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Biomedical subjects

O Klepp

Publications and source records attributed to O Klepp.

At least 19 recordsLinked to original sources

Treatment intention in hospitalized cancer patients in oncological wards in Norway: a national survey.

Clinicians often do not agree whether a treatment is given with a palliative or curative intent. A common clear definition does not exist. This study has assessed the usefulness of dividing the goal of treatment into three distinct categories: curative treatment; palliative, symptom preventive treatment; and palliative, symptom relieving treatment. In a cross-sectional study among all cancer centres in Norway, a total of 629 patients were included into the study. Of these patients, 60% received palliative treatment, with an equal distribution between symptom preventive and symptom relieving. The definitions were found easy to use by the physicians. It gave important information of differences between cancer diagnosis with respect to the number of patients receiving palliative treatment. In order to refine the classification system, the authors will, in future studies, include a fourth category, life prolonging treatment, which is located between curative and palliative treatment with respect to treatment intensity.

Cross-Sectional Studies

Phase II trial of anaxirone (TGU) in advanced colorectal cancer: an EORTC Early Clinical Trials Group (ECTG) study.

Anaxirone, a rationally synthesised triepoxide derivative, was given to 46 patients with metastatic colorectal cancer. Good risk patients received 800 mg/m2 as a rapid intravenous injection every 4 weeks, whereas poor risk patients received 650 mg/m2. Of 46 patients, 45 were evaluable for toxicity and 42 for efficacy analysis. There were 37/45 patients with poor risk, showing no difference in toxicity as compared to good risk patients. The major toxic effect was myelosuppression with 34% of all patients experiencing grade 3 or 4 leucopenia; thrombocytopenia was less frequent. Locoregional phlebitis occurred in 66% of the patients. There was no objective tumour response to anaxirone in 42 evaluable patients. Only 4 patients achieved stabilisation of the disease lasting maximally up to 248 days. Anaxirone is inactive in metastatic colorectal cancer.

Adult

[Treatment of anal cancer in Trøndelag].

We have retrospectively examined the medical records and prospectively studied the survival of 43 patients (37 women and six men) treated for anal cancer in the Trøndelag region of Norway during the period 1970-89. During this period, different strategies were used, ranging from primary surgery to combined chemo-radiotherapy and sphincter saving therapy. 20 patients were treated with surgery alone, nine patients first with surgery and postoperatively with irradiation because the surgery was non-radical (histologic), and 14 patients with combined chemo- and radiotherapy. The five year cancer ani-specific survival in the whole group is 69%. The predicted five year survival in the chemo-radiotherapy group is 90% versus 61% in the group treated with surgery. Primary chemotherapy combined with radiotherapy should be the preferred treatment for carcinoma of the anal canal.

Adult

Chemotherapy with or without high-dose medroxyprogesterone acetate in oestrogen-receptor-negative advanced breast cancer. Norwegian Breast Cancer Group.

In a randomised study 142 patients with advanced oestrogen-receptor-negative breast cancer in the tumour tissue received chemotherapy alone or chemotherapy combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 126 fully evaluable for response, the response rates were 46% for chemotherapy alone and 73% for chemotherapy with HD-MPA (P = 0.005). There was no significant difference with regard to duration of response. Of the 138 patients evaluable for survival and toxicity, survival was shorter in the combined treatment group; median survival of 9 versus 13 months (P less than 0.05). Considerable toxicity was seen from HD-MPA, especially weight gain and fluid retention. The present study provides evidence that in concordance with preclinical studies an interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. The side-effects from MPA were substantial, however, and the survival data are of great concern.

Antineoplastic Agents

Neuron-specific enolase--a serum tumour marker in seminoma?

The clinical significance of neuron-specific enolase (NSE) as a tumour marker was evaluated in 54 patients with seminoma. Before orchiectomy NSE was elevated in six out of 21 patients with stage I seminoma and 11 out of 16 patients with metastases. After orchiectomy NSE normalised in all evaluated stage I cases, but was still elevated in six out of 12 patients with metastatic disease. NSE monitored the effect of cisplatin-based chemotherapy in patients with metastases. In some patients, increased serum NSE was found together with raised levels of human choriogonadotropin (HCG) and lactate dehydrogenase (LDH), while in others only NSE was elevated. No false positive NSE values were observed. NSE seems to be a clinically worthwhile serum tumour marker for monitoring seminoma patients, with a sensitivity and specificity of the same order as HCG.

Biomarkers, Tumor

Oral magnetic particles in MR imaging of the abdomen and pelvis.

Two phase 2 clinical trials of an oral superparamagnetic contrast agent for enhancement on magnetic resonance images of the intestine were performed. In trial 1, 31 male patients with cancer of the testis underwent follow-up examinations of the abdomen at 0.5 and 1.5 T after oral administration of magnetic particles. In trial 2, 31 female patients with pelvic and lower abdominal disease were examined at 1.5 T after administration of the contrast material. The patients each ingested 800 mL of contrast material over approximately 2 hours. Concentrations of 0.25 and 0.5 g/L did not induce blurring or metallic artifacts. Distribution was homogeneous through the gastrointestinal tract. In all patients, a loss of signal intensity was observed on proton density-, T1-, and T2-weighted images. The diagnostic information from postcontrast images in trial 2 was greater in 16 patients (52%). Contrast enhancement was independent of field strength; no major side effects were observed. Artifacts from moving bowels were less troublesome, and delineation of intraabdominal and pelvic organs was better with the use of oral magnetic particles.

Abdominal Neoplasms

Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience.

Between 1981 and 1986, 200 consecutive patients with metastatic nonseminomatous testicular cancer were entered into the Swedish Norwegian Testicular Cancer (SWENOTECA) project from 14 hospitals. The treatment plan was four chemotherapy cycles (cisplatin, vinblastine, and bleomycin) followed by surgical resection of residual tumor masses. After a median observation time of 75 months, the overall 5-year survival rate was 82%. In a univariate analysis, the following parameters influenced the prognosis significantly: the extent of the disease (Medical Research Council [MRC] grouping); the prechemotherapy levels of serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH); the patients' age; the presence of extrapulmonary hematogeneous metastases; and/or particularly large lymph node metastases. Patients fared better when more than 3 weeks elapsed between orchiectomy and start of chemotherapy as compared with those who were treated within this interval. The place of treatment (a large oncology unit v smaller units) also represented a significant prognostic factor for patients with large-volume (LV) and very-large-volume (VLV) disease combined. Multivariate analysis (Cox regression proportional hazards model) performed in all 193 assessable patients showed the following adverse prognostic factors: high-volume metastatic burden, age older than 35 years, prechemotherapy AFP greater than 500 micrograms/L and/or HCG greater than 1,000 U/L, and an interval between orchiectomy and start of chemotherapy of less than 3 weeks. The place of treatment also significantly influenced the final outcome. If patients with LV and VLV disease were combined, the presence of two of the following risk factors represented an additional prognostic factor: AFP greater than 1,000 micrograms/L, HCG greater than 10,000 U/L, liver metastases, brain metastases, bone metastases, retroperitoneal tumor greater than or equal to 10 cm, and mediastinal tumor greater than or equal to 5 cm.

Adolescent

Early clinical stages of nonseminomatous testis cancer. Evaluation of the primary treatment and follow-up procedures of the SWENOTECA project.

During a 5-year period, 588 consecutive patients with nonseminomatous testicular germ cell cancer were included by 16 hospitals into the Swedish-Norwegian Testicular Cancer Project (SWENOTECA). A total of 370 (63%) had early clinical stages (CS1, CS1Mk+ and CS2A), and 345 (93%) of these patients underwent pathological staging (PS) by retroperitoneal lymph node dissection (RPLND). The overall clinical staging accuracy was 75%, with no significant difference between hospitals with low, medium or high patient accrual rate. Addition of bipedal lymphography did not improve the clinical staging accuracy compared to evaluation of the retroperitoneum by CT alone. Tumor serum markers before and close monitoring of the levels after orchiectomy gave valuable information regarding risk of retroperitoneal metastases. After a median follow-up period of 5 years 30 (13.8%) of 217 patients with PS1 disease relapsed, only 3 of them later than 18 months from the RPLND. Short orchiectomy to RPLND time interval, vascular invasion and absence of teratoma elements in the primary tumour were significant predictors of relapse in PS1 cases according to multivariate analysis. Unilateral RPLND was not associated with higher relapse rate than a bilateral procedure, but significantly reduced the risk of dry ejaculation after RPLND. None out of 122 PS2 patients who received adjuvant cisplatin-based chemotherapy after RPLND relapsed, despite the fact that 37 of them had only undergone a unilateral RPLND. Repeated CT examinations and most routine blood tests except serum alpha foeto protein (AFP), beta subunit of human chorionic gonadotropin (HCG) and lactate dehydrogenase (LD) may safely be omitted in the follow-up period for patients who have been pathologically staged with RPLND, provided that effective adjuvant chemotherapy has been given to the PS2 patients.

Antineoplastic Combined Chemotherapy Protocols

Serum tumour markers in testicular and extragonadal germ cell malignancies.

Serum tumour marker analyses are now an integral part of the modern management of patients with testicular or extragonadal germ cell tumours of the testis. AFP, HCG and may help in the diagnosis of extragonadal germ cell tumours in (young) males with malignancies of uncertain origin. AFP and HCG analyses play decisive roles in the classification, staging, choice of therapy and monitoring of treatment and follow-up of patients with nonseminomatous germ cell tumours. HCG, LDH and possibly NSE analyses are becoming important tools for the management of advanced seminoma, but there is a need for more reliable markers in this tumour type. Serum samples for AFP and HCG should be obtained before orchiectomy in any patient with a testicular tumour, as the pre-orchiectomy titres may represent important information for the subsequent clinical decision making. Cost-benefit estimates regarding the role of serum tumour markers in saving the life of patients with testis cancer are presented.

Biomarkers, Tumor

Proton nuclear magnetic resonance spectroscopy of plasma from healthy subjects and patients with cancer.

To evaluate the ability of proton nuclear magnetic resonance (NMR) spectroscopy to indicate the presence or absence of malignant disease, we analyzed plasma samples from 104 patients with untreated cancer of various types and from 164 healthy controls. All specimens were coded with random numbers, and the investigators were blind to patient category. A statistically significant difference (P less than 0.001) was found between the mean (+/- SD) line widths in the plasma samples from the controls (39.1 +/- 6.7 Hz) and the line widths in plasma from the patients with cancer (35.2 +/- 6.4 Hz). However, the values showed considerable overlap between the two groups. The average line widths in the 54 male (36.0 +/- 7.9 Hz) and the 110 female (40.5 +/- 5.6 Hz) controls were significantly different (P less than 0.001). Differences in the average line width were also found between 34 male controls 40 years old or older (33.9 +/- 6.5 Hz) and 20 younger men (39.6 +/- 8.8 Hz) (P = 0.008) and between 61 female controls 40 or older (38.8 +/- 5.7 Hz) and 49 younger women (42.5 +/- 4.7 Hz) (P less than 0.001). The average line widths in 36 women with cancer (35.5 +/- 6.8 Hz) and their controls matched for age and sex (39.0 +/- 6.3 Hz) were significantly different (P = 0.03) but again showed much overlap. In 29 men with cancer, the line widths were not different from those of controls matched for age and sex. We conclude that proton NMR spectroscopy is not generally reliable for the detection of cancer. Furthermore, our data demonstrate the importance of studying control groups matched for age and sex.

Adult

Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer.

One-hundred and seventy patients with estrogen receptor positive (greater than or equal to 10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg x 1 daily (TAM), or with TAM 30 mg x 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg x 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.

Antineoplastic Combined Chemotherapy Protocols

Weekly Adriamycin vs. 4-epidoxorubicin every second week in advanced breast cancer. A randomized trial. The Norwegian Breast Cancer Group.

One hundred and sixty-six patients with advanced breast cancer previously not treated with chemotherapy for metastatic disease were randomly allocated to 20 mg Adriamycin i.v. weekly (Awkly) as bolus injection or 50 mg 4-epidoxorubicin biweekly over a 3-h infusion time (EPIbiwkly). Of the 149 patients evaluable for response, the response rate was 36% for Awkly vs. 22% for EPIbiwkly (P = 0.10). There was no difference in response duration or survival. The main difference between the two regimens was in toxicity. Seventy per cent of Awkly patients virtually had no side-effects vs. 15% in the EPIbiwkly group. Significant differences in favour of Awkly were observed both for nausea/vomiting and alopecia.

Breast Neoplasms

Early clinical stages (CS1, CS1Mk+ and CS2A) of non-seminomatous testis cancer. Value of pre- and post-orchiectomy serum tumor marker information in prediction of retroperitoneal lymph node metastases. Swedish-Norwegian Testicular Cancer Project (SWENOTECA).

During a 5-year period (1981-86) 588 consecutive patients with nonseminatous germ cell tumors of the testis were included into a prospective Swedish-Norwegian multicenter study (SWENOTECA) and clinically staged according to the Royal Marsden system. A total of 370 patients (63%) had early clinical stages (CS) of disease; 295 (50%) had CS1, 32 (5%) had CS1Mk+ (CS1 with pathological serum tumor marker patterns after orchiectomy) and 43 (7%) had CS2A disease. Pathological staging with retroperitoneal lymph node dissection (RPLND) of the retroperitoneum was performed in 345 (93%) of the early CS patients and 128 (37%) had pathological stage 2 (PS2) disease; 27% of the CS1, 100% of the CS1Mk+ and 66% of the CS2A patients. The overall clinical staging accuracy was 75%. All the 40 patients with pathological serum AFP and/or HCG patterns before RPLND had PS2 disease, compared to 81/282 (29%) of patients with normal marker patterns. The PS2 patients with pathological marker patterns had significantly more and larger retroperitoneal metastases than those with normal AFP and HCG values. Elevated pre-orchiectomy AFP level indicated significantly reduced risk of PS2 disease in CS1 patients, but this effect became non-significant if the CS1Mk+ and CS2A cases were included into univariate or multivariate analyses. We suggest that the 'good risk' effect of pre-orchiectomy AFP elevation for CS1 cases may be caused by a selection mechanism during the clinical staging process.

Biomarkers, Tumor

Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group.

Between 1981 and 1986, 279 consecutive patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT) of the testis underwent pathological staging (PS) with retroperitoneal lymphadenectomy (RPLND). Patients with retroperitoneal metastases (PS2) received adjuvant chemotherapy. The median follow-up time after RPLND was 50 months (range, 30 to 90). Clinical and histopathologic features were registered prospectively and analyzed for association with risk of having PS2, relapse despite pathological stage 1 (PS1) or the combined risk of either event, metastatic disease (MET). Seventy-five (26.9%) of the patients had PS2 disease, and 30 (14.7%) of the 204 PS1 patients relapsed, indicating that at least 105 (37.6%) of this CS1 population had subclinical MET at the time of orchiectomy. Four (1.4%) of the 279 CS1 patients died of testicular cancer. Multivariate analyses showed several variables to be significantly associated with outcome for the CS1 patients; vascular invasion in primary tumor and normal preorchiectomy serum alpha-fetoprotein (Pre-AFP) level indicated PS2 disease. If Pre-AFP was excluded from the model, the absence of teratoma or yolk sac elements in the primary tumor became significant predictors of PS2. Vascular invasion, absence of teratoma, and a short interval between orchiectomy and RPLND indicated increased risk of relapse in PS1 patients. Vascular invasion, normal Pre-AFP, absence of teratoma elements, and a short orchiectomy to RPLND interval were predictive of MET. Our results indicate that prognostic factors useful for stratification of CS1 patients with NSGCT to different treatment options may be established.

Chorionic Gonadotropin

A randomized study on hormone-resistant prostatic cancer: estramustine phosphate versus low dose epirubicin with or without medroxyprogesterone acetate. A Norwegian multicenter study.

A prospective randomized study has been carried out in order to compare three different treatment modalities for symptomatic metastatic hormone-resistant prostatic cancer. A total of 79 patients were included. One group was treated with estramustine phosphate, another with Epirubicin plus Medroxyprogesterone acetate (MPA), while the third arm consisted of Epirubicin plus placebo. Best palliation was obtained by the combination of Epirubicin and MPA. This combination also seemed to be associated with the longest response duration.

Administration, Oral

Weekly anthracycline in the treatment of advanced breast cancer.

In two consecutive prospective and randomized studies, very similar response rates (31 and 36% respectively) were obtained for weekly 20 mg doses of doxorubicin among 143 patients with advanced breast cancer. The treatment was well tolerated and most patients had only moderate, if any, complaints about this treatment.

Breast Neoplasms