[Back pain and medullary compression in patients with cancer].
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Back Pain↗
Biomedical subjects
H H Hansen
Publications and source records attributed to H H Hansen.
[Metastatic spinal cord compression in patients with lung cancer].
Metastatic spinal cord compression (MSCC) is a disabling complication to cancer for which the optimal treatment of choice is not settled. An analysis was performed in patients with MSCC secondary to lung cancer in order to elucidate clinical symptoms and treatment results according to regression of neurological deficits and survival. The total series consisted of 102 retrospectively evaluated patients referred for treatment, in the Eastern part of Denmark in the period 1979-1988. Patients included 40% cases with Small Cell Carcinoma (SCLC), Adeno-carcinoma (ACL) (26%), Squamous Cell Carcinoma (SQLC) (18%) and Large Cell Carcinoma (LCC) (9%). Symptoms, clinical presentations and therapeutic results are described. The outcome of treatment depended fundamentally on the patient's neurological condition at the time of the diagnosis. All patients with SCLC who were able to walk at the time of MSCC remained ambulatory while 15% of the non-ambulatory SCLC patients regained walking ability; in non-SCLC, 95% of patients retained walking ability while 22% regained the ability to walk. No major differences in the immediate outcome of treatment between the various histological types of lung cancer as to the different treatment modalities were observed, however, 82% of the patients with non-SCLC had benefit from treatment with laminectomy followed by radiotherapy compared with either laminectomy (47%) or radiotherapy (39%) alone (p = .03, Chi-square test). The group of patients treated with laminectomy followed by radiotherapy had a better survival (median value 3.5 months, range 0-132 months) than patients treated with either laminectomy (median value 1.5 months, range 0-32 months) or radiotherapy (median value 1 month, range 0-59 months) alone (p = .03, Log-Rank test). No significant difference was observed in survival between the various histological types of lung cancer (p = .18, Log-Rank test). Despite a short survival, early diagnosis and immediate treatment is crucial, since it may preserve the gait function in 97% of lung cancer patients developing malignant spinal cord compression.
Adult↗
[Small cell lung cancer].
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Carcinoma, Small Cell↗
Chromosome aberrations and pharmacokinetics in patients receiving tauromustine as either a single or a repeated dose.
Tauromustine (TCNU) is an exploratory drug that has demonstrated activity in various solid tumors. We examined chromosome aberrations and plasma levels of the drug in two groups of patients receiving either a single dose of 130 mg/m2 or 40 mg/m2 on 3 consecutive days. Peak plasma concentrations (mean +/- SD) were obtained at a similar time after both treatments, i.e., at 38 +/- 25, 32 +/- 24, 28 +/- 14, and 40 +/- 26 min after administration of 130 mg/m2 on day 1 and after that of 40 mg/m2 on days 1, 2, and 3, respectively. In addition, the cumulative area under the curve (AUC value) determined after administration of 40 mg/m2 x 3 was similar to that noted after treatment with a single dose of 130 mg/m2, i.e., 180 and 179 micrograms min ml-1, respectively. Both treatments induced chromosome aberrations (CAs) in peripheral blood lymphocytes. A dose-dependent increase in the number of CAs was found, with 40 mg/m2 producing 5.5% CAs and 130 mg/m2 yielding 20.9% CAs at 24 h after treatment. In addition, although the drug concentration declined to a level under the detection limit between the daily treatments, drug-induced chromosome damage was cumulative, with the 90-min values increasing from 4.8% on day 1 to 14.3% CAs on day 3. In individual patients, no correlation was found between CAs and kinetic parameters; however, the total mean CA yield was in agreement with the total drug exposure (CAs, 14.3% and 14.6%, AUC 180 +/- 62.8 and 179 +/- 115 micrograms min ml-1, respectively.
Antineoplastic Agents↗
Small cell lung cancer: biological and therapeutic aspects.
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Adult↗
More power to trials for non-small-cell lung cancer.
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Carcinoma, Non-Small-Cell Lung↗
Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up.
PURPOSE: The introduction of platinum compounds and epipodophyllotoxins in combination with vincristine as induction chemotherapy in small-cell lung cancer (SCLC) was investigated in order to: (1) compare the efficacy of cisplatin with that of carboplatin in combination with teniposide and vincristine as inducers of remission over three cycles; (2) compare the toxicity pattern of carboplatin and of cisplatin when given in combination regimens; and (3) compare a chemotherapeutic regimen consisting of three alternating combinations with that of regimens consisting of four alternating combinations. PATIENTS AND METHODS: From November 1985 to September 1991, 484 consecutive, previously untreated patients with SCLC, performance status 0-4, entered a three armed randomized trial with three cycles of cisplatin (arm I) or carboplatin (arm II) in combination with teniposide and vincristine alternating with three treatment blocks of cyclophosphamide, etoposide, lomustine and vincristine (block A), doxorubicin and vincristine (block B) and cisplatin, hexamethylmelamine and vindesine (block C) versus alternating treatment with block A, B and C (arm III). RESULTS: No difference in efficacy or toxicity was found between cisplatin and carboplatin at the present dosages. Induction chemotherapy with teniposide plus cisplatin or carboplatin did not result in higher complete response rates (objective response rates 63%, 72% and 65%, respectively) or in significantly greater toxicity, but overall survival was superior compared with the arm III (log-rank test, P = 0.02). The median survival difference was 7 weeks, and two year survival 15% versus 9%. The Cox regression analysis identified the arm III, poor performance status and elevated LDH as factors with statistically significant negative impact on survival. CONCLUSION: Cisplatin and carboplatin produced similar response and survival rates and similar toxicity. Induction with platinum and epipodophyllotoxins did not improve objective response rates, but significantly improved survival without increasing the toxicity.
Adult↗
Thrombolytic therapy in diabetic patients with acute myocardial infarction.
OBJECTIVE: To compare the frequency of thrombolytic therapy in diabetic and nondiabetic patients with acute myocardial infarction (MI) and to examine why some diabetic patients do not receive thrombolytic therapy. RESEARCH DESIGN AND METHODS: Retrospective study of all diabetic patients with acute MI admitted to the coronary care unit of Aalborg Hospital within a 3-year period. RESULTS: Only 35% (43 of 123) of patients with diabetes compared with 47% (404 of 856) of patients without diabetes received thrombolytic therapy (P < 0.002). There was no difference in the percentage of patients thrombolyzed among patients admitted to the hospital within 12 h after onset of symptoms. Of diabetic patients who were not thrombolyzed, 60% (48 of 80) arrived at the hospital later than 12 h after onset of symptoms. Among patients who arrived late, 63% (35 of 56) had Q wave infarction and 84% (47 of 56) had symptoms typical of acute MI. Mortality was 29% (16 of 56) in this group. Only one patient did not receive thrombolytic therapy due to diabetic retinopathy. CONCLUSIONS: Significantly fewer diabetic patients received thrombolytic therapy compared with patients without diabetes. The main reason diabetic patients did not receive thrombolytic therapy was late arrival to the hospital.
Aged↗
Lung cancer.
In small cell lung cancer, combination chemotherapy including platinum compounds (cisplatin and carboplatin) and the podophyllotoxins (teniposide and etoposide) continues to be the backbone of therapy. Complete plus partial responses to combination chemotherapy occur in 80-90% of all patients. Median survival is at present 11-17 months depending on the initial tumour stage. Overall 5-year survival is approximately 5%. The duration of treatment has been shortened to 5-6 months. The results of the use of hematopoietic growth factors have hitherto been disappointing with respect to survival, while a definite effect on the degree and number of infections has been documented, when aggressive chemotherapy is administered. For epidermoid-, adenoid- and large cell carcinoma, results are emerging indicating that preoperative and preirradiatory chemotherapy in stage IIIa non-small cell lung cancer might have a substantial role in the overall management based on results from phase III trials. The studies are, however, rather modest in number and longer follow-up is necessary before recommendations for general use can be made. For patients with advanced non-small cell lung cancer (stage IIIb and IV), meta-analyses have yielded a small survival benefit (6 weeks) in favour of patients receiving chemotherapy vs. best supportive care. The treatment of this type of NSCLC should, however, still be considered to be experimental in order to define new innovative treatments. No improvement of the therapy of mesotheliomas has been reported.
Carcinoma, Non-Small-Cell Lung↗
Prophylactic cranial irradiation in small cell lung cancer--an update.
The role of prophylactic cranial irradiation (PCI) in the management of patients with small cell lung cancer is reviewed, with emphasis on 11 randomised trials. Several interpretive and methodological problems related to PCI investigations are identified, and it is argued that given the current data PCI should be considered as an optional treatment component in CR patients, that these authors do not recommend, while other investigators do.
Brain Neoplasms↗
Is there a role for chemotherapy of non-small cell lung cancer?
This paper reviews the results of individual studies and meta-analyses of chemotherapy of non-small cell lung cancer. The published results from studies of chemotherapy as part of a combined modality therapy which have been carried out in the last decade are conflicting. Some show a statistically superior survival for the group receiving chemotherapy compared with a best supportive care group, while the others show no advantage. The differences, however, are small. Meta-analysis of data from published randomized trials has been used by some authors to assess combination chemotherapy compared to supportive or palliative treatment of patients of non-resectable non-small cell lung cancer. In some of the randomized trials and meta-analyses results, a statistically significant effect on survival parameters following chemotherapy against non-small cell lung cancer is shown. The clinical significance of these observations is questionable and the results from larger ongoing trials must be awaited before chemotherapy is used routinely in the treatment of advanced NSCLC.
Carcinoma, Non-Small-Cell Lung↗
Evaluation of the optimal duration of chemotherapy in phase II trials for inoperable non-small-cell lung cancer (NSCLC).
PURPOSE: To determine the optimal duration of chemotherapy in phase II trials for patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The time from start of treatment until achievement of response according to WHO criteria was determined retrospectively in 8 phase II trials. RESULTS: Response to chemotherapy consisting of 4 complete and 39 partial remissions was registered in 43 of 333 patients. The median time from treatment start to response was 54 days. On day 84 on-study, 35 of the responding patients (81%) had achieved the response. Forty-three responses (98%) had occurred by day 168 and only one patient (2%) accomplished a response after 168 days of treatment. The responses had a median duration of 151 days (range 28-1559 days). CONCLUSIONS: The data indicate that patients with NSCLC included in phase II trials who have not yet achieved a response to chemotherapy after 168 days on study have a low likelihood (2%) of a subsequent response. Hence, treatment cessation at this point should be considered for non-responding patients. Continuation of treatment from day 84 to day 168 resulted in response in only 7 patients out of the total of 43 responses noted (16%). Thus, the toxic effects of the chemotherapy in addition to the inconvenience of hospital visits renders it questionable whether it is worthwhile to continue treatment in patients with inoperable non-small-cell lung cancer beyond day 84 in the absence of response.
Adult↗
Brain metastases in small-cell lung cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease.
The first clinical case of a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was presented by Schwartz et al. in 1957 (Am J Med 1957; 23: 529-42), describing two patients with lung cancer who developed hyponatraemia associated with continued urinary sodium loss. They postulated that the tumours led to the inappropriate release of antidiuretic hormone (ADH), later discovered to consist of arginine-vasopressin (AVP). This suggestion was later confirmed in several studies. The clinical description of the syndrome has changed little since the original observation, and the cardinal findings of SIADH are as follows: (i) hyponatraemia with corresponding hypo-osmolality of the serum and extracellular fluid, (ii) continued renal excretion of sodium. (iii) absence of clinical evidence of fluid volume depletion, (iv) osmolality of the urine greater than that appropriate for the concomitant osmolality of the plasma, i.e. urine less than maximal diluted, and (v) normal function of kidneys, suprarenal glands and thyroid glands. Measurement of AVP in plasma is not a part of the definition of SIADH. SIADH may be caused by a variety of malignant tumours, but may also be caused by various other conditions, such as disorders involving the central nervous system, intrathoratic disorders such as infections, positive pressure ventilation and conditions with decrease in left atrial pressure. Also, a large number of pharmaceutical agents have been shown to produce SIADH, including a number of cytotoxic drugs such as vincristine, vinblastine, cisplatin, cyclophosphamide, and melphalan. A broad spectrum of malignant tumours has been reported to cause SIADH; however, most of these observations have been in case reports including very few patients. This includes a number of primary brain tumours, haematologic malignancies, intrathoracic non-pulmonary cancers, skin tumours, gastrointestinal cancers, gynaecological cancer, breast-and prostatic cancer, and sarcomas. Larger series of patients have revealed that SIADH occurs in 3% of patients with head and neck cancer (47 cases out of 1696 patients), in 0.7% of patients with non-small-cell lung cancer (three cases out of 427 patients), and in 15% of cases of small-cell lung cancer (214 cases out of 1473 patients). The optimal therapy for SIADH is to treat the underlying malignant disease. If this is not possible, or if the disease has become refractory, other treatment methods are available such as water restriction, demeclocycline therapy, or, in severe cases, infusion of hypertonic saline together with furosemide during careful monitoring.
Humans↗
Long-term survival in small-cell lung cancer: posttreatment characteristics in patients surviving 5 to 18+ years--an analysis of 1,714 consecutive patients.
PURPOSE: To describe in patients with small-cell lung cancer (SCLC) the characteristics of those who survive for > or = 5 years, to identify long-term prognostic factors, to analyze survival data of 5-year survivors, and to study 10-year survival in patients entered before 1981. PATIENTS AND METHODS: A total of 1,714 unselected patients with SCLC were treated with combination chemotherapy in nine consecutive clinical trials from 1973 to 1991. All medical records were reviewed and follow-up data obtained to analyze and compare pretreatment and posttreatment characteristics. RESULTS: Sixty patients survived longer than 5 years. Late relapses occurred in 15.0% of 5-year survivors and secondary malignancies in 20.0%. Twenty-six patients are still alive and disease-free 5 to 18 years (median, 9.5 years) from initiation of treatment. Extensive-stage disease, performance status (PS) more than 2, liver and bone marrow metastases, and elevated lactate dehydrogenase (LDH) and alkaline phosphatase levels were all negative prognostic factors. The 5-year survival rate was 3.5% (limited-stage disease, 4.8%; extensive-stage disease, 2.3%), and the 10-year survival rate was 1.8% (limited-stage disease, 2.5%; extensive-stage disease, 1.2%). CONCLUSION: Long-term survival can be achieved for both stages of SCLC, but without any change in survival rates over the last decade. Long-term survivors continuously seem to have considerable mortality due to late relapses and secondary malignancies, especially tobacco-related cancers and other tobacco-related diseases.
Alkaline Phosphatase↗
Calcium in patients on hemodialysis.
Analyzing 415 measurements from 33 patients on chronic maintenance hemodialysis we confirm that 50% of total calcium in the range 1.59 to 3.33 mmol/l gives a valuable approximation to ionized calcium in the range 0.79 to 1.62 mmol/l. However, a small but significant effect of albumin and phosphate on ionized calcium can also be demonstrated. Conventional albumin correction of total calcium using the formula: total calcium + (43 g/l-Albumin g/l).0.017 mmol/g is of poor value in these patients on maintenance hemodialysis.
Calcium↗
Ultradian variation in serum phosphate concentration in patients on haemodialysis.
To study how much the serum phosphate concentration could vary on the day before scheduled dialysis we obtained 24-37 timed measurements during 24 h in nine patients on maintenance haemodialysis. During the observation there was an increase in serum phosphate concentration of 0.239 +/- 0.022, P < 0.01). Surprisingly six of the nine patients exhibited nine statistically and clinically significant nadirs with decrements of 0.21 +/- 0.04 mmol/l against an intra-assay standard deviation of about 0.05 mmol/l. Five of the nadirs occurred at 11.40-14.50, mean 12.59, and three at 19.00-21.30, mean 20.00. We found no coinciding changes in the serum calcium concentration. These findings indicate that serum phosphate concentrations do not always reflect phosphorus balance or intake.
Activity Cycles↗
Prognostic impact of urokinase, urokinase receptor, and type 1 plasminogen activator inhibitor in squamous and large cell lung cancer tissue.
We have studied the prognostic value of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and type 1 plasminogen activator inhibitor (PAI-1) in tumor extracts from 84 patients with squamous cell lung carcinoma and 38 patients with large cell lung carcinoma, measuring each molecule with sandwich enzyme-linked immunosorbent assays. High uPAR levels were significantly associated with short overall survival in patients with squamous cell lung carcinomas when the median value was used as a cutoff point (P = 0.038), while no statistically significant prognostic impact of uPA and PAI-1 levels was found in this group of patients. The combination of high uPAR and high PAI-1 levels did, however, have a particular significant association with short overall survival (P = 0.008). None of the 3 components was found to have a statistically significant prognostic impact in the group of 38 large cell lung cancer patients. There was a positive correlation between uPAR and PAI-1 levels in both groups and between uPA and uPAR levels in the large cell carcinoma patients. In a multivariate analysis, high uPAR was found to be an independent prognostic variable in squamous cell carcinoma patients, with a relative risk of 2.1 (95% confidence interval, 1.1-4.0) and tumor size the only other significant prognostic parameter. These data suggest that uPAR is an important prognostic factor in squamous cell lung carcinoma. In addition to the potential direct clinical usefulness, this information could be helpful in understanding the biology of this disease and developing new therapeutic approaches.
Aged↗