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Biomedical subjects

H H Hansen

Publications and source records attributed to H H Hansen.

At least 127 records · Page 7Linked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells: relationship to DNA integrity and topoisomerase II.

The effect of combinations of the anthracyclines aclarubicin and daunorubicin was investigated in a clonogenic assay using the human small cell lung cancer cell line OC-NYH and a multidrug-resistant (MDR) murine subline of Ehrlich ascites tumor (EHR2/DNR+). It was found that the cytotoxicity of daunorubicin in OC-NYH cells was antagonized by simultaneous exposure to nontoxic concentrations of aclarubicin. Coordinately, aclarubicin inhibited the formation of daunorubicin-induced protein-concealed DNA single-strand breaks and DNA-protein cross-links in OC-NYH cells when assayed by the alkaline elution technique. Aclarubicin had no influence on the accumulation of daunorubicin in these cells. In contrast, the accumulation of daunorubicin in EHR2/DNR+ cells was enhanced by more than 300% when the cells were simultaneously incubated with the MDR modulator verapamil, aclarubicin, or the two agents combined. Yet the cytotoxicity of daunorubicin was potentiated significantly only by verapamil. The increased cytotoxicity of daunorubicin in the presence of verapamil was completely antagonized when aclarubicin was used together with the MDR modulator. Finally, the effect of daunorubicin on the DNA cleavage activity of purified topoisomerase II in the presence and absence of aclarubicin was examined. It was found that daunorubicin stimulated DNA cleavage by topoisomerase II at specific DNA sites. The addition of aclarubicin completely inhibited the daunorubicin-induced stimulation of DNA cleavage. Taken together, these data indicate that aclarubicin-mediated inhibition of daunorubicin-induced cytotoxicity is due mainly to a drug interaction with the nuclear enzyme topoisomerase II. This antagonism at the nuclear level explains why aclarubicin is a poor modulator of daunorubicin resistance even though aclarubicin is able to increase the intracellular accumulation of daunorubicin in a MDR cell line.

Aclarubicin↗
PubMed1991

Phase II study of teniposide in adenocarcinoma of the lung.

A total of 26 evaluable patients with previously untreated, non-resectable adenocarcinoma of the lung were given 80 mg/m2 i.v. teniposide daily for 5 days every 3 weeks. Three partial responses (11%) were obtained that lasted for 12, 11 and 32 weeks, respectively. Leucopenia was the dose-limiting side effect, with WBC counts of less than 2 x 10(9)/l being observed in 42% of patients, resulting in one septic death. At the dose and schedule used in the present study, teniposide showed only limited activity in adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1991

Chemotherapy in malignant mesothelioma: a review.

This review of malignant mesothelioma focuses on the activity of single-agent and combination chemotherapy, a field in which research has thus far been rather unsystematic and sparse. Available results neither accede to any substantial drug activity nor justify the use of standard therapy. Furthermore, even when pooled most findings do not fulfil the basic criteria for a phase II trial. Prospective (multicenter) phase II trials are recommended for the identification of new agents that show antineoplastic activity in malignant mesothelioma. The use of computed tomography scans can assist in the prediction of the extent of disease both before and during treatment. Tumor-biological systems using mice xenografts or cell lines of human mesothelioma should be further developed so as to improve the screening of new agents exhibiting potential antineoplastic activity that is especially directed against mesothelioma.

Antineoplastic Agents↗
PubMed1991

Combination chemotherapy of limited-stage small-cell lung cancer. A controlled trial on 221 patients comparing two alternating regimens.

The outcome of two different alternating regimens of chemotherapy was investigated in a prospective controlled trial in limited-stage small-cell lung cancer (SCLC). Both regimens comprised cyclophosphamide, lomustine, vincristine, methotrexate, doxorubicin and etoposide administered in different schedules. The investigative regimen (B) included simultaneous administration of cyclophosphamide + lomustine alternating with cyclophosphamide + doxorubicin, and with doxorubicin + lomustine. The hypothetical superiority of this regimen was based on data from experimental animal tumors suggesting potentiated efficacy of the three specific combinations. A total of 234 patients were included, and 113 vs 108 patients were eligible. Median survival in both groups was 48 weeks (p = 0.89). Complete remissions were observed in 36/101 and in 42/99 patients evaluable for response. There was no significant difference in response duration. At restaging after 18 months of chemotherapy 27 patients (16%) and 22 patients (16%), respectively, were free of disease. Six patients, three in each arm, are still alive, 8+ to 10.5+ years after diagnosis. Scheduled doses of the six agents were the same in the two regimens except for a 30% reduction of every second dose of cyclophosphamide in regimen B. Nevertheless, regimen B resulted in significantly more leukopenic patients, septicemic episodes, and blood transfusions, and the dosage of etoposide was more often reduced in arm B than in arm A. The increased toxicity was not associated with improved treatment results.

Adult↗
PubMed1991

Prognostic impact of histologic demonstration of chromogranin A and neuron specific enolase in pulmonary adenocarcinoma.

One hundred-fourteen patients with inoperable adenocarcinoma of the lung (ACL) were evaluated by immunohistochemistry with monoclonal antibodies against Neuron Specific Enolase (NSE) and Chromogranin A (Chr A) in order to determine the frequency and prognostic impact of such antigen expression. All patients were previously untreated and received chemotherapy according to a prospective randomized trial. The tumors of 18 patients (16%) had more than 10% positive cells stained with anti-NSE, 59 (52%) had 1-10% positive cells and those of 37 patients (32%) contained no NSE-positive cells. The corresponding figures for Chr A were: 22 patients (19%), 51 patients (45%) and 41 patients (36%), respectively. Forty-four per cent of the patients with more than 10% positive NSE cells responded to chemotherapy (either complete or partial remissions) compared to 17% of the patients with fewer than 10% positive cells (p less than 0.025). The corresponding values for Chr A were 30% responders versus 19% responders (not statistically significant). The median survival for patients with more than 10%, 1-10% or no NSE-positive cells was 262 days, 231 days and 159 days, while, for Chr A it was 245 days, 200 days and 238 days, respectively. The survival curves for both NSE and Chr A according to the various levels of positivity were not significantly different. The presence of neuroendocrine marker in pulmonary adenocarcinoma seems to be associated with increased sensitivity to chemotherapy.

Adenocarcinoma↗
PubMed1991

Teniposide and etoposide in previously untreated small-cell lung cancer: a randomized study.

A randomized study comparing teniposide (VM-26) and etoposide (VP-16) was performed to investigate whether there are any differences in the activity and toxicity of these two analogs in small-cell lung cancer (SCLC). Only previously untreated patients with SCLC were included; 46 and 48 patients receiving VP-16 and VM-26, respectively, are assessable for response. There were no differences between the two groups with respect to extent of disease, median age, and performance status (PS). The initial doses were for both compounds 70 mg/m2 intravenously (IV) daily for 5 days every 3 weeks. After inclusion of 25 patients in the study, the doses were increased to 80 mg/m2 for VM-26 and 90 mg/m2 for VP-16 because of differences in toxicity. VM-26 caused more hematologic toxicity than VP-16 throughout the study. The overall responses (complete response [CR] plus partial response [PR]) were 65% for VP-16 and 71% for VM-26, with CR occurring in 24% and 23%, respectively, for the two compounds. Median survival was 8.5 months for VP-16-treated patients versus 11.3 months for VM-26-treated patients (P = .58). It is concluded that both VP-16 and VM-26 are highly active single agents in SCLC.

Aged↗
PubMed1991

Lung cancer.

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Adenocarcinoma↗
PubMed1990

Antagonistic effect of aclarubicin on the cytotoxicity of etoposide and 4'-(9-acridinylamino)methanesulfon-m-anisidide in human small cell lung cancer cell lines and on topoisomerase II-mediated DNA cleavage.

The effect of combinations of the anthracycline aclarubicin and the topoisomerase II targeting drugs 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyra noside) (VP-16) and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) was investigated in a clonogenic assay. The cytotoxicity of VP-16 was almost completely antagonized by preincubating cells with nontoxic concentrations of aclarubicin. The inhibition of cytotoxicity was not seen when the cells were exposed to aclarubicin after exposure to VP-16. The inhibition was significant over a wide range of aclarubicin concentrations (3 nM to 0.4 microM), above which the toxicity of aclarubicin became apparent. A similar effect was seen on the toxicity of m-AMSA. In contrast to aclarubicin, preincubation with Adriamycin did not antagonize the effect of VP-16. With purified topoisomerase II and naked DNA, aclarubicin did not stimulate the formation of cleavable complexes between topoisomerase II and DNA. Aclarubicin concentrations above 1 microM inhibited the baseline formation of cleavable complexes elicited with the enzyme alone. Low (1 to 10 nM) aclarubicin concentrations increased the formation of cleavable complexes obtained with VP-16 and m-AMSA; however, at aclarubicin concentrations above 1 microM an antagonistic effect was obtained. In cells, the m-AMSA- and VP-16-induced, protein-concealed DNA strand breaks were completely inhibitable by aclarubicin preincubation with no synergic dose levels. Our results suggest that aclarubicin inhibits topoisomerase II-mediated DNA cleavage. This inhibition could represent the mechanism of action of the drug and explain the lack of cross-resistance to the classical anthracyclines. The observed antagonism could have consequences for scheduling of aclarubicin with topoisomerase II-active anticancer drugs.

Aclarubicin↗
PubMed1990

Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation.

The epipodophyllotoxines VP-16 and VM-26 are chemically closely related. VM-26 has been found to be considerably more potent than VP-16 in vitro in a number of investigations. Although the drugs have been known for greater than 20 years, they have not been compared at clearly defined equitoxic doses on an optimal schedule in vivo and it has not been clarified as to whether a therapeutic difference exists between them. A prolonged schedule is optimal for both drugs; accordingly we determined the toxicity in mice using a 5-day schedule. The dose killing 10% of the mice (LD10) was 9.4 mg/kg daily (95% confidence limits, 7.4-11.8) for VP-16 and 3.4 (2.5-4.5) mg/kg daily for VM-26. In vitro, we found VM-26 to be 6-10 times more potent than VP-16 in a clonogenic assay on murine tumors P388 and L1210 leukemia and Ehrlich ascites. This pattern was also demonstrated in a multidrug-resistant subline of Ehrlich selected for resistance to daunorubicin (Ehrlich/DNR+), as it was 30 times less sensitive than Ehrlich cells to both VP-16 and VM-26. Using 90%, 45%, and 22% of the LD10 on the same murine tumors in vivo, we found that the effect of the two drugs was equal as evaluated by both the increase in life span and the number of cures. The drugs were also compared in nude mice inoculated with human small-cell lung cancer lines OC-TOL and CPH-SCCL-123; however, they were more toxic to the nude mice and only a limited therapeutic effect was observed. In conclusion, the complete cross-resistance between the two drugs suggests that they have an identical antineoplastic spectrum. VM-26 was more potent than VP-16 in vitro; however, this was not correlated to a therapeutic advantage for VM-26 over VP-16 in vivo.

Animals↗
PubMed1990

Scintigraphy with nanocolloid Tc 99m in patients with small cell lung cancer, with special reference to bone marrow and hepatic metastasis.

Nineteen patients with newly diagnosed small cell lung cancer (SCLC) were examined with a nanocolloid Tc-99m bone marrow whole body imaging (scintigraphy) in order to detect bone marrow metastasis. Bilateral bone marrow biopsy taken from the posterior iliac crest was used as a reference. The scintigraphy was considered abnormal if a focal lesion was present and/or if the bone marrow activity expanded to more than one-third of the proximal part of the extremities. In 3 of the 19 patients, microscopical bone marrow metastasis and cold spots (focal lesions) on the scintigram were present. An additional 9 patients had expansion of the activity. Eight patients showed scintigraphic focal lesions in the liver. SCLC metastasis was confirmed in 4 patients, while 1 patient had focal necroses. The results indicate that cold spots rather than expansion of activity with bone marrow scintigraphy detected bone marrow involvement of the disease in patients with SCLC.

Biopsy↗