Estramustine affects bone mineral metabolism in metastatic prostate cancer

Abstract

A patient with metastatic prostate cancer is described where treatment with Adriamycin (doxorubicin) and estramustine produced severe hypophosphatemia (serum phosphate level, 1.2 mg/dl), which was reversible when treatment was discontinued. Previous studies have shown no effect of Adriamycin on serum phosphate levels. A retrospective study of serial serimm chemistry values was done in 15 patients treated with estramustine. A significant fall in the serum phosphate level (mean, 0.8 f 0.3 mg/dl) was observed during the first 6 weeks of treatment. When compaired with similar patients treated with bilateral orchiectomy, estramustine-treated patients had lower levels of serum calcium, fractional excretion of calcium, serum phosphate, and renal tubular threshold for phosphate reabsorption (TmPO,/GFR). Qualitatively similar but quantitatively smaller effects were also seen in a group of patients treated with diethylstilbestrol (DES) in a dose of 1 to 3 mg daily. Estrainustine appears to have significant effects on bone mineral metabolism, particularly on renal phosphate handling resulting in significant hypophospha-temia. This is probably due to an estrogenic effect. Cancer 58:2208-2213, 1986. STRAMUSTINE PHOSPHATE IS AN ORAL AGENT used E in the treatment of prostate cancer.'-6 It is a conjugate of estradiol 17p and an alkylating agent (mechlor-methamine). The precise mode of action of the drug is not Estramustine has been reported to produce responses in 10% to 35% of patients with metastatic pros-tate cancer no longer responsive to conventional hormone treatment." Toxicity is similar both qualitatively and quantitatively to that of diethylstilbestrol (DES) and includes nausea and vomiting, gynecomastia, fluid retention, thrombo-phlebitis, and occasional elevation of liver function tests. It is believed that estramustine owes part of its therapeutic action and toxicity to a high-dose estrogen effect.' For the past several years, we have treated patients with advanced (Stage D) prostate cancer whose disease is resistant to conventional hormone treatment with estra-mustine, either alone or in combination with Adriamycin (doxorubicin). In one patient, severe hypophosphatemia developed that was reversed only with discontinuation of

Weekly paclitaxel plus estramustine combination therapy in hormone‐refractory prostate cancer: A pilot study

“…Dose‐limiting toxicity such as protracted nausea was related to EMP in this study. The asymptomatic hypophosphatemia and hypocalcemia observed in our patients may also be attributed to an estrogenic effect of EMP 24,25 . EMP is known to have a significant effect on bone mineral metabolism, particularly on renal phosphate handling, which can result in significant hypophosphatemia 26 .…”

“…EMP is known to have a significant effect on bone mineral metabolism, particularly on renal phosphate handling, which can result in significant hypophosphatemia 26 . Hypocalcemia has frequently been seen in association with institution of estrogen therapy 24,25 . Thus, the role and contribution of EMP needs to be explored further in adequately designed studies on Asian males.…”

Recurrent persistent hypophosphatemia in a male‐to‐female transgender patient with anorexia nervosa: Case report

“…However germane to this case, although spironolactone does not cause hypophosphatemia, it is suspected that high‐dose estrogen may adversely impact serum phosphorus levels by increasing urinary losses. The administration of large doses of estrogens in male patients with metastatic prostatic cancer, and also mestranol in oophorectomized women, have indeed been reported to cause hypophosphatemia due to a decrease in renal phosphate reabsorption (Aitken, Hart, & Smith, ; Citrin, Elson, Kies, & Lind, ; Citrin et al, ; Liamis et al, ; Uemura, Irahara, & Yoneda, ). Moreover, data suggest that renal phosphate wasting and hypophosphatemia induced by estrogen are secondary to down‐regulation of NaPi‐IIa in the proximal tubule causing renal wasting (Faroqui, Levi, Soleimani, & Amlal, ).…”

Hypophosphatemia in cancer patients

“…The level returns to normal upon discontinuation of treatment. The phosphaturia etiology is attributed to the estrogen effect on proximal tubules with downregulation of NaPi-2a [ 83 , 84 ].…”