimental study on hamsters, did not have major cardiac toxicity. The gastrointestinal toxicity, which had forced a reduction of the total dose in the first trial, proved moderate, even with normal dosage.

Aclarubicin↗

[Treatment of leukemias and lymphomas with interferons: I. Trial of myeloma therapy with human beta-interferon].

Eighteen patients with malignant gammapathies (16 with myeloma and 2 with Waldenström's disease) for a short time because in a phase II-I trial were treated with human (IF beta) given i. v. 6 X 10(6) units weekly (7 patients) or 3 X 10(6) units twice weekly (11 patients) during at least 3 months if tolerated. Treatment was discontinued because of side-effects in three patients. Reduction of the M component of at least 25% from the initial value was obtained in 3 patients. In one case, was also observed in disappearance of the urinary Bence-Jones protein, in 4 cases a significant reduction of bone marrow infiltration by plasma cells and, in 5 cases, major alleviation or disappearance of bone pain. Length of treatment seems an important factor for activity. Immune monitoring with currently available tests, mainly NK cell activity, yielded no correlation with therapeutic effect in these patients. This very preliminary study demonstrates the effect of fibroblastic interferon in myeloma, but further studies are mandatory to determine the population of patients likely to benefit from treatment, the best modalities, possible special indication, dose schedule and duration of treatment. Interferon, however, already appears in this population of patients as giving results similar to those of single agent chemotherapy. As it is not myelosuppressive, it could be indicated in that frequent situation of advanced myeloma with bone marrow failure contra-indicating combination chemotherapy.

Clinical Trials as Topic↗

[Sequential chemotherapy and radiotherapy modalities in small cell lung carcinoma. Preliminary results].

Two non randomized therapeutic trials have been conducted in oat cell carcinoma of the lung with limited disease. The first protocol combined chemotherapy (adriamycin, cyclophosphamide, VM 26, procarbazine) with mediastinal and supra-clavicular radiotherapy in classical fractionation (40 grays in 4 weeks). The second combined a more intensive chemotherapy (adriamycin, VP 16, methotrexate, cyclophosphamide) with an alternating radiotherapy (3 series of 15 grays). All patients received prophylactic brain irradiation. Preliminary results show a 9 month survival rate of 34 per cent and 62.5 per cent respectively. In addition, all patients in the second protocol presented a complete response at the end of the induction treatment. These preliminary data encourage proceeding with this kind of combined treatment.

Antineoplastic Agents↗

[Treatment of leukemias and lymphomas with interferons: III. Trial treatment of meningeal localizations of acute leukemia and non-Hodgkin's lymphomas with beta interferon administered by the intrathecal route].

Six patients with pure meningeal relapse of acute lymphoblastic leukemia (ALL) (5 patients) or leukemic lymphosarcoma (LS) (non Hodgkin's lymphoma) (NHL) (1 patient) were treated with intrathecal (I.T.) human fibroblastic interferon (IF beta), one vial (1.3 million units) every other day or every day up to remission or failure. Tolerance was excellent in all six patients with no local or general side effects. 5 patients had no improvement of their meningeal blast infiltrations after 5 to 8 injections and were given IT chemotherapy. The sixth patient achieved a complete remission (CR) after 11 injections, and was maintained in CR for eleven months under systemic and IT chemotherapy. IF cannot be proposed as standard treatment for meningeal leukemia, but we may be able to select a population of patients in which it could be indicated. Its combination with methotrexate and arabinoside cytosine, the two agents used IT which are S-dependent, has to be studied for a possible potentiation. Moreover, its good tolerance would permit its use in severe meningeal viral diseases.

Acute Disease↗

Vindesine: a new vinca alkaloid.

Vindesine (VDS) is an analogue of the vinca alkaloids. Its spectrum of antitumoral activity is similar to that of vincristine (VCR), but with milder experimental neurotoxicity, and it inhibits the polymerization of tubulin. Its terminal half-life is 24 h and its plasma clearance is intermediate between those of vinblastine (VLB) and VCR. The maximal tolerated dose is 4-5 mg/m2/week, the dose-limiting toxicity being myelosuppression (nadir by days 7-8 and recovery by days 11-13). It has already been demonstrated as efficient in childhood acute lymphoid leukemia (ALL), non-Hodgkin's lymphoma, blastic crisis of chronic myeloid leukemia, and esophageal carcinoma. It has also shown activity in Hodgkin's disease, breast and germ cell carcinomas, and melanoma. Intolerance is mainly neurologic, with paresthesias, without motor impairment, or hematologic, with leukopenia, and sometimes alopecia, asthenia, and muscle pains. The results are better if the patients have not been treated previously; continuous infusion could be of interest and there appears to be no cross-resistance with its parent VCR, as documented in ALL.

Animals↗

Cisplatinumdiamminodichloride (CPDD) in chemotherapy of cancers: a phase II therapeutic trial.

We have conducted a phase II trial of cisplatinumdiamminodichloride (CPDD) which not only demonstrated its remarkable activity in embryonic carcinoma of the testes, but also in ovarian carcinoma, in melanoma, and in epidermoid carcinoma, especially of the head and of the uterus cervix. Its toxicity, manifested mainly in the digestive and renal tracts, confines its administration to hospitalized patients only. This compound is now indicated in combination therapy for the above-mentioned tumors.

Adolescent↗

Ultrastructural study of the cardiotoxicity and light-microscopic findings of the skin after treatment of golden hamsters with seven different anthracyclines.

Golden hamsters were administered seven anthracyclines: adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), rubidazone (RBZ), aclacinomycin (ACM), and N-trifluoroacetyladriamycin-14-valerate (AD-32), three times a week during 4 weeks, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. We examined their myocardia by electron microscopy (EM) and their skin by light microscopy (LM), and report here the findings of these two examinations. The mortality was very high for the groups of hamsters treated with ADM, DTR, DRB, eADM, and RBZ (all treated hamsters died before the end of the fourth week) and very low for those treated with ACM and AD-32 (for each drug, only one of the 21 treated animals died after 4 weeks of treatment). After the first week of treatment and chiefly after the second week, all treated hamsters, except those treated with ACM, showed very severe EM alterations of their myocardia. EM detected almost no early myocardial lesions in ACM-treated hamsters but, after 4 weeks of treatment, severe cardiac lesions also appeared which, like those after AD-32, were nonlethal and reversible. LM of the skin detected degenerative lesions with atrophy of all epidermic layers and a loss of the hair (alopecia) in all treated hamsters except those treated with ACM and AD-32; the skin in these two groups preserved its normal histologic structure. These observations agree with phase I-II clinical ACM studies in which the rate of ECG abnormalities was 4.5% and the rate of alopecia 0%, and with an early AD-32 clinical study conducted by Blum [3].

Animals↗

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial].

We have conducted a phase II trial of cisdiammino-dichloro platinum (CDDP) which demonstrates its remarkable activity in testis embryonic carcinoma, in ovary carcinoma and in epidermoid cancers, especially head and neck and uterus cervix carcinoma. Its toxicity in mainly digestive and renal. This compound is now indicated in combinations in the case of the above mentioned tumors.

Adolescent↗