Second malignancy after cisplatin, vinblastine, and bleomycin (PVB) chemotherapy: a case report.
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Biomedical subjects
Publications and source records attributed to G M Mead.
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The role of chemotherapy in the management of head and neck cancer includes treatment for recurrent disease and as an adjunct to conventional therapy with radiation and/or surgery in the primary treatment program. The best single agents, methotrexate and cisplatin, used for recurrent disease give response rates of 20 to 50 percent but of short duration. Results may be improved with combination chemotherapy, but often with increased toxicity. Prognostic factors that influence response are discussed. A newer role of chemotherapy in this disease is in the initial treatment program. Pretreatment chemotherapy can debulk these lesions prior to surgery and/or irradiation in up to 80 percent of patients. Controlled trials are in progress to determine the effect on cure rates. Chemotherapy utilized during radiotherapy has resulted in survival benefit in several studies. Post-treatment adjuvant chemotherapy still needs to be evaluated. The potential advantages and disadvantages of chemotherapy used in the initial treatment are discussed. Major strides have been made in the last decade in the treatment of head and neck cancer, and chemotherapy is assuming an increasingly important role.
Eighty-one patients with germ cell tumors or ovarian carcinoma were treated over a 4-year period with cisplatin-containing combination chemotherapy. Eight patients (9.8%) experienced epileptic seizures during or within 3 months of this chemotherapy. While a definite causal relationship between the seizures and cisplatin could not be established, we have rarely seen such episodes in relationship to other cytotoxic drugs. A number of possible contributing factors were apparent, including hyponatremia and pretreatment impairment of renal function.
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Antibody to tubulin in man has been studied using a specific radioimmunoassay, affinity chromatography radioimmunoassay but markedly increased levels were noted in patients with infectious mononucleosis where the antibody was predominantly IgM in type. This finding was confirmed on fluorescence microscopy. Affinity chromatography purified antibody produced characteristic microtubular staining of fixed 3T3 cells, but in addition, produced weak staining of cryostat sections of rat tissue, similar in distribution to that of smooth muscle antibody. Our studies indicate that the IgM smooth muscle antibody found in infectious mononucleosis by IF techniques is at least in part due to an antitubulin antibody.
A solid-phase double antibody radioimmunoassay capable of measuring antibody to tubulin, the principal component of microtubules, is described. This assay is simple, combining sensitivity with specificity and also allowing determination of antibody subclasses.
Drug histories were taken from 100 patients in their first attack of acute pancreatitis, and each was matched with a control subject of the same sex who was admitted to hospital as an emergency with acute abdominal pain, whose serum-amylase was within the normal range, and whose age was within three years of the pancreatitis patient's. The major differences between the patient groups was in the use of cardiovascular agents, and this was primarily due to a statistically significant excess of diuretic takers among the pancreatitis patients. There was an associated excess of intake of digoxin and antihypertensive and anti-anginal agents, but neither difference was statistically significant. Other categories of drugs showed no substantial differences. The difference between the pancreatitic patients and controls is almost entirely accounted for by takers of cyclopenthiazide with potassium chloride and of frusemide, especially the former. Further clinical and experimental evidence is required before the role of diuretics and/or potassium chloride in causing acute pancreatitis can be determined.
No abnormality was found in 76 of 100 dyspeptic out-patients under the age of 50 who underwent barium meal examination, while various non-malignant lesions were found in the remaining 24. Only 10% of those under 30, and 10% of those with symptoms for less than a year proved to have any abnormality. Because of the radiographic results treatment was altered in only 11 patients, and most of these changes were small.
All patients with subdural haematoma presenting to medical wards in Nottingham over a 5-year period have been reviewed. Of twenty-one such patients eight were first diagnosed at post-mortem, whilst all of the remaining thirteen patients in whom the diagnosis was made in life survived following neurosurgical evacuation of the haematoma. Diagnostic failure was caused mainly by failure to consider the possibility of subdural haematoma or misinterpretation of negative investigations. An attempt has been made to characterize the clinical patterns that may suggest the presence of a subdural haematoma, and recommendations are made on the investigation of such patients.
Thirty-one (58 per cent) of a group of fifty-three unselected patients with stage II-IV favourable prognosis non-Hodgkin's lymphoma were regarded as being eligible for a prospective study of no initial therapy. Seventeen of these patients (55 per cent) have required no treatment for periods from 6 + -47 + months, (median 18 months) and fourteen patients have been treated with chemotherapy for progressive disease after a period varying from 3-40 months (median 9.5 months). Selected asymptomatic patients with non-bulky disease may be suitable for no initial therapy. Randomized prospective trials will be needed to test whether survival is affected by delaying therapy.
One hundred and thirty-seven patients with small cell carcinoma of the bronchus underwent bone marrow trephine and/or aspirate examination as part of their clinical staging. Twenty-four patients (17.5 per cent) were found to have malignant marrow infiltration. In no case was this an isolated finding of metastatic disease, indeed most patients had gross metastatic spread to liver and/or bone. Marrow infiltration has not been shown to be a major prognostic factor in response to chemotherapy or survival in previous studies. We recommend that this staging procedure be discontinued in routine clinical practice, and instead be confined to specific indications in clinical trials.
BACKGROUND: Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment. METHODS: Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n=904) or one injection of carboplatin (n=573; dose based on the formula 7x[glomerular filtration rate+25] mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214. FINDINGS: 885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3.0-4.9), relapse-free survival rates for radiotherapy and carboplatin were similar (96.7% [95% CI 95.3-97.7] vs 97.7% [96.0-98.6] at 2 years; 95.9% [94.4-97.1] vs 94.8% [92.5-96.4] at 3 years, respectively; hazard ratio 1.28 [90% CI 0.85-1.93], p=0.32). At 2 years' follow-up, the absolute differences in relapse-free rates (radiotherapy-chemotherapy) were -1.0% (90% CI -2.5 to 0.5) by direct comparison of proportions, and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1.96% [95% CI 1.0-3.8] vs 0.54% [0.1-2.1], p=0.04). One seminoma-related death occurred after radiotherapy and none after carboplatin. INTERPRETATION: This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years' follow-up.