Melphalan in the Treatment of Myelomatosis

Speed, Dorothy E.; Galton, D. J.; Swan, Alexander M

doi:10.1136/bmj.1.5399.1664

Cited by 34 publications

(11 citation statements)

References 7 publications

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“…Although the alkylating agent melphalan is commonly used in myeloma patients with renal failure, it is not known whether renal dysfunction alters its pharmacokinetics or marrow toxicity. Speed et al (1964) suggested that the rate of melphalan urinary excretion might be decreased in the presence of renal failure. We have studied the disposition and marrow toxicity of melphalan in dogs before and after surgically induced renal failure.…”

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confidence: 99%

“…melphalan-induced myelosuppression is markedly increased and its plasma elimination and renal clearance significantly decreased in the presence of renal dysfunction in dogs. These data suggest that parenteral melphalan's starting dose be decreased by at least 50%o when used in myeloma patients with renal failure.MELPHALAN continues to be one of the most important anticancer drugs in the treatment of multiple myeloma (Speed et al, 1964;Alexanian et al, 1968;Bergsagel et al, 1979). As many as one third of all myeloma patients will have severely reduced renal function as a result of renal tubular damage from paraprotein deposition and/or the toxic effects of hypercalcaemia (Kayle & Bayrd, 1976).…”

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“…MELPHALAN continues to be one of the most important anticancer drugs in the treatment of multiple myeloma (Speed et al, 1964;Alexanian et al, 1968;Bergsagel et al, 1979). As many as one third of all myeloma patients will have severely reduced renal function as a result of renal tubular damage from paraprotein deposition and/or the toxic effects of hypercalcaemia (Kayle & Bayrd, 1976).…”

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Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan

Alberts¹,

Chen²,

Benz³

et al. 1981

Br J Cancer

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Summary.-The effect of renal failure on melphalan pharmacology and toxicity has been poorly understood. Such information is of interest because melphalan is the most commonly used anticancer drug in the treatment of multiple myeloma, which is frequently associated with renal failure. We have studied the disposition and marrow toxicity of parenteral melphalan in dogs before and after induction of renal failure with subtotal nephrectomy. The surgical procedure decreased the creatinine clearance by an average of 62% (P=0-001). The lowest neutrophil counts following i.v. melphalan (1 mg/kg) averaged 4.9 x 103/mm3 pre-nephrectomy and 0-9 x 103/mm3 post -nephrectomy, respectively (P = 0.002). The mean lowest recorded platelet counts after melphalan (1 mg/kg) were 115 x 103/mm3 in the pre-nephrectomized dogs, and 9-7 x 103/mm3 in those who had been nephrectomized (P=0.002). Following nephrectomy, i.v. melphalan's terminal-phase plasma half-life and renal clearance were both raised (P=0.02) to 75%O over pre-nephrectomy values. These studies show that i.v. melphalan-induced myelosuppression is markedly increased and its plasma elimination and renal clearance significantly decreased in the presence of renal dysfunction in dogs. These data suggest that parenteral melphalan's starting dose be decreased by at least 50%o when used in myeloma patients with renal failure.MELPHALAN continues to be one of the most important anticancer drugs in the treatment of multiple myeloma (Speed et al., 1964;Alexanian et al., 1968;Bergsagel et al., 1979). As many as one third of all myeloma patients will have severely reduced renal function as a result of renal tubular damage from paraprotein deposition and/or the toxic effects of hypercalcaemia (Kayle & Bayrd, 1976). Although the alkylating agent melphalan is commonly used in myeloma patients with renal failure, it is not known whether renal dysfunction alters its pharmacokinetics or marrow toxicity. Speed et al. (1964) suggested that the rate of melphalan urinary excretion might be decreased in the presence of renal failure. We have studied the disposition and marrow toxicity of melphalan in dogs before and after surgically induced renal failure. The results of these studies suggest that severe renal dysfunction can slow the plasma and renal clearance of melphalan and markedly increase neutropenia and thrombocytopenia. MATERIALS ANI) METHODSDogs.-Eight male mongrel dogs, weighing 17-23 kg, which had been previously quarantined for 2-4 weeks in the vivarium, were used. The dogs were without evidence of infection and were not given other drugs during the entire duration of the melphalan studies. Baseline BUN, serum creatinine, and 24h urinary creatinine clearance were measured in each of the animals, and were remeasured after the surgical induction of renal dysfunction.An indwelling 16-gauge catheter was inserted into a superficial leg vein. Melphalan(1 mg/kg body weight) wAas injected i.v. over about 1 min, followed by 10 ml normal

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Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan

Alberts¹,

Chen²,

Benz³

et al. 1981

Br J Cancer

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“…In this trial the median survival of 25 months from the start of treatment, in the 221 patients whose blood urea concentration at presentation was below 80 mg/100 ml, is not greatly different from other figures in published reports. From two preliminary trials of melphalan therapy (Speed et al, 1964;Waldenstrom, 1964) it seemed possible that intermittent administration at high dosage was less likely to damage the bone marrow than continuous administration, but might also be less effective in controlling the disease. During the course of this trial the method of intermittent administration was reported to be more effective, and the addition of prednisone during each course of melphalan was found to give even better results (Bergsagel et al, 1967;Alexanian et al, 1969).…”

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confidence: 99%

Myelomatosis: Comparison of Melphalan and Cyclophosphamide Therapy

1971

BMJ

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“…Different authors have taken different criteria as indices of successful treatment. Waldenstrom (1964) for instance regards the return of serum protein anomalies to normal as an important criterion; Speed, Galton & Swan (1964), the overall symptomatic improvement, and the Acute Leukaemia Cooperative Group, an improvement in survival times.…”

Section: Introductionmentioning

confidence: 99%

The management of myelomatosis

Broad

Godlee

Emery

et al. 1968

Postgraduate Medical Journal

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SummaryThirty-six out of sixty-two cases of myelomatosis have been treated with melphalan.Platelet counts were used as a guide to dosage early in the course of treatment, after which a more empirical dosage (0-15 mg/kg/ day) was used in 1-week courses given every 12 weeks. Rapid deterioration and death occur in a small number of patients whatever therapy is given.In the group treated with melphalan the median survival time was 25 months, longer than in those treated with radiotherapy or other chemotherapeutic agents.

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Melphalan in the Treatment of Myelomatosis

Cited by 34 publications

References 7 publications

Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan

Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan

Myelomatosis: Comparison of Melphalan and Cyclophosphamide Therapy

The management of myelomatosis

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