Biomedical subjects
Publications and source records attributed to T Pignon.
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Colorectal adenocarcinoma are rare in Madagascar. Over a period of 8 years, such tumors were treated in the cancerology and surgery departments of Antananarivo. The low incidence and the relative young age at the time of diagnosis are comparable to observations made in other developing countries. Men represent 47 of the cases and women 34. On the average, patients were 52.3 years old (range: 23-78 years). The most frequent early symptoms are rectorrhagia (26 cases) for rectal cancer, abdominal pain (9 cases) and transit bowel disorders (9 cases) for colon cancer. Between the first symptom and diagnosis, the average delay is 8.5 months (range: 2 days-37 months). No risk factor was found. Thirteen patients did not receive any treatment, 8 were only submitted to radiotherapy and 60 were surgically treated with a curative intent in 26 cases, a palliative one in 32 cases and for diagnosis in 2 cases. Among the 63 tumors available for modified Dukes' classification of Astler-Coller, 9.5% are stage B1, 23.8% are stage B2, 11% are stage C1, 15.9% are stage C2 and 39.7% are stage D; there are no stage A. There is no epidemiological particularity for these cancers in Madagascar. The poor prognosis is probably mainly related to a lack of appropriate medical and surgical facilities.
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Determination of methotrexate (MTX) kinetics after an IV bolus (50 mg/m2) allows prediction of the steady-state plasma level of this drug during a constant infusion. This prediction allows high-dose MTX (HD-MTX) therapy without major toxicity. Patients with head and neck carcinoma received HD-MTX and vindesine (VDS) infusions concomitantly. The therapeutic survey of these patients showed that the predicted plasma level of MTX was not achieved in the presence of VDS. Moreover, the computed dose of MTX had to be increased by a larger amount if the MTX plasma clearance after the identification IV push was low (less than 9 l/h). In the presence of VDS, the creatinine clearance is lower than when MTX is infused alone, and MTX renal elimination is identical (MTX or MTX + VDS infusions). Thus it seems that the decrease of the MTX plasma level during MTX-VDS infusion could be due to an increase of cellular incorporation.
The immunocompetent subrenal capsule assay tumour graft is a good chemosensitivity test. We have compared it to immunocompetent white hamster cheek pouch tumour graft. These two assays are both easy to perform. Each has specific advantages and disadvantages. However the six days immunocompetent mouse subrenal capsule assay tumour graft is the most practicable and reproducible. The hamster cheek pouch assay would be used when mouse subrenal capsule assay would not be efficient for the molecules under study.
It now seems possible to predict response to anti-cancer drugs by means of several methods classified into three groups. Methods in the first group are aimed at determining the intracellular mechanisms required for the drugs to act on the tumoral cells; apart from hormone receptor assays, few of these have practical applications. Methods in the second group are concerned with the action of cytostatic drugs on malignant cells; clonogenic cultures and human tumour xenografts in mice are already routinely used. Finally, methods to evaluate the pharmacokinetics of anticancer drugs are being developed. These three groups of methods can be used in the pre-clinical screening of these drugs or at the clinical trial phase to predict individual responses to chemotherapy.
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A clinical trial of NPT 15392, a purine derivative, was run in ten head and neck cancer patients presenting signs of immunosuppression and undergoing repeated chemotherapy. A battery of ten tests was used to assess the immune status of the subjects. Those tests included skin tests, lymphocyte investigations (count, E-rosetting, membrane fluorescence and lymphoblastic transformation) and determination of serum levels of C'3 fraction of complement and IgA. The drug induced transitory, immune stimulation during or after treatment without any side effects. NPT 15392 seemed to selectively exert an action on T lymphocytes. Inasmuch as transitory, immune stimulation and secondary immune depression were noted after treatment, the therapeutic protocol for use of this drug should be reexamined.
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