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© The Canadian Journal of Urology™; 23(Supplement 1); February 2016
Denosumab can cause symptomatic hypocalcemia.
Symptoms and signs of severe hypocalcemia include
altered mental status, tetany, seizures and QTc
prolongation. Pre-existing hypocalcemia should be
corrected prior to initiating therapy. While on therapy,
calcium levels should be monitored prior to the initial
dose of denosumab, within 2 weeks after the initial
dose, and if suspected symptoms of hypocalcemia
occur. Administer adequate calcium and vitamin D,
and magnesium, as necessary.
Osteonecrosis of the jaw (ONJ) has been reported in
patients treated with denosumab. ONJ can manifest
as jaw pain, osteomyelitis, osteitis, bone erosion,
tooth or periodontal infection, toothache, gingival
ulceration, or gingival erosion. Persistent pain or slow
healing of the mouth or jaw after dental surgery may
also be manifestations of ONJ. The incidence of ONJ
was higher with longer duration of exposure. Poor
oral hygiene, invasive dental procedures (e.g., tooth
extraction, dental implants, oral surgery), treatment
with anti-angiogenic medication, local gum or oral
infection are considered risk factors for ONJ in patients
receiving denosumab. Other risk factors for ONJ
include infections, older age, concomitant therapies
(e.g., chemotherapy, corticosteroids, radiotherapy to
the head and neck), smoking, and previous treatment
with bisphosphonates.
An examination of the oral cavity should be
performed by the prescriber prior to initiation of
denosumab treatment, and a dental examination with
appropriate preventive dentistry is recommended
prior to treatment with denosumab, especially in
patients with risk factors for ONJ. Good oral hygiene
practices should be maintained during therapy.
Patients should receive routine dental assessments,
and immediately report any oral symptoms such as
dental mobility, pain or swelling. While on treatment,
patients should avoid invasive dental procedures.
Summary
We have made tremendous advances over the last 70
years in managing first castration responsive and now
CRPC. These old and new therapies have performed
tremendously well in delaying the progression of
disease, improving the quality of life, and increasing
the survival in a significant number of men suffering
from aggressive prostate cancer.
As with any therapy that alters the normal
biochemistry and physiology of aman, there is a risk of
potential side effects. Some of these adverse effectsmay
aggravate the co-morbidities that the patient is already
exhibiting or cause problems that the primary care
physician is experienced in identifying and treating.
The primary care practitioner is also well versed in
managing the potential drug-drug interactions.
Even though the possible adverse effects of
established as well as newer pharmacologic therapies
in advanced prostate cancer are relatively infrequent,
there is an increasing demand for the urologist to
inform and partner closely with the primary care
physician to prevent, identify and assist in the
management of the potential side effects of these life
altering therapies.
Disclosure
Dr. Victor Mak has received speakers honoraria for
Abbott, Abbvie, Actavis, Allergan, Amgen, Astellas,
AstraZeneca, Ferring, Janssen, Norrizon, Novartis,
Pfizer, and Sanofi.
Dr. Jack Barkin is a speaker and investigator for Glaxo,
Actavis, Pfizer, Astellas, Merus Labs, Allergan, Janssen,
Ferring, NeoTract and Merck.
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The primary care physician’s role in the monitoring and management of the potential sequelae of the medical
treatment of prostate cancer: early and late