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H H Hansen

Publications and source records attributed to H H Hansen.

At least 145 records · Page 8Linked to original sources
PubMed1990

Second-line chemotherapy in small cell lung cancer.

The literature on second-line chemotherapy in small cell lung cancer (SCLC) for the period 1979-1989 is reviewed. The reports consisted mainly of Phase II type studies and comprised a total of 987 patients with relatively few patients per study. The information was frequently incomplete with regard to duration of response on first-line chemotherapy, length of any drug-free interval and duration of response on second-line chemotherapy. The overall second-line response rate was 30%, but only 5% were complete responses (CR). The response rates obtained by the combination of cisplatinum (P) and VP-16 (E) or reinduction therapy were 45% and 64% (medians), respectively. These rates were superior to regimens consisting of supposedly non-cross-resistant agents. With P and E not given in combination, the response rates were less than 20%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A randomized study of sequential versus alternating combination chemotherapy in advanced ovarian carcinoma.

The concept of using either alternating or sequential combination chemotherapy with non-cross-resistant combinations was tested in a randomized trial including 301 previously untreated patients with advanced epithelial ovarian carcinoma. The sequential schedule consisted of CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) followed by PH (cisplatin, hexamethylmelamine) in nonresponders, CAF- greater than PH (n = 157), and the alternating regimen consisted of CAF/PH (n = 144). With a median observation time of 54 months, no statistically significant differences were found between the pathologically complete response (PCR) rates of 17% and 16%, respectively, nor were there any statistical differences in median disease-free survival for PCR patients (CAF- greater than PH 34+ months and CAF/PH 26+ months), in overall survival (28 and 24 months, respectively), or in time to treatment failure (10 and 11 months). The overall estimated cure rate was 13%. An equal degree of myelosuppression was seen with the two regimens, whereas neuro- and nephrotoxicity were more pronounced when PH was given sequentially to CAF than with the alternating schedule. We conclude that the sequential and the alternated use of doxorubicin- and platinum-based regimens yield equivalent results and that other approaches should be investigated to improve treatment effects.

Adult↗
PubMed1990

Treatment of malignant germ cell tumors.

In an unselected group of 278 patients with germ cell tumors, disease-free status was obtained in 97% by a treatment program including a surveillance-only strategy for stage I testicular cancer, and low-or high-dose cisplatinum-etoposide treatment for patients with more extensive disease. The overall follow-up period was a median of 40 months (range 20-62 months). At present 100% of patients with stage I disease, 91% with stage II disease, 86% with stage III disease, 75% with extragonadal germ cell tumors, and 3 of 3 patients with germ cell tumors in the ovary are alive and without disease. Among 36 patients treated with high-dose cisplatinum and etoposide there were six toxic deaths, four of them in patients with residual malignant disease. Three patients died of progressive disease. There were no toxic deaths among 54 patients with disseminated disease but without poor prognostic features who were treated with low-dose cisplatinum-etoposide; six of these patients died of progressive disease. It is concluded: 1) that surveillance is a feasible and reasonable strategy for patients with stage I disease; 2) that excellent survival results can be achieved with standard-dose cisplatinum-etoposide in patients with disseminated disease and a favorable prognostic profile; and 3) that disease-free status can be obtained in nearly all patients with poor prognostic features at the expense of significant toxicity. Standardized criteria for selection of patients with poor prognoses are needed. Randomized trials should be carried out to define the role of high-intensity treatment and, finally, measures to decrease or prevent serious toxicity should be explored.

Adolescent↗
PubMed1990

TCNU in adenocarcinoma of the lung: a phase II study with divided doses.

TCNU, a new water soluble nitrosourea, has in preclinical studies shown higher activity when given as divided doses compared with one day single treatment. Accordingly, 38 consecutive patients with non-resectable adenocarcinoma of the lung received TCNU 40 mg/m2 p.o. daily for three days every 4 weeks. The response rate among 37 evaluable patients was 14%, median response duration was 17 weeks (range 5-57+ weeks) and median survival 22 weeks (range 3-96+ weeks). Hematologic toxicity was pronounced, especially thrombocytopenia, and 57% of the patients had WHO grade 3 or 4 WBC or platelet count. Overall, dose reduction or delay of treatment due to hematologic toxicity was necessary in 66% of the patients. This, together with the limited activity, renders TCNU in the present dose and schedule unsuitable for further investigations in this disease entity.

Adenocarcinoma↗
PubMed1990

Combined high-dose carboplatin and cisplatin, and ifosfamide in previously untreated ovarian cancer patients with residual disease.

Carboplatin 200 mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3, ifosfamide 1,500 mg/m2 days 1 to 3, and mesna 900 mg/m2 days 1 to 3 every 4 weeks for six cycles were given to 37 previously untreated ovarian cancer patients with residual disease after the primary laparotomy. The median observation time was 17+ months (range, 9+ to 24+ months). Of all the patients, 81% had primary residual disease larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 36 assessable patients was 58%, PCR was 42%. Of the PCR patients, 53% had primary residual tumor larger than 5 cm. The substantial hematologic toxicity was manageable, but also the main reason for dose modifications. During treatment, 92% and 100% of the patients developed WBC and platelet nadir values corresponding to World Health Organization (WHO) grades 3 to 4. Dose-limiting encephalopathy, nephro- and neurotoxicity each occurred in 6% of the patients. The high PCR rate warrants further investigations of combined high-dose platinum and ifosfamide.

Adult↗
PubMed1990

Lung cancer.

Explore the source record for details and available documents.

Adenocarcinoma↗
PubMed1990

Food-stimulated cholescintigraphy as a supplement to ERC in patients with suspected bile flow obstruction. A preliminary study.

Cholescintigraphy after food stimulation was carried out in 40 patients (13 patients with biliary enteric bypass, 14 patients with bile duct stenosis, demonstrated by ERC, 5 patients with endoprothesis and 8 patients with clinically suspected post-cholecystectomy syndrome. Biliary-bowel transit time of one hour or less was considered to be normal. In patients with biliary enteric bypass 11 had a normal transit time; however, one with a concomitant anastomotic leakage, and 2 patients had prolonged transit time and a significant obstruction by the anastomosis. All 14 patients with demonstrated biliary stricture had normal transit time. In 5 patients with endoprothesis, 2 had prolonged transit time in spite of patent endoprothesis. Finally, in the 8 patients with suspected post-cholecystectomy syndrome, 4 had normal sphincter of Oddi manometry and normal transit time, and 4 had abnormal sphincter of Oddi manometry, but only one with prolonged transit time. It is concluded that in patients with biliary enteric bypass (hepatico-jejunostomia) or biliary strictures a biliary-bowel transit time of one hour will be discriminatory between normal and abnormal conditions. This is in contrast to patients with endoprothesis and suspected sphincter of Oddi dysmotility, where a transit time of one hour only will have limited predictive value.

Adult↗
PubMed1990

Spect bone scintigraphy in assessment of cranial Paget's disease.

Single photon emission computed tomography (SPECT) bone scintigraphy was used in the assessment of Paget's disease in 3 patients with skull involvement. In comparison with conventional scintigraphy, SPECT improved the three-dimensional perception and made precise outlining of involved bones possible. The radionuclide uptake in lesions expressed as counts per pixel was 1.5 to 10 times that of normal bones. Routine use of SPECT in cranial Paget's disease for staging and monitoring the effect of treatment is proposed.

Aged↗
PubMed1989

Reduced variation in the clonogenic assay obtained by standardization of the cell culture conditions prior to drug testing on human small cell lung cancer cell lines.

An advantage of established tumor cell lines compared to fresh human tumor specimens used in sensitivity assessments is the possibility of repeated experiments. Ultimately a database of sensitivity profiles on a panel of cell lines can be made and the sensitivity to new drugs compared with historical data. A prerequisite of this strategy is a minimal interexperimental variation. The sensitivity of eight human small cell lung cancer cell lines to adriamycin, daunomycin, aclacinomycin A, and mitoxantrone was tested in the clonogenic assay. A covariation in the sensitivity to the drugs emphasized the importance of simultaneous drug testing on the same batch of cells. On one cell line (NCI-N592) the interexperimental variation was further evaluated and a significant correlation was found between preexposure culture conditions, size of S-phase, and sensitivity to adriamycin, daunomycin, and mitoxantrone. Rigorous standardization of the growth conditions prior to clonogenic assay reduced the variation in the sensitivity to adriamycin from a factor of five to only 10-15%. It is concluded that simultaneous experiments on the same batch of cells in drug comparisons should be used if possible. Specification and standardization of culture conditions are necessary in the comparison of drugs tested in different experiments. Inclusion of the same reference drug in all experiments may further increase the validity of comparisons in different experiments.

Carcinoma, Small Cell↗
PubMed1989

Tallysomycin S10b--a phase I trial.

Tallysomycin S10b is a new bleomycin analogue. In animal studies it has shown the same degree of antineoplastic activity as bleomycin; however in contrast to that of bleomycin, its dose-limiting effect in animal systems is renal toxicity and its pulmonary toxicity is less pronounced. A total of 16 patients received tallysomycin S10b at three exploratory levels: 3 patients were given a dose of 1.25 mg/m2, 9 received 2.5 mg/m2 and 4 were given 5 mg/m2 as i.v. bolus injections twice weekly. Before treatment and every 3 weeks, plain chest X-rays, pulmonary function tests, renography and 51Cr-EDTA clearance were carried out. No renal toxicity was found in any of the treatment groups. In the first two groups no changes in chest X-rays were observed during treatment, whereas in the third group a decrease in single-breath carbon monoxide diffusion capacity (DLCO) was seen in one patient until the treatment was discontinued. Two of four patients receiving 5 mg/m2 developed interstitial pneumonitis at total doses of 104 and 160 mg, respectively. During the trial no haematologic or hepatic changes occurred due to the drug. The frequency of occurrence of skin changes, stomatitis and fever increased with the cumulative dose of tallysomycin S10b, and these side effects were similar to those seen with bleomycin. No tumor regression was seen during the trial. In contrast to the findings in previous animal studies, we found that the dose-limiting effect was pulmonary and not renal toxicity. The recommended dose for further phase II trials is 2.5 mg/m2 twice weekly, with careful monitoring of the pulmonary function.

Adult↗
PubMed1989

Pharmacokinetics of tauromustine in cancer patients. Phase I studies.

The pharmacokinetic properties of tauromustine (TCNU) were studied in 31 cancer patients who participated in phase I trials. The patients received single oral doses of tauromustine in the range of 20-170 mg/m2. Plasma samples were taken over 24 h after administration and analysed for tauromustine by reversed-phase liquid chromatography. Parent TCNU could be demonstrated in the plasma of all patients. Its absorption was rapid (tmax = 38 +/- 22 min), the half-life was 57 +/- 22 min (mean +/- SD), and maximal concentration (Cmax) and AUC values were linearly related to the dose level. Thus, our study does not indicate dose-dependent pharmacokinetics for the drug in the range of 20-170 mg/m2. Thrombocytopenia was the dose-limiting toxicity of TCNU; the reduction of platelet counts appeared to be linearly related to the log dose and Cmax and AUC values. TCNU appears to exhibit pharmacokinetic properties that are different from those of other nitrosoureas, which might be important for the clinical effect of the drug.

Antineoplastic Agents↗
PubMed1989

Kidney function in newly diagnosed type 2 (non-insulin-dependent) diabetic patients, before and during treatment.

Glomerular filtration rate, kidney volume, and urinary albumin excretion rate were studied in otherwise healthy newly diagnosed Type 2 (non-insulin-dependent) diabetic patients, untreated at diagnosis, after short-term treatment and after 3 months treatment. In 10 patients (Group A) glomerular filtration rate (measured by the plasma clearance of 51-Cr-EDTA) decreased from the time of diagnosis 106.2 +/- 14.6 ml.min-1.1.73 m2(-1) (mean +/- SD) to 95.9 +/- 13.7 ml.min-1.1.73 m2(-1) after 3 months treatment (p = 0.049). At the same time, mean plasma glucose was reduced from 13.3 +/- 3.2 mmol/l to 6.5 +/- 1.1 mmol/l. The fall in mean plasma glucose was correlated to the reduction in glomerular filtration rate, r = 0.76, p = 0.011. Kidney volume as measured by ultrasonic scanning was reduced from 264.0 +/- 33.7 ml/1.73 m2 to 210.8 +/- 23.8 ml/1.73 m2 (p less than 0.005). The relative decline in urinary albumin excretion rate was correlated to the fall in glomerular filtration rate, r = 0.69, p = 0.026. In 15 patients (Group B) 24-h urine collections were made during 9.5 +/- 3.2 days, urinary albumin excretion rate fell from the first to the last day in hospital from 14.0 x/divided by 3.0 micrograms/min (geometric mean x /divided by tolerance factor) to 7.0 x/divided by 2.7 micrograms/min p = 0.015. The relative decline was correlated to the change in mean plasma glucose, r = 0.65, p = 0.032. Thus, kidney function in Type 2 diabetic patients is influenced by metabolic control, although to a lesser extent than is seen in Type 1 (insulin-dependent) diabetic patients with comparable glycaemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Hydronephrosis in advanced ovarian carcinoma.

In a consecutive series of 232 patients with ovarian carcinoma, (FIGO IIB-IV), receiving combination chemotherapy, 52 patients (22%) presented with (early, 69%) or developed (late, 31%) hydronephrosis diagnosed by intravenous pyelography or abdominal ultrasound scan. Unilateral hydronephrosis was seen in 77%, bilateral in 23%. Patients with hydronephrosis were characterized by stage IIIB-IV (67%), and primary residual tumor size greater than 2 cm (81%). Nine patients (17%) developed concomittantly impaired renal function diagnosed by a rise in se-creatinine and/or a decrease in 51Cr-EDTA clearance. No difference in survival was seen in patients with early or late hydronephrosis, nor with uni- or bilateral hydronephrosis, but patients with hydronephrosis at the start of chemotherapy lived significantly shorter than those without hydronephrosis, P less than .05. In conclusion, hydronephrosis is a common complication to advanced ovarian carcinoma, and the presence of this complication at the start of chemotherapy has a negative impact on survival.

Adult↗
PubMed1989

Neuron specific enolase, carcinoembryonic antigen and lactate dehydrogenase as indicators of disease activity in small cell lung cancer.

The clinical value of the three serum biomarkers neuron specific enolase (NSE), carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) were evaluated prospectively in 86 patients with small cell lung cancer (SCLC) entered into randomized clinical trials. The patients were monitored clinically very closely and biomarkers were measured before each course of chemotherapy. The correlation between disease extent and biomarker was significant for both NSE (2P: 0.001) and LDH (2P:0.05). Of those two biomarkers NSE was the most sensitive and was raised in 75% of all patients at diagnosis, in 67% of patients with limited disease, and in 86% of patients with extensive disease. All patients with three or more sites involved presented raised serum NSE levels but there was no significant correlation between definite number or specific sites known to have metastatic disease. There was a tendency towards a higher serum CEA level in extensive disease than in local disease. Only half the patients with metastatic disease had elevated (greater than 5.0 ng/ml) levels of CEA, and values above 50.0 ng/ml were unusual. In patients initially seropositive for NSE a close correlation was found during follow up between serum NSE and response (98%) or progressive systemic disease (100%). During a major response, either complete or partial, serum NSE showed minor fluctuations (mean 8 ng/ml, S.D. 1.79, range 4.6-12.1). At present serum NSE seem to be the most sensitive and valuable biomarker in the management of SCLC, while the gain by adding CEA is small. Furthermore, NSE may be a useful tool in the estimation of disease extent and response to treatment in patients in whom clinical or radiological evaluation is difficult.

Adult↗
PubMed1989

A phase I clinical and pharmacokinetic study of Brequinar sodium, DUP 785 (NSC 368390), using a weekly and a biweekly schedule.

Brequinar, DUP 785, is a substituted 4-quinoline carboxylic acid derivative which in preclinical studies has shown broad antitumor activity. It is a novel antimetabolite blocking pyrimidine nucleotide synthesis. In a clinical phase I study, 83 patients were treated on a weekly schedule and 18 patients on a biweekly schedule. The drug was given intravenously as a short infusion. Three patients were entered on each dose level from a starting dose of 6 mg/m2 up to 2600 mg/m2 weekly. The dose ranges on a biweekly schedule were 500-850 mg/m2. There was no dose escalation in individual patients. Pharmacokinetic studies were performed in 19 patients on a weekly schedule and in two patients on a biweekly schedule. A biphasic decay in plasma was observed with a median half life of 10 h (5.1-23.4). The main dose-limiting toxicity was thrombocytopenia. Of non-hematologic side-effects, stomatitis/mucositis occurred frequently. Skin eruptions occurred rarely, but were a major problem when found. All side-effects were fully reversible; there were no signs of cumulative toxicity. Antitumor activity was observed in one patient with a lung metastasis from a bladder cancer and in a patient with an unknown primary tumor. The recommended doses for phase II trials with DUP 785 are: 1500-2000 mg/m2 on a weekly schedule and 500-750 mg/m2 on a biweekly schedule dependent on status before treatment.

Adolescent↗
PubMed1989

In vitro and in vivo evaluation of the indoloquinone EO-9 (NSC 382 459) against human small cell carcinoma of the lung.

As the indoloquinone EO-9 has previously shown activity in several tumor model systems it was evaluated against four human small cell lung cancer cell lines by the clonogenic assay. In two cell lines (Nyh and Tol), exponential dose-response curves were achieved with both 1 h and continuous exposure, whereas no cell kill was obtained in the other two cell lines (69 and 592) when tested with 1 h incubation up to 0.25 microgram/ml. When the cells were exposed to drug in vitro, flow cytometric DNA analysis showed perturbations in the cell cycle distribution of the most sensitive cell line (Tol) at a lower EO-9 concentration than in the less sensitive cel line (592). This in vitro predicted difference in EO-9 sensitivity between two of the cell lines (592 and Tol) was confirmed when the cell lines were heterotransplanted to nude mice.

Animals↗
PubMed1989

Response to cytostatic treatment in inoperable adenocarcinoma of the lung: critical implications.

The prognostic factors for response to chemotherapy and the prognostic impact of response status on survival, relative to other prognostic variables, were evaluated among 53 responding (9 complete responses; 44 partial responses) and 165 non-responding patients with inoperable adenocarcinoma of the lung (ACL). Multiple logistic regression analysis, including 27 pretreatment variables, revealed that the only significant predictor of response was bidimensionally measurable disease parameter (P = 0.02), followed by brain metastases that were negatively correlated to response, although insignificantly (P = 0.10). Univariate landmark analyses among patients alive at 8, 12, 16 and 24 weeks showed a trend towards better survival for responders compared with non-responders, but did not reach a significant level at any time (P values 0.78, 0.57, 0.23 and 0.12, respectively). Death hazard ratios for responders to non-responders were 0.91, 0.89, 0.79 and 0.73. Multivariate regression analysis among patients alive at 16 weeks demonstrated a significant impact on survival for performance status, non-radical tumour resection, liver metastases and LDH, while the impact of response status in comparison was weak and insignificant. This reflects the unsatisfactory treatment results achieved in inoperable ACL, with the majority of responses being partial, and calls for improvement of the cytostatic treatment currently available.

Adenocarcinoma↗