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R von Roemeling

Publications and source records attributed to R von Roemeling.

18 recordsLinked to original sources
PubMed1990

Determination of the therapeutic index of floxuridine by its circadian infusion pattern.

To test if circadian timing of a drug is important for its toxicity and antitumor activity, we compared the circadian patterns observed with seven equal doses of floxuridine (FUDR) infused either at a variable rate or at a constant rate in female F344 rats. For the variable-rate infusion, the daily dose of FUDR was divided into four 6-hour portions of 68%, 15%, 2%, and 15% to achieve a quasisinusoidal pattern. Peak drug delivery occurred during one of six different times of day. At a dose level resulting in 50% overall mortality, lethal toxicity differed significantly, depending on the circadian stage of maximum drug delivery. Depending on the circadian stage of maximum drug flow, variable-rate infusions were more toxic than or as toxic as constant-rate infusion. FUDR lethality was lowest when constant-rate infusion was used or when variable-rate infusion peaked during the late activity-early rest span of the recipients. The circadian pattern of variable-rate infusion also determined the antitumor activity in tumor-bearing rats. At a therapeutic dose level and at identical dose intensity, the variable-rate-infusion pattern, with peak drug flow during the late activity-early rest span, resulted in significantly greater delay in tumor growth than was observed with either the constant-rate infusion or other variable-rate patterns. We conclude that the toxicity and antitumor activity of FUDR depend on the circadian timing of the infusion peak when the drug is given by variable-rate infusion. Since some of the circadian-shaped infusions studied are toxicologically and therapeutically inferior to constant-rate infusion, the circadian pattern and not the quasi-intermittency of circadian FUDR administration is primarily responsible for these pharmacodynamic differences.

Adenocarcinoma↗
PubMed1990

Circadian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma.

Sixty-eight unselected patients with progressive metastatic renal cell carcinoma (RCC) were treated between March 1985 and November 1988 with continuous infusion floxuridine (FUDR). Thirty-seven percent of these patients had previously received and failed systemic treatment. Using implantable pumps for automatic drug delivery, FUDR was continuously infused for 14 days at monthly intervals. The starting dose was 0.15 mg/kg/d (intravenous [IV]; n = 61) or 0.25 mg/kg/d (intraarterial [IA]; n = 7); IV doses were increased or decreased in increments of 0.025 mg/kg/d as permitted by toxicity. Diarrhea (with or without mild abdominal cramping) and nausea/vomiting limited the FUDR IV infusion, and hepatic function abnormalities limited FUDR IA infusion. The use of a circadian-modified infusion schedule permitted high FUDR doses to be safely given as compared with a constant rate infusion schedule. Of 63 patients assessable for response, 56 received systemic FUDR infusion. Four complete responses (CRs; 7.1%); and seven partial responses (PRs; 12.5%) were observed (objective response rate, CR plus PR, 19.6 +/- 5.1% [95% confidence limits] ). The median objective response duration was 10.8 months (range, 1 to 18 months; mean, 9.4 +/- 1.6). Four additional patients had minor tumor responses (MRs; 7.1%). In a subgroup of seven assessable patients receiving hepatic arterial FUDR, we observed one CR and three PRs (57.2 +/- 42.8%). Overall, objective response (CR plus PR) was seen in a quarter of assessable patients treated, 15 of 63, while only 15 of the 63 assessable patients (25.4%) have had objective tumor progression. The median follow-up time for all 68 patients was 28 months (range, 1 to 42), and their median survival duration is 15 months (range, 3 to 37 months). Continuous infusion FUDR is an effective outpatient treatment for progressive metastatic RCC, producing durable tumor response and causing little toxicity.

Adult↗
PubMed1990

Improved therapeutic index of cisplatin analogue: B-85-0040 by circadian timing.

1. B-85-0040 is a new cisplatin analogue with dose limiting myelosuppression. 2. The maximum tolerated dose ranges between 300 and 525 mg/kg for single i.p. bolus injection in mice. 3. Its toxicity is circadian-stage dependent with optimal tolerance between 16 and 17 hours after lights on. 4. B-85-0040 is active in L1210 leukemia. Anti-tumor activity seems to be unrelated to the circadian stage of treatment. Optimal drug timing can therefore increase its therapeutic index.

Animals↗
PubMed1989

Circadian patterning of continuous floxuridine infusion reduces toxicity and allows higher dose intensity in patients with widespread cancer.

Continuous long-term 5-fluoro-2'-deoxyuridine (floxuridine; FUDR) infusion frequently causes severe and dose-limiting gastrointestinal toxicity when administered at a constant rate at commonly prescribed dose levels. In preclinical studies, a circadian infusion pattern peaking late in the daily activity phase was better tolerated and had superior antitumor activity than a constant infusion against a transplanted tumor. Based upon these data and upon other chronobiological cytokinetic and pharmacologic considerations, we compared a circadian patterned variable rate infusion with a maximal flow rate in the late afternoon/early evening and minimum flow rate during the early morning hours to a constant rate infusion in 54 patients with widespread cancer. All FUDR infusions were administered using an implanted drug pump. In a pilot crossover study and a second randomized trial, patients with metastatic malignancies treated with equal dose intensities experienced less frequent and less severe diarrhea, nausea, and vomiting following variable rate infusion. In a third study, the dose intensity of variable rate infusion was escalated stepwise to determine the maximum-tolerated dose. Patients receiving time-modified FUDR infusion tolerated an average of 1.45-fold more drug per unit time while evincing minimal toxicity. FUDR infusion was found to have activity against progressive metastatic renal cell cancer (RCC). Increased dose intensity achieved by optimal circadian shaping may improve the therapeutic index of infusional FUDR and may help control malignancies that are refractory to conventional chemotherapy.

Carcinoma, Renal Cell↗
PubMed1988

Circadian rhythm and seasonal dependence in the toxicological response of mice to epirubicin.

Compared to doxorubicin, equimolar epirubicin toxicity is reduced by about 50% by the epimerization of a hydrogen and hydroxyl group at the 4' position of the anthracycline sugar moiety. The circadian timing of doxorubicin administration markedly affects its lethal and sub-lethal bone marrow and gut toxicities in mice, as well as the severity of its clinical toxicity. We tested whether the timing of administration of equitoxic epirubicin doses similarly affected the toxicological response in female CD2F1 mice. A large and highly reproducible effect of the circadian stage of administration was documented with best drug tolerance occurring during the first half of the daily rest (light) span of the animals. In addition to this circadian rhythm, a significant seasonal effect was found with significantly fewer deaths occurring after epirubicin was given in the Summer, as compared to the Winter. Safest circadian timing for epirubicin is statistically significantly earlier in the day than for doxorubicin, while their seasonal patterns are quite similar.

Animals↗
PubMed1988

Methylene blue protects intestinal mucosa from free radical-mediated sublethal radiation damage.

Susceptibility of the intestine to radiation damage is a primary reason for the failure of external beam radiation to cure intra-abdominal cancer. High-dose irradiation causes intestinal denudation, fluid loss, and resultant shock. Simple and effective methods for protecting the intestine from irradiation damage are not available. Many biological effects of ionizing irradiation are caused by free radical intermediates. We have previously reported that many of the toxicities of doxorubicin, a classic free radical generating anticancer agent, are blocked by methylene blue pretreatment. We have now found that pretreatment with methylene blue protects rats from intestinal damage, as measured histologically and by quantitative stool blood determinations. Whereas the exact mechanisms of this protection remain elusive, we believe this method of modulating the therapeutic index of ionizing radiation deserves additional preclinical and clinical study.

Animals↗
PubMed1988

Progressive metastatic renal cell carcinoma controlled by continuous 5-fluoro-2-deoxyuridine infusion.

We treated 19 patients with progressive metastatic renal cell carcinoma with continuous infusion of 5-fluoro-2-deoxyuridine, 52 per cent of whom had previously received and failed chemotherapy. Implantable pumps were used for automatic drug delivery. 5-Fluoro-2-deoxyuridine was infused continuously for 14 days at monthly intervals. The starting dose was 0.15 mg. per kg. per day (intravenous) or 0.25 mg. per kg. per day (intra-arterial). Intravenous doses were increased or decreased in increments of 0.025 mg. per kg. per day as permitted by toxicity. Abdominal pain, diarrhea and mucositis limited the intravenous infusion, while malaise, anorexia and hepatic function abnormalities limited intra-arterial infusion. Of 18 evaluable patients we observed 1 complete, 4 partial (objective response rate 28 per cent) and 2 minor responses. The duration of response ranged from 2 to greater than 18 months. During a median follow up of 7.5 months (range 2 to 21 months) only 4 of the 18 patients had objective tumor progression. Over-all survival for the 19 patients was 94 per cent. Continuous infusion of 5-fluoro-2-deoxyuridine may be effective for the treatment of progressive renal cell carcinoma.

Adult↗
PubMed1979

[Clinical expressions of plasmocytoma (author's transl)].

Multiple myeloma is the most frequent type of hemoblastic disorders including paraproteinemia. Most cases show a disseminated involvement; few patients have solitary lesions of the bones or connective tissues. Different localizations are the reason for the multiform clinical picture of the disease. The main symptoms result from neurological and dermatological involvement, less usual are gastrointestinal complaints. Fractures, neurological deficiencies, lack of antibodies and failure of the kidneys determine the course of plasmocytoma. Our case reports are demonstrating examples of the different clinical expressions.

Aged↗
PubMed1978

[Treatment results of therapy resistant acute leukemias with 7 cystostatic agents (TRAMPCO-scheme)].

Treatment of therapy-resistant acute leukemia with 7 cytostatics (TRAMPCO) 13 adult patients with acute leukemia, primarily and secondarily resistant to other combined therapy, as well as 2 untreated patients were treated with 7 cytostatic drugs according to the so called TRAMPCO-regimen. 5 complete remissions and 5 partial remissions were obtained corresponding to a degree of response of 66%. The duration of remission was relatively short with 1 to 5 months, in one case more than 6 months. The toxicity of the combined therapy could be tolerated, the personal subjective tolerance was good. The Trampco-regiment therefore represents a realistic possibility in the treatment of acute leukemia resistant to other forms of treatment.

Acute Disease↗
PubMed1978

[What are the dangers of splenectomy in Hodgkin's disease?].

Splenectomy is a surgical procedure of medium severity, the mean lethality rate is 1%, the complication rate 10 to 20%. The surgical risk is dependent upon age and general condition of the patient, the severity of the disease, and the experience of the surgeon. The risk of late complications due to surgery is determined mainly by infections as well as ileus, requiring relaparatomy. The risk of infections is higher in children than in adults: one has to be aware of miningitis and sepsis in about 10% of the patients; half of those cases end lethal. An analysis of advantages versus risks of splenectomy must be made for each patient individually. For optimal treatment it is necessary to know the stage of the disease. Concerning M. Hodgkin, explorative laparatomy combined with splenectomy should be performed in stage I to III A. If, however, the surgical risk is rather high primarily and if there are no therapeutical consequences to be expected, splenectomy should not be performed because of the known risks and disadvantages.

Adult↗
PubMedDate not supplied

MR imaging of patients with implanted drug infusion pumps.

The influence of magnetic resonance (MR) imaging on the integrity and function of an implantable, programmable drug infusion pump and the distortion of the image by this device were tested. Six identical pumps were tested in magnetic fields of 1.5 T. Pump memory was not affected by the procedure. The pump rotor stalled (no infusion) as long as the device was within the magnetic field. Drug delivery resumed as programmed after the pump was removed from the field. No structural damage to the electrical or mechanical pump components was detected. The pump caused a circular image artifact (a signal dropout) within 8-10 cm of the device. The authors conclude that MR imaging is accurate if the area of interest is at least 10 cm from the pump, and that with awareness of temporary infusion cessation, it is safe to perform MR imaging in patients with this implanted pump.

Artifacts↗
PubMedDate not supplied

Circadian-based infusional FUDR therapy.

FUDR (5-fluoro-2'-deoxyuridine) is one of the few chemotherapeutic agents with activity against metastatic renal cell cancer. Diarrhea and dehydration with long-term, constant-rate intravenous infusion may be severe and life-threatening. This gastrointestinal toxicity can be reduced by altering the rate of the infusion so that most of the daily dose is given late in the day, and a minimal infusion rate is delivered in the early morning hours. This complex therapy can be automatically administered by the programmable, implantable Synchro-Med Infusion System. Using a circadian modification of infusion delivery, toxicity is diminished and the FUDR dose can be safely increased, which may result in greater anti-tumor activity. This paper describes Phase I studies with 54 patients who were treated with intravenous FUDR. It also discusses results of a Phase II study using circadian-modified intravenous delivery of FUDR in the treatment of 61 patients with renal cell cancer. It outlines the nursing implications for management of the implantable, programmable drug delivery system and addresses the nursing role in preventing, recognizing, and controlling FUDR-associated toxicities.

Carcinoma, Renal Cell↗