Management of small-cell cancer of the lung.
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Carcinoma, Small Cell↗
Biomedical subjects
H H Hansen
Publications and source records attributed to H H Hansen.
Doxorubicin sensitivity pattern in a panel of small-cell lung-cancer cell lines: correlation to etoposide and vincristine sensitivity and inverse correlation to carmustine sensitivity.
The aim of our investigations is to evaluate whether the sensitivity patterns of small-cell lung-cancer (SCLC) cell lines in vitro can be used in evaluating new drugs and in selecting drugs for the optimization of combination therapy. In our attempts to obtain a panel of cell lines demonstrating differential patterns in sensitivity, we have developed three SCLC lines exhibiting different types of multidrug resistance (MDR). In the present investigations we compared the sensitivity patterns shown by five wild-type SCLC lines and three MDR lines in response to six different types of drugs: doxorubicin, cytarabine, carmustine, cisplatin, vincristine, and etoposide. In the wild-type SCLC cell lines, the range of variation in sensitivity to all drugs was within a factor of 10. Cell lines showing low sensitivity to doxorubicin also exhibited low sensitivity to etoposide and vincristine, and vice versa. In contrast, the pattern of sensitivity to carmustine was almost the opposite of that to doxorubicin. A tendency to an inverse relationship between doxorubicin and carmustine sensitivity was also observed when doxorubicin sensitivity was reduced in near stationary cells and in cells exposed to the metabolic inhibitor 2-deoxy-D-glucose. In agreement with the pattern observed for the wild-type lines, all of the MDR sublines demonstrated collateral sensitivity to carmustine. As to cytarabine, the wild-type lines expressed a sensitivity pattern similar to that shown in response to doxorubicin. Interestingly, the opposite pattern was found in the MDR lines, as all three demonstrated cytarabine hypersensitivity. The combination of alkylating agents and "MDR" drugs are of proven clinical benefit in the treatment of solid tumors, as is the combination of anthracycline and cytarabine in acute myeloid leukemia. The experimentally derived sensitivity data on cytarabine, alkylating agents, and MDR drugs (i.e., etoposide, doxorubicin, vincristine) thus resemble the clinical experience with these drugs, and we conclude that the use of a clonogenic assay on the described panel of SCLC cell lines can give valuable information for the selection of agents for combination therapy.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Serum neuron specific enolase (NSE) is a determinant of response duration in small cell lung cancer (SCLC).
Seventy-two consecutive patients were eligible for a study of clinical determinants of response and response duration in small cell lung cancer (SCLC). Pretreatment values of routine laboratory parameters, and three tumour markers: neuron specific enolase (NSE), carcinoembryonic antigen (CEA), and acidic glycoprotein (AGP) were measured. Descriptive clinical variables as performance status (PS), extent of disease, age and sex were also included in the study. All variables were analysed for influence on the type and duration of response. The complete remission probability was only related to pretreatment extent of disease. In a multivariate analysis (Cox) of response duration, only NSE and type of response had significant influence. Consequently, measurements of NSE before therapy will be useful in future clinical trials on SCLC especially in situations, where responding patients are submitted to specific treatment strategies.
Adult↗
Ways to a better treatment of small cell lung cancer--a commentary.
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Carcinoma, Small Cell↗
The impact of abdominal computerized tomography on the pretreatment staging and prognosis of small cell lung cancer.
One hundred six patients with small cell lung cancer (SCLC) were prospectively evaluated with regard to the prognostic impact of abdominal CT-scan in the pretreatment staging when compared to ultrasonography of the abdomen. Staging based on abdominal ultrasonography (US) plus bilateral bone marrow examinations gave as a result that 47 patients had extensive disease (ED) (44%). Seventeen patients with proven ED at time of referral were not included in this study. Abdominal CT-scan was performed in 76 of the 106 patients. Thirty patients of these 76 patients (39%) were classified as having ED after staging including US, but abdominal metastases were disclosed in another ten patients at the subsequent CT-scan. Liver metastases seen in two patients at ultrasonography were overlooked on the CT-scans. Median survival of the 36 patients classified as having limited disease (LD) after both procedures was 458 days, which was significantly better compared to 330 days for the ten patients with stage migration from LD to ED based on CT-scan, (p less than 0.05) and compared to 242 days in the 30 patients with ED demonstrated by both US and CT-scans (p less than 0.05). The prognostic impact of the CT-scan was further investigated in a multivariate analysis (Cox). Stage disease, performance status, LDH and alkaline phosphatase were significant prognostic factors in a proportional hazards model based on the original 106 patients. Patients in the best prognostic group were characterized by LD, good performance status (0-1) and normal LDH and alkaline phosphatase serum values. This group consisted of 22 patients (21%).(ABSTRACT TRUNCATED AT 250 WORDS)
Abdominal Neoplasms↗
Metastatic spinal cord compression secondary to lung cancer.
PURPOSE: Metastatic spinal cord compression (MSCC) is a disabling complication to cancer, the optimal treatment for which is not settled. An analysis was performed for all patients with MSCC secondary to lung cancer in East Denmark from 1979 to 1988. PATIENTS AND METHODS: The total series included 102 cases with small-cell carcinoma (SCLC; 40%), adenocarcinoma (ACL; 26%), squamous cell carcinoma (SQLC; 18%) and large-cell carcinoma (LCC; 9%). Symptoms, clinical presentations, and therapeutic results are described. RESULTS: The outcome of treatment depended fundamentally on the patient's neurologic condition at the time of the diagnosis. All patients with SCLC who were able to walk at the time of MSCC remained ambulatory, whereas 15% of the nonambulatory SCLC patients regained walking ability. In non-SCLC, 95% of patients continued to be able to walk, whereas 22% regained the ability to walk. No major differences in the immediate outcome of treatment between the various histologic types of lung cancer and the different treatment modalities were observed; however, 82% of the patients with non-SCLC benefited from treatment with laminectomy followed by radiotherapy (RT) compared with either laminectomy (47%) or RT (39%) alone (P = .03, chi 2 test). The group of patients who were treated with laminectomy followed by RT had a better survival (median value, 3.5; range, 0 to 132 months) than patients who were treated with either laminectomy (median value, 1.5; range, 0 to 32 months) or RT (median value, 1; range, 0 to 59 months) alone (P = .03, log-rank test). No significant difference was observed in survival between the various histologic types of lung cancer (P = .18, log-rank test). CONCLUSION: Despite a short survival, early diagnosis and immediate treatment is crucial because it may preserve the gait function in 97% of lung cancer patients who develop malignant spinal cord compression.
Adenocarcinoma↗
Systemic chemotherapy of brain metastases from small-cell lung cancer: a review.
PURPOSE: For decades the treatment of choice in small-cell lung cancer (SCLC) with brain metastases has been corticosteroids and radiotherapy (RT) because of a presumed lack of penetrance of cytostatic agents into parenchymatous brain metastases. In recent years, several reports have appeared on radiologic and clinical responses to systemic chemotherapy without additional RT in patients with metastatic SCLC in the brain. We reviewed the literature and focused on the methodologic aspects in comparison with RT data. DESIGN: We reviewed 12 patient series that included 116 patients and were published between 1981 and 1990. RESULTS: The overall brain response to chemotherapy without irradiation in patients with intracranial metastases at diagnosis was 76%, whereas the response rate of brain relapses was 43%. CONCLUSIONS: We conclude that intracranial metastases from SCLC seem to respond to chemotherapy as readily as other metastatic locations of SCLC do. Thus first-line cranial irradiation probably should be applied routinely only in cases of delayed brain metastases. Whether consolidating cranial RT should be given after a few courses of initial chemotherapy in SCLC patients with brain metastases at diagnosis is unclear and warrants a randomized evaluation.
Antineoplastic Combined Chemotherapy Protocols↗
Pressure and blood flow in pituitary adenomas measured during transsphenoidal surgery.
In 48 patients undergoing transsphenoidal surgery for pituitary adenoma, the intrasellar pressure was recorded during surgery. In 14 patients, adenoma blood flow was measured with the technique of local injection of 133xenon. Median intrasellar pressure was 30 mmHg (range 8-62), n = 48, and median adenoma blood flow was 8 ml/100 g/min (range 0-37), n = 14. In two patients, blood flow in the anterior pituitary gland was measured, and values of 26 and 22 ml/100 g/min were obtained. The finding that intrasellar pressure is above central venous and intracranial pressure suggests the possibility that the adenoma and the anterior pituitary gland are supplied not only with venous blood, but receive an additional arterial supply at a less than normal arterial pressure. In three cases perfusion pressures that caused arrest of adenoma blood flow were found, and these observations are discussed with reference to pituitary apoplexy.
Adenoma↗
Lung cancer.
In small cell lung cancer, combination chemotherapy including agents such as etoposide, teniposide, cisplatin, doxorubicin, vincristine and cyclophosphamide continues to be the backbone of therapy. Epipodophyllotoxin derivatives, together with cisplatin, are used increasingly as part of the initial therapy. Complete plus partial responses to combination chemotherapy still occur in 80-90% of all patients with a median duration of 9-11 months. Median survival in these studies is at present 11-16 months depending on the initial tumour stage. Deaths from small cell lung cancer continue to occur until 7 years after diagnosis, but rarely thereafter. At this point, overall survival is around 5% and include a small fraction of patients (1%) initially presenting with extensive disease. The optimum duration of treatment is still uncertain. For patients with extensive disease, the use of alternating chemotherapy has been shown in a couple of randomized studies to yield the best results, as judged by long-term survival. The results of several phase II studies stress the importance of dose scheduling of etoposide in small cell lung cancer, with continuous treatment of 5 days' duration or more being superior. The therapeutic results for epidermoid, adenoid, large cell carcinoma and mesothelioma are essentially unchanged. The treatment of patients with these types of lung cancer should continue to be considered experimental, since no standard chemotherapy has as yet been developed, neither when given as single modality nor in combination with surgery or radiotherapy. One single study comparing induction chemotherapy before irradiation vs irradiation alone has resulted in an improvement of median survival of 4 months and doubled the number of long-term survivors. Since three-fourths of the patients with locoregional disease will die within 3 years, further improvements in both systemic and local treatment are needed.
Antineoplastic Combined Chemotherapy Protocols↗
Teniposide in the treatment of small cell lung cancer: a review.
The epipodophyllotoxin derivatives teniposide and etoposide have been under clinical investigation for over 15 years. Although etoposide has been established as one of the most active compounds in the treatment of small cell lung cancer (SCLC), teniposide has received little attention. The results of seven phase II studies evaluating response rate and duration of response to teniposide in 10 previously treated and 102 untreated patients showed response rates of 21% and 58%, respectively. The most frequently used dosage schedule was 60 mg/m2 intravenously daily for 5 days every 3 weeks. The following are factors influencing the response rate and duration of response to teniposide: performance status; prior weight loss; prior chemotherapy exposure, including prior treatment with etoposide; stage; and effectiveness of prior chemotherapy, including time from last administration. Preliminary analyses from a study comparing the efficacy of teniposide with that of etoposide suggest that teniposide may be more effective in previously untreated patients with SCLC who are 70 years of age or older. The preliminary data, however, indicate that equivalent doses of teniposide cause more cases of leukopenia than etoposide. Before a final conclusion can be drawn, the results from an ongoing study using teniposide and etoposide at equitoxic doses must be evaluated.
Carcinoma, Small Cell↗
Combination therapy with carboplatin/cisplatin/ifosfamide/etoposide in ovarian cancer.
In 1987 a phase II study of combined high-dose platinum (carboplatin 300/mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3 q4wk) was carried out in 42 previously untreated ovarian cancer patients with residual disease. Since then, another phase II study of combined high-dose platinum and ifosfamide (1,500 mg/m2 days 1 to 3) has been carried out in 37 patients, while a third study of combined high-dose platinum and etoposide (70 mg/m2 intravenously days 1 to 5) is ongoing. Pathologic complete response (CR) and partial response (PR) rates in the first two studies were 62% in 37 evaluable patients, and 58% in 36 patients, 22% and 42% of whom were CRs, respectively. The preliminary results from the third study were: CR plus PR, 56%; CR, 24%. Hematologic toxicity was the dose-limiting factor in all three studies. Myelosuppression became substantial, but manageable, if another drug was added to the platinum combination. The percentage of patients experiencing World Health Organization grades 3 and 4 toxicity during treatment were: white blood cells 44%, 92%, and 79%; platelets 81%, 100%, and 95%, respectively, in studies I, II, and III. Nonhematologic toxicity was modest in all studies. Dose-limiting neurotoxicity occurred in 7%, 6%, and 5%; nephrotoxicity in 22%, 6%, and 11% of the patients. The percentage of patients receiving the stipulated doses of all study drugs in the sixth cycle was 31 in the first study compared with none in the second study. Combined high-dose platinum given either alone or in combination with ifosfamide or etoposide is highly active in ovarian carcinoma. However, further follow-up and a randomized trial are needed to establish the superiority of any one regimen.
Adult↗
[Calcitonin. II. Radioimmunological determination].
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Calcitonin↗
[Calcitonin. III. Use of serum calcitonin as a tumor marker in breast and pulmonary neoplasms].
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Adult↗
[Paravasal sclerotherapy: experimental study on the effect of sclerosing agents (author's transl)].
Sclerosing and side effects of three solutions mostly used for paravasal sclerotherapy were studied by subcutaneous injections in lower legs of rats. The results demonstrate that of the three examined sclerosing agents 5 p.c. phenol in almond oil has the lowest toxocity in tissue besides a sufficient production of collagen fibres.
Animals↗
Bone mineral content in osteogenesis imperfecta tarda and in otosclerosis.
In 22 patients with osteogenesis imperfecta and in 63 patients with otosclerosis the bone mineral content in peripheral bones was determined by photon absorptiometry. The bone mineral content proved significantly reduced in patients with osteogenesis imperfecta as compared with normals and with patients with otosclerosis. In the latter patients the bone mineral content was normal. These findings support the assumption that stapedial fixation in otosclerosis and in osteogenesis imperfecta is of different aetiology.
Adolescent↗
Fractional intestinal calcium absorption in epileptics on anticonvulsant therapy. Short-term effect of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol.
Fractional intestinal 47Ca calcium absorption (alpha) in 12 epileptic outpatients receiving chronic high-dose anticonvulsant therapy was reduced (p less than 0.05) compared to 12 matched normal controls. Six of the epileptics were treated orally with 0.5 microgram of 1,25-dihydroxycholecalciferol (1,25-DHCC) per day and six with 10 microgram of 25-hydroxycholecalciferol (25-HCC) per day for 10 days. The alpha was determined before and after treatment and compared with the effect of 0.5 microgram of 1,25-DHCC per day given for 10 days to 6 controls. An increase of the same order in alpha was found in all groups (p less than 0.05). No changes were observed in the serum levels of calcium, phosphorus, alkaline phosphatase or iPTH during treatment. Urinary calcium excretion was low in the epileptic patients and rose during treatment. The investigation demonstrates that the sensitivity of the intestine to 1,25-DHCC is normal in epileptic patients on anticonvulsant therapy and that 1,25-DHCC and 25-HCC in the given doses had an equal effect on the reduced intestinal calcium absorption.
Administration, Oral↗
Mineral content of skeletal bones in otosclerosis.
In 63 patients with otosclerosis confirmed by operation, the bone mineral content was determined by photon absorptiometry. The bone mineral content and bone mineral concentration were found to be normal, which lends support to the assumption that otosclerosis is a localized disease and not a manifestation of a generalized disorder of the skeletal system.
Absorption↗
Bilateral bone-marrow examinations in small-cell anaplastic carcinoma of the lung.
Bilateral bone-marrow examinations from the posterior iliac crests were routinely performed as a pretreatment staging procedure in 89 consecutive patients with small-cell anaplastic carcinoma of the lung. Bone-marrow involvement was found in 20 patients (22.5%), in 9 (10.1%) only on one side, and in 11 (12.4%) on both sides. Aspiration was found to be significantly superior to biopsy, being positive in 25 examinations as compared with 14 positive biopsies. Compared with unilateral bone-marrow examination the positive findings increased by approximately 30%. Bilateral bone-marrow examinations are recommended in patients in whom the detection of bone-marrow metastases will have therapeutic implications.
Biopsy, Needle↗