Cisplatin-induced vomiting depends on circadian timing

Area of Science:

• Oncology
• Pharmacology
• Nephrology

Background:

• Cisplatin is a cornerstone chemotherapy agent for various cancers.
• Cisplatin administration can cause significant nausea, vomiting, and renal toxicity.
• The optimal timing for administering cisplatin and supportive care is not well-established.

Purpose of the Study:

• To investigate the impact of administration timing (morning vs. evening) of cisplatin, furosemide, and ondansetron on chemotherapy-induced emesis and renal toxicity.
• To determine if ondansetron's timing influences the effect of cisplatin administration on emesis.
• To assess the influence of cisplatin and furosemide administration time on renal function markers.

Main Methods:

• A crossover study design was used with 22 urogenital cancer patients receiving two chemotherapy courses.
• Cisplatin and furosemide were administered in the morning (05:00) or evening (17:00) in a randomized sequence.
• Nausea, vomiting episodes, serum creatinine, BUN, creatinine clearance, and urinary NAG were monitored before and after treatment.

Main Results:

• Morning cisplatin administration was associated with more vomiting in the first course, but prophylactic ondansetron reduced this time-of-day effect.
• Renal toxicity, indicated by increased urinary NAG, was lower with morning cisplatin and furosemide administration compared to evening administration, particularly in the second course.
• Serum creatinine levels showed a transient decrease post-treatment, with a notable rise in the second course only for patients receiving evening cisplatin and furosemide.

Conclusions:

• The timing of cisplatin administration impacts emesis, though prophylactic ondansetron mitigates this.
• Morning administration of cisplatin and furosemide may reduce cisplatin-induced renal toxicity.
• Optimizing administration timing and supportive care, including hydration and furosemide, could improve cisplatin tolerability.