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Biomedical subjects

O Klepp

Publications and source records attributed to O Klepp.

At least 37 records · Page 2Linked to original sources

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↗

PharmCalc: program for the calculation of clinical pharmacokinetic parameters of methotrexate.

A new program package (PharmCalc) has been developed for the calculation of basic pharmacokinetic parameters (half-time, systemic clearance, renal clearance, AUC, volume of distribution, CSF/serum distribution ratio) of methotrexate (MTX). The program helps in the early recognition of patients at risk for toxicity and calculates the dosage of folinic acid rescue adjusted to the serum levels of MTX. The program offers a standardized and automated evaluation procedure for MTX pharmacokinetics and provides an easy-to-use tool for further research in this field. The concept and routines of the program are described.

Drug Therapy, Computer-Assisted↗

Lack of gonadal protection by medroxyprogesterone acetate-induced transient medical castration during chemotherapy for testicular cancer.

The serum FSH levels were analysed in 24 testicular cancer patients 3 to 9 years after intensive chemotherapy. Sperm cell counts were performed in 12 patients. In all cases a temporary medical castration had been achieved during intensive chemotherapy by the use of medroxyprogesterone acetate (MPA) (500 mg daily per os). The hormone treatment was initiated on day 1 of the first chemotherapy cycle. Thirteen additional patients did not receive this hormone treatment but were treated by similar chemotherapy. The latter patients served as a control group. There was a tendency towards higher FSH levels in the MPA-treated patients than in the controls. Following treatment, serum testosterone was significantly lower in patients who had received MPA during their intensive chemotherapy than in the controls. There was no difference between the groups with regard to recovery of sperm cell production after chemotherapy. An MPA-induced medical castration during intensive chemotherapy in testicular cancer patients is ineffective in protecting the remaining testis against treatment-induced damage to spermatogenesis, at least if hormone treatment is started simultaneously with chemotherapy.

Adult↗

Long-term survival and morbidity in patients with metastatic malignant germ cell tumors treated with cisplatin-based combination chemotherapy.

Forty-three of 79 patients treated for clinically metastatic germ cell cancer survived for a median of 66 months (range, 52-83). In patients without previous chemotherapy the 5-year survival rate was 69%, whereas only 32% of patients with prior chemotherapy survived for 5 years. Limited disease, complete clinical response, histopathologically proven postchemotherapy tumor necrosis or complete resectability of a posttreatment mature teratoma indicated a favorable prognosis in patients without prior chemotherapy. Only 20% to 30% of the patients with less than a clinical complete response or with posttreatment residual malignant tumor can be salvaged by second line therapy. Posttreatment mature teratoma should be resected completely whenever possible, as this condition may lead to reactivation of the malignancy even after several years. Raynaud-like phenomena and/or gastrointestinal problems are the main long-term sequel (10%-15%) after modern multimodality treatment of advanced germ cell cancer (fertility-related problems are not considered here). In the majority of surviving patients, the lifestyle seems unaffected by the previous intensive treatment, evaluated about 5 years after discontinuation of all therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Weekly adriamycin versus VAC in advanced breast cancer. A randomized trial.

In a prospective randomised study 128 patients with advanced breast cancer were treated either with Adriamycin (20 mg/week) or vincristine, Adriamycin and cyclophosphamide (VAC). An objective response was obtained in 31 and 35% of patients in the two groups. There was no significant difference with regard to duration of response or survival. Weekly low dose Adriamycin was well tolerated. When subjective side effects occurred, they were usually slight and transient. In approx. 40% of the patients no side-effects at all were observed. Eight per cent had alopecia requiring a wig. Only slight myelosuppression could be seen in a few patients and this had no practical implications. Most or all of VAC patients experienced severe toxicity with regard to nausea, vomiting and alopecia. Also myelosuppression was more pronounced among VAC patients. It is concluded that weekly doses of Adriamycin as single agent therapy for advanced breast cancer is as effective as the VAC combination delivered every third week, with considerably less toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Transient vinblastine-induced thrombocytopenia during chemotherapy with vinblastine, cis-platinum and bleomycin.

An early, transient drop in peripheral blood platelets to a mean nadir value of 49% (range 31-83%) of the pretreatment value was seen in 31 patients during chemotherapy with cis-platinum, vinblastine and bleomycin (PVB). The mean number of platelets dropped by 22% during the first 24 h after the start of chemotherapy, nadir value was seen after 3 d, with recovery to 107% of pretreatment level on d 14-15. Platelet survival studies during PVB chemotherapy showed shortened platelet survival time and indicated increased destruction of platelets. Identical patterns of early, transient thrombocytopenia were seen in 6 patients treated with vinblastine only. The early fall in circulating platelets did not predict subsequent serious thrombocytopenia. There were no bleeding episodes in the 37 patients studied here, but the early thrombocytopenia seen after vinblastine therapy may possibly be of clinical importance in critically ill patients at risk for bleeding episodes. In rats, an early drop in circulating platelets occurred after a high dose of vinblastine, but not after bleomycin. Addition of bleomycin to vinblastine did not increase the vinblastine-induced thrombocytopenia. It is concluded that the early drop in peripheral blood platelets during chemotherapy with PVB is due to vinblastine.

Animals↗