Biomedical subjects
Publications and source records attributed to L Meeus.
We used the test-dose method to calculate the dose of methotrexate to administer to the patients to reach the therapeutic but non-toxic blood concentration of 10(-5) mol/L. Methotrexate was tested with a radioimmunoassay technique and in 19 out of 20 patients we obtained the desired plateau during 24-h infusion.
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Adriamycin is known to be effective in the treatment of breast cancer. Serial radionuclide determinations of the left ejection fraction can provide advanced warning of adriamycin cardiotoxicity, prior to clinical signs of the left ventricular dysfunction. Patients at high risk of congestive heart failure can be detected. Depending on the results of the second course of chemotherapy, guidelines and criteria can be laid down to predict the appropriate time for drug discontinuation.
Among the neurological side-effects, peripheral neuropathy is a result of therapy with vindesine and above all vincristine. Although in most cases it is responsible only for paresthesias, it may cause extensive paralysis and requires that the drug be discontinued. These drugs may also affect the neurovegetative system. Ototoxicity may be seen with cis-platinum and vigilance disturbances with L-asparaginase. Genetic consequences are mainly due to alkylating agents. These agents almost constantly impair male and female fertility but recovery is possible. Libido is also affected with the attendant psychological consequences. The offspring of patients previously treated by chemotherapeutic agents are normal. Development of secondary carcinoma or leukemia is currently a major concern. Secondary malignant disease may develop after the treatment of any cancer, especially if radiotherapy was associated with alkylating agents. Leukemias are of the acute myeloid type and usually follow a preleukemic phase. A table summarizes the main toxicities of the most usual drugs.
Aplastic anemia is the most severe hematologic side-effect. All chemotherapeutic agents, with the exception of bleomycin and L-asparaginase, may induce aplasia, but the degree of hematotoxicity varies according to the drug. With the exception of acute leukemia in which drug-induced aplasia is part of the treatment, aplasia must be prevented through perfect knowledge of the posology and injection schedules for each drug, as well as by adjusting doses to the patient's hematological status. If aplasia develops, intensive hematological care is requisite. The most common cardiac side-effect is toxic cardiomyopathy caused by anthracyclines, which must be diagnosed early by EKG recordings before each injection and repeated ultrasonography or dynamic cardiac scintigraphy. The risk of toxic cardiomyopathy makes it requisite not to exceed the maximal doses set for each drug. Pulmonary side-effects include acute hypersensitivity pneumopathy and chronic diffuse interstitial fibrosis, the latter being more common and mainly caused by bleomycin. The risk of chronic fibrosis demands that patients be closely monitored and that the total dose be kept under 300 mg. Renal toxicity usually results in acute transient renal failure, as with cisplatinum, and requires a thorough biological study before each injection. Vesical hemorrhage, which is threatening in some instances, may occur with cyclophosphamide. VM26 and VP16 may induce anaphylactic shock. Allergic symptoms are possible with L-asparaginase and bleomycin.
The recent development of chemotherapy in the treatment of cancer and leukemia requires that all practitioners involved have a thorough knowledge of the sometimes life-threatening side-effects of chemotherapeutic agents. All these agents, whether used alone or in a combination, carry a risk because of their lack of specificity which make active on normal cells, especially those with a rapid turn-over such as the hematopoietic cells or the cells of the digestive tract. Prior to the prescription of a chemotherapeutic regimen, the acceptable risk must always be clearly defined, according to the seriousness of the disease and to the patient's age, physical condition and psychological status. During the course continuous monitoring adjusted to the specific toxicity of the agents used is requisite. More or less prominent asthenia and weight loss are common, as the result of various physiopathological mechanisms. Digestive disorders may consist only of nausea and emesis or include mucosal lesions with diarrhea as the main feature. Vincristine and vindesine are responsible for constipation. Hepatic toxicity, which is less common, is usually due to L-asparaginase. Transient hair loss is the most frequent cutaneous side-effect. Hyperpigmentation, photosensitivity, nail lesions, cellulitis and ulcerations may occur, as well as specific lesions with bleomycin. High fever during injection often occurs with this last agent.
In a randomized multicenter trial, 151 patients, with advanced epidermoid carcinoma of the head, neck and oesophagus, were treated with an association of vincristin, methotrexate, bleomycin and cis-platin (group I) or detorubicin (group II). Prognostic factors were equally distributed for the both groups. Partial or complete responses were obtained in 22 patients of group I (29 p. cent) and 9 in group II (12 p. cent, p less than 0.05). Objective response rates were higher in untreated patients or those in good condition but the difference was not statistically significant. Five probably treatment induced deaths (3 p. cent) were observed. Treatment was stopped in 2 patients (15 p. cent) for haematological, general or digestive toxicity. This trial confirms the efficacy of vincristin, methotrexate, bleomycin and cis-platin for advanced head and neck carcinomas.
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The cardiac complications of radiotherapy have been reviewed in the light of 46 case histories collected from 16 treatment centres in France. They are usually found after radiotherapy for Hodgkin's disease and carcinoma of the breast. Although histologically there may be diffuse fibrosis involving the endocardium, myocardium and pericardium, it is pericarditis which is the usual clinical feature. It often occurs late, and takes many forms. The dry constrictive fibrous type of pericarditis is the most severe because of the amount of myocardial fibrosis usually associated with it. It is rare for there to be clinical features of myocardial fibrosis, and if present they are variable: isolated disorders of repolarisation or of conduction, or true cardiomyopathies. Lesions of the coronary arteries are exceptionally rare after radiotherapy, and involve fibrosis of the intima or atherosclerosis.
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A case of extracranial vertebral artery dissection is reported, presenting with headache and pulsatile tinnitus, without ischemic events in the vertebrobasilar system.
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