Management of hypocalcemic effects of WR2721 administered on a daily times five schedule with cisplatin and radiation therapy. The New York Gynecologic Oncology Group.
OBJECTIVE
To determine the effects of the chemoprotective agent, WR2721, administered on a daily x 5 schedule with cisplatin and radiation therapy, on calcium and parathyroid hormone (PTH) levels.


METHODS
Twenty women with cervical cancer were enrolled in a clinical trial to determine the maximal safe dose of WR2721 plus radiation therapy and cisplatin on a novel daily x 5 schedule. Detailed studies of the effects of WR2721 on calcium and PTH levels were initiated after a patient developed symptomatic hypocalcemia.


RESULTS
Treatment with WR2721 resulted in a rapid decline in serum PTH levels within 4 hours, which fell below the lower limits of normal at 24 hours, then returned to within normal limits at 48 hours. In contrast, serum levels of ionized calcium were not affected acutely, and declined by only 7% within 24 hours. However, this small decrease persisted for the 5 days of treatment. Hypocalcemic effects were successfully managed with oral calcium carbonate and calcitriol supplements. In one patient, particularly sensitive to the effects of WR2721, serum levels of ionized calcium decreased to less than 3.0 mg/dL despite oral calcium supplements.


CONCLUSIONS
The effects of WR2721 on serum ionized calcium levels are mediated by direct inhibition of PTH activity; other effects such as inhibition of renal tubular calcium reabsorption cannot be excluded. We recommend that patients treated with WR2721, cisplatin, and radiation therapy receive routine oral calcium and calcitriol supplementation and that serum ionized calcium levels be monitored frequently.
Wadler
S
S
Albert Einstein Cancer Center, Bronx, NY.
Haynes
H
H
Beitler
J J
JJ
Goldberg
G
G
Holland
J F
JF
Hochster
H
H
Bruckner
H
H
Mandeli
J
J
Smith
H
H
Runowicz
C
C
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000009:adverse effects*; D002117:Calcitriol / Q000627:therapeutic use; D002118:Calcium / Q000097:blood; D002136:Calcium, Dietary / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced* / Q000188:drug therapy; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011832:Radiation Injuries / Q000517:prevention & control; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*
D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D002117:Calcitriol; D004999:Amifostine; D002945:Cisplatin; D002118:Calcium