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G Daugaard

Publications and source records attributed to G Daugaard.

At least 55 records · Page 3Linked to original sources
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

Cisplatin nephrotoxicity: experimental and clinical studies.

Cisplatin is currently one of the most used agents in the treatment of cancer and it is essential in the treatment of germ cell cancer. The use of the drug is hampered by side effects - especially renal toxicity which is dose limiting. The present work was undertaken to elucidate the pathophysiological mechanisms involved in cisplatin induced nephrotoxicity. Immediately after administration of cisplatin to dogs, renal blood flow (RBF) and glomerular filtration rate (GFR) remained unchanged, while proximal reabsorption rates decreased significantly. The cisplatin induced nephrotoxicity is thus initiated by an acute, mainly proximal tubular impairment, preceding alterations in renal hemodynamics. These data were confirmed in a micropuncture study in rats. At 48 to 72 hours after administration of cisplatin depressed renal function could be attributed to impairment of proximal as well as distal tubular reabsorptive capacities, now associated with increased renal vascular resistance. After administration of 4 cycles of 20 mg cisplatin/m2 d. for 5 days in humans, a small but significant decrease in 51Cr-EDTA clearance was observed. In the high-dose cisplatin group (40 mg/m2 d. for 5 days) a severe progressive decrease in GFR was observed during treatment and GFR remained decreased for up to 2 years after termination of treatment. The observation of an acute increase in N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin indicates a primary tubular effect of cisplatin also in humans. A marked reduction of proximal tubular reabsorptive capacities of sodium and water was also observed in this group, together with a decrease in distal tubular function. These changes persist for at least 6 months after treatment. In the high-dose group proteinuria developed. This was mainly of tubular origin during cisplatin infusion and of glomerular origin between treatment cycles. Cisplatin remains one of the most potent antineoplastic agents ever developed. Further work should be performed to reduce its potential for renal toxicity.

Acute Kidney Injury↗
PubMed1989

Effects of antineoplastic treatment of HIV-positive patients with testicular cancer.

Among 101 patients with testicular cancer referred to the Department of Oncology ONB, Finsen Institute, four were proven HIV-positive before admission. Three of these patients were treated with cisplatin, 4-epi-podophyllotoxin (VP-16, Etoposide) and bleomycin. One patient with stage I of the testicular cancer was observed, after orchiectomy, without medical antineoplastic treatment. In the HIV-positive patients treated with cytotoxic drugs, leucopenia was seen after one (8%), fever after three (23%) and thrombocytopenia after two (15%) courses. Amongst patients not proven HIV-positive leucopenia, fever and thrombocytopenia were seen after 11 (9%), 21 (18%) and 27 (29%) courses. Two patients had stage II and two patients stage III of the HIV infection prior to treatment. The clinical stage of the disease did not change during the course of chemotherapy. We suggest that HIV-positive patients (stage II and III) with germ cell tumours should be treated with the same aggressive chemotherapy as given to other patients, not proven HIV-positive.

Adult↗
PubMed1988

Effects of cisplatin on different measures of glomerular function in the human kidney with special emphasis on high-dose.

To investigate the effect of high-dose cisplatin (40 mg/m2 daily for 5 days), 51Cr-EDTA clearance was used as a measure of glomerular filtration rate (GFR). 51Cr-EDTA clearance decreased significantly from 109 +/- 3 ml/min * 1.73 m2 to 68 +/- 3 ml/min * 1.73 m2 after three cycles of cisplatin and remained at this decreased level during the observation period (24 months). To determine the reliability of creatinine as a measure of GFR, we compared the simultaneous clearance of creatinine to that of 51Cr-EDTA. A good correlation between 51Cr-EDTA clearance and creatinine clearance was observed before and 3 months after termination of treatment, but no correlation was found during treatment. S-creatinine decreased significantly during treatment, probably due to muscle wasting. We conclude that s-creatinine and creatinine clearance are unsuitable measures of glomerular function during high-dose cisplatin treatment. All patients developed proteinuria during treatment. The changes in clearance ratios of beta-2-microglobulin/albumin and IgG/albumin show that the proteinuria observed during cisplatin infusion is predominantly of tubular origin, whereas the proteinuria between the treatment periods is mainly of glomerular origin.

Adult↗
PubMed1988

Renal tubular function in patients treated with high-dose cisplatin.

The effect of three cycles of high-dose cisplatin (40 mg/m2 day for 5 days) on renal tubular function was evaluated in 30 patients. A significant impairment of proximal tubular salt and water reabsorption rates was observed, but also distal tubular function seemed to be affected. These changes were also present 6 months after termination of treatment. Sodium and magnesium clearance increased significantly during treatment. Magnesium clearance normalized shortly after treatment but sodium clearance was significantly elevated 6 months after treatment. Proteinuria, albuminuria, and amino aciduria, together with an increase of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) excretion rates, were observed during each treatment cycle. A good correlation was registered between the increase in urinary excretion rates of protein, NAG, and magnesium and the decrease in proximal tubular salt and water reabsorption during cisplatin administration.

Acetylglucosaminidase↗
PubMed1988

Intrarenal blood flow distribution in dog kidney determined by 99mTc microaggregates and 201Tl.

Intrarenal distribution of blood flow was assessed with radioactive albumin microaggregates (MA) in three cortical zones of the dog kidney. The experimentally obtained zonal fractions of total renal blood flow were compared with predicted zonal blood flow fractions obtained in a mathematical model. The maximal degree of skimming that could possibly occur in a single experiment was estimated. The analysis showed that local blood flow in the inner cortical zone was maximally underestimated by 17% because of skimming of MA, and in the outer cortical zone the blood flow was maximally overestimated by 13% with the method of radioactive MA uptake. Renal uptake of 201Tl was measured simultaneously in exactly the same locations. Paired measurements of intrarenal blood flow distribution by MA and Tl uptake methodologies showed that local blood flow assessed with MA in the inner cortical zone was significantly lower than that obtained with 201Tl and that a higher blood flow rate was obtained in the outer cortical zone with MA compared with 201Tl. This disparity could be accounted for by the effect of skimming of MA as predicted by the model.

Animals↗
PubMed1988

Long-term effects on renal function and blood pressure of treatment with cisplatin, vinblastine, and bleomycin in patients with germ cell cancer.

Long-term effects of cisplatin on renal function were investigated in 34 patients with germ cell cancer observed for a median of 65 months (range, 43 to 97 months). All patients achieved a complete remission after treatment with cisplatin (median dose 583 mg/m2), vinblastine, and bleomycin. None of the patients relapsed during follow-up. During treatment the glomerular filtration rate (GFR) decreased by 18% (P less than .05). During follow-up kidney function recovered in ten patients and partly improved in eight patients. Changes in plasma creatinine did not consistently correspond to alterations in GFR. The mean increase in systolic blood pressure during follow-up did not differ from the increase seen in a group of age-matched healthy men. The mean increase in diastolic pressure, however, was significant (P less than .05), but was entirely due to hypertension observed in six patients. Renography of these patients was normal. We conclude that the decrease in GFR observed during treatment with cisplatin is partly reversible. Cisplatin-treated patients have an increased risk of developing hypertension years after treatment.

Adult↗
PubMed1988

Effect of cisplatin on proximal convoluted and straight segments of the rat kidney.

The immediate effect of cisplatin on rat proximal tubular function was investigated by two different methods, the lithium clearance method and the occlusion time-transit time method (TT-OT). Within minutes after administration of cisplatin a significant increase in lithium clearance, fractional lithium clearance (CLi/Cin) and e-TT/OT was observed (from 270 +/- 32 to 387 +/- 60 microliters/min/g kidney weight, 0.202 +/- 0.03 to 0.340 +/- 0.06 and 0.415 +/- 0.02 to 0.497 +/- 0.02, respectively). These increases indicate an increased fluid delivery from both the proximal straight segment and the late proximal convoluted tubule after cisplatin administration. Concomitantly absolute proximal reabsorption rate was significantly decreased. Intervention by saline loading (2% of body weight) did not prevent the increase in e-TT/OT, but the increase in CLi/Cin was significantly less than in the control group. This finding suggests that saline loading protects either the pars recta of the proximal tubule or the juxtamedullary nephrons. Thus, cisplatin-induced nephrotoxicity in the rat is initiated by an acute mainly proximal tubular impairment including both pars convoluta and pars recta of the proximal tubule.

Absorption↗
PubMed1987

Carcinoma-in-situ testis in patients with assumed extragonadal germ-cell tumours.

Testicular biopsies were done in 15 consecutive patients who were believed to have extragonadal germ-cell tumours. 8 patients (53%) had carcinoma-in-situ (CIS) in the gonads, although none had clinical signs of tumour. In addition, 3 of these patients had small areas of invasive tumour growth. Germ-cell tumours can only be diagnosed as being extragonadal in origin if testicular biopsy appearances are normal.

Adult↗
PubMed1987

Management of advanced metastatic germ cell tumours.

Forty patients with poor prognosis germ cell tumours were treated with a combination of cisplatin 40 mg/m2 and VP-16 200 mg/m2, both given days 1-5 every 3 weeks, and bleomycin 15 mg/m2 every week. Of thirty-three previously untreated patients twenty-eight (85%) patients obtained complete remission (CR) and four (12%) patients partial remission (PR). One patient was not evaluable for response. Twenty-four patients are alive 2-32 months after completion of therapy without evidence of disease (median observation 18.5 months). Of seven patients previously treated with cisplatin, five obtained CR (71%), one PR (14%) and one patient had progressive disease. Five patients are still alive, four without evidence of disease after a median follow-up of 22 months (range 16-25 months).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Effect of cisplatin on renal haemodynamics and tubular function in the dog kidney.

Administration of cisplatin (5 mg/kg) to dogs results in polyuric renal failure due initially to a proximal tubular functional impairment. 48-72 h after the cisplatin administration the depressed renal function can be attributed to impairment of proximal as well as distal tubular reabsorptive capacities associated with increased renal vascular resistance. The polyuria seems to be due to the impaired reabsorption rate in the distal nephron segments.

Animals↗
PubMed1987

Functional and histopathological changes in dog kidneys after administration of cisplatin.

The nephrotoxic effect of cisplatin (5 mg/kg i.v.) was evaluated in 8 dogs 48-72 h after administration. The lithium clearance method was used for assessing the absolute and fractional reabsorption rates of sodium and water in proximal as well as in more distal segments of the total nephron population, before and during saline loading (infusion of 5 ml/kg of isotonic saline i.v.). Histological examinations of the kidney biopsies were used to evaluate the degree of renal tissue injury. During 48-72 h after administration of cisplatin blood urea nitrogen and plasma creatinine increased significantly from 3.9 +/- 0.2 to 11.7 +/- 1.4 mmol/l and 96 +/- 3 to 178 +/- 10 mumol/l, respectively. Mean values of renal blood flow, glomerular filtration rate, filtration fraction and lithium clearance in cisplatin-treated animals (143 +/- 14 ml/min, 10.7 +/- 1.1. ml/min, 0.14 +/- 0.01 and 6.3 +/- 0.6 ml/min, respectively) were significantly lower than in 6 control animals (212 +/- 8 ml/min, 49.0 +/- 2.0 ml/min, 0.36 +/- 0.001 and 10.1 +/- 1.3 ml/min, respectively). In contrast, urinary excretion rates of sodium, potassium and water were significantly higher, while fractional as well as absolute proximal and distal reabsorption rates were significantly lower in cisplatin-treated animals compared to controls. Saline loading caused an increase in the output of tubular fluid from the proximal tubules (lithium clearance) in the cisplatin-treated animals, while the fractional distal reabsorption rate of sodium decreased significantly. The histological changes are in agreement with the physiological data which point to the proximal tubules as the more severely damaged segment. In conclusion, the depressed renal function 48-72 h after administration of cisplatin can be attributed to impairment of proximal as well as distal tubular reabsorptive capacities associated with increased renal vascular resistance. The polyuria seems to be due to impaired reabsorption rates in the distal nephron segments, which will affect the concentration mechanism.

Animals↗
PubMed1987

The renal handling of sodium and water is not affected by the standard-dose cisplatin treatment for testicular cancer.

Renal clearances of 51Cr-EDTA, lithium, sodium and potassium were measured before and after each of four consecutive treatment series with cisplatin in 15 men with testicular cancer. Since lithium is reabsorbed like sodium and water in the proximal tubules, but not reabsorbed to any measurable degree in the remainder of the nephron, lithium clearance equals the amount of fluid delivered from the end of the proximal straight segment to the thin descending limb of the loop of Henle. From the clearances of lithium and sodium, distal tubular reabsorption can be calculated. Lithium clearance and all other parameters of glomerular filtration and renal sodium handling remained normal throughout the study (with the exception of a fall in fractional sodium excretion after the first treatment series). Plasma magnesium declined during all four treatment periods, signifying renal magnesium wasting.

Adult↗
PubMed1986

Treatment of persistent or relapsing advanced germ cell neoplasms with cisplatin, etoposide and bleomycin.

Twenty-six patients, previously treated with cisplatin, vinblastine and bleomycin (pVB) had residual or recurrent germ cell tumors and were treated with cisplatin, etoposide and bleomycin (peB). Six patients obtained complete response and 11 patients partial response. Of the 11 patients with partial response 5 were disease free after post-chemotherapy surgery. Seven patients are still alive without evidence of disease with a median follow-up of 40 months (range 14+ - 57+ months). One patient died from acute non-lymphocytic leukemia without evidence of germ cell cancer. Toxicity was modest with only three patients having leukopenic fever. Retrospectively, the patients were analyzed in two groups according to their initial prognostic features. Thirteen patients were considered to have unfavourable prognostic factors and all had progress/relapse after treatment with peB. It is concluded that peB might be useful as first line therapy because of modest toxicity and considerable activity in pretreated patients and that more intensive therapy is necessary in patients with unfavourable prognostic features.

Adolescent↗
PubMed1986

High-dose cisplatin and VP-16 with bleomycin, in the management of advanced metastatic germ cell tumors.

Intensive combination chemotherapy consisting of cisplatin 40 mg/m2 daily X 5, VP-16 200 mg/m2 daily X 5 and bleomycin 15 mg/m2 every week was administered to 29 patients (22 previously untreated and seven previously treated) with poor prognosis germ cell tumors. Eighty-six per cent of the previously untreated patients obtained CR and 5% PR. Seventeen patients (77%) are alive without evidence of disease after a median observation time of 11 months (range 1+-19+ months) after treatment. Seventy-one per cent of the previously treated patients obtained CR and 14% PR. Six patients are still alive and four (57%) without evidence of disease after a median observation time of 9 months (range 3+-12+ months) after treatment. Toxicity was severe in both groups. In 73% of the cycles WBC was below 1.0 X 10(9)/1, and in 74% of the cycles thrombocytes was below 25 X 10(9)/1. Ninety-one per cent had at least one incidence with culture negative neutropenic fever, and in four patients bacteremia was documented. Kidney function decreased (median 33%) in previously untreated patients as measured by 51Cr-EDTA clearance. Ototoxicity was observed in around 60% of the patients (two patients has required the use of a hearing aid) and neurotoxicity in around 40%. Neurotoxicity was mild in most cases. The results of the present investigation are encouraging and justify an aggressive therapeutic approach to patients with poor prognosis germ cell tumors. The toxicity is substantial, but manageable, and only a prospective randomized study can substantiate whether this excess in toxicity can be translated into an improved survival and cure.

Adolescent↗
PubMed1986

Acute effect of cisplatin on renal hemodynamics and tubular function in dog kidneys.

The present study was designed to investigate the early hemodynamic and tubular effects of cisplatin administration on dogs. To localize the nephrotoxic actions of cisplatin, we have taken advantage of the lithium clearance method. After infusion of 5 mg of cisplatin per kg, an immediate and significant increase in urinary flow rate (from 0.39 +/- 0.07 ml/min to 0.73 +/- 0.12 ml/min), sodium clearance (from 0.33 +/- 0.11 ml/min to 0.65 +/- 0.14 ml/min), potassium clearance (from 9.23 +/- 0.48 ml/min to 10.77 +/- 0.95 ml/min), lithium clearance (from 15.55 +/- 2.21 ml/min to 23.76 +/- 4.00 ml/min) and fractional lithium clearance (from 0.31 +/- 0.03 to 0.44 +/- 0.04) was seen. This occurred without measurable changes in glomerular filtration rate and renal blood flow. The calculated fractional as well as absolute rates of proximal reabsorption of sodium decreased significantly from 0.68 +/- 0.03 to 0.56 +/- 0.04 and from 4.76 +/- 0.32 mmol/min to 3.92 +/- 0.23 mmol/min, respectively. The results show that administration of cisplatin causes an acute, mainly proximal tubular impairment in dogs without alterations in renal hemodynamics.

Animals↗