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Toxicities Associated With PARP Inhibitors for Ovarian Cancer

By: Melissa E. Fryman, MS
Posted: Monday, February 4, 2019

The myriad benefits and relative risks of PARP inhibitors were explored by Christopher J. LaFargue, MD; Graziela Z Dal Molin, MD; and colleagues, of The University of Texas MD Anderson Cancer Center, in a review published in The Lancet Oncology. The authors cautioned that “individual PARP inhibitors have unique adverse events that require a thorough understanding of the specific toxicities, as well as knowledge regarding monitoring and dose regimen customization.”

“Appropriate counseling should be provided before starting treatment to manage the expectations of both patients and caregivers to prevent treatment interruption or premature discontinuation,” they recommended.

The three PARP inhibitors that have been approved by the U.S. Food and Drug Administration for the treatment of recurrent epithelial ovarian cancer—olaparib, niraparib, and rucaparib—have a unique mechanism of action, targeting cells with homologous recombination deficiency. Their treatment indications partially overlap, although their toxicity profiles may vary substantially.

Some adverse events associated with PARP inhibitors may be predictable, with class effects such as hematologic toxicities and fatigue being the most common. Gastrointestinal and renal toxicities are also common, and hypercholesterolemia and increased serum aminotransferase may be associated with PARP inhibitors. Less commonly, neurologic, respiratory, musculoskeletal, cutaneous, and cardiovascular toxicities may be seen with this class of drugs. Secondary malignancies, although rare, are possible. Studies regarding definitive efficacy versus safety of PARP inhibitors in combination therapy are ongoing.

Timing of toxicity was also addressed by the investigators. “The majority of adverse events typically occur during the first cycles of treatment. and patients should be closely monitored during this time,” they suggested.

Disclosure: The study authors’ disclosure information may be found at thelancet.com.



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