Medical Pharmacology Practice Questions: Chapter 33-34 Inhibitors of Cyclin Dependent Kinases 4/6: Palbociclib (Ibrance)

Medical Pharmacology Practice Questions: Inhibitors of Cyclin Dependent Kinases 4/6: Palbociclib (Ibrance), Ribociclib (Kisquali), Abemaciclib (Verzenio)

Cyclin-dependent kinase (CDKs) are involved in regulating signaling associated with cell-cycle progression.
1. True
2. False
CDK4/6 are targeted by anticancer agents given that these cyclin -dependent kinases control cell-cycle transition from G0/G1 to the S phase.
1. True
2. False
The class of CDK inhibitory agents may be identified by their ending, ciclib, such as in palbociclib (Ibrance).
1. True
2. Falls
Palbociclib:
1. Orally bioavailable
2. Inhibits CDK4
3. Inhibits CDK6
4. A & B
5. B & C
6. A & C
7. A, B & C
Palbociclib pharmacokinetic/pharmacodynamics:
1. Half-life is about one day
2. Palbociclib is metabolized by the cytochrome P450 drug metabolizing system, particularly CYP3A4.
3. Palbociclib is both a substrate at an inhibitor of CYP3A4.
4. A & B
5. B & C
6. A & C
7. A, B & C
Palbociclib is metabolized by sulfotransferase (SULT2A1), phase II metabolism.
1. True
Clinical/therapeutic use(s) of palbociclib:
1. Treatment of advanced or metastatic breast cancer exhibiting ER positivity and HER2 negativity.
2. Palbociclib in combination with letrozole (aromatase inhibitor) as endocrine-based treatment in postmenopausal women.
3. Both
4. Neither
Palbociclib may be combined with the estrogen receptor antagonist fulvestrant for management of metastatic breast cancer which has progressed during endocrine monotherapy.
1. True
2. False
Compared with letrozole alone, the combination of palbociclib and letrozole in treating metastatic breast cancer is associated with progression free survival of up to a median of two years (compared to one year, letrozole alone).
1. True
2. False
Among the mostcommon adverse effect(s) of palbociclib administration include/includes:
1. Neutropenia
2. Leukopenia
3. Both
4. Neither
Palbociclib should not be administered in combination of a strong CYP3A inhibitor (many drugs fall into this category) as this combination predisposes to increased palbociclib exposure to the patient. If such coadministration is not possible, reduction in the dose of palbociclib may be a necessity.
1. True
2. False
Coadministration of a strong CYP3A inducer would tend to:
1. Decrease patient exposure to palbociclib
2. Increase patient exposure to palbociclib
Which one(s) of the following agents are CDK4/6 inhibitors with inhibitory characteristics comparable to that of palbociclib.
1. Abemaciclib (Verzenio)
2. Ribociclib (Kisqali)
3. Both
4. Neither
Abemaciclib:
1. Compared to the other cyclin4/6 inhibitors, exhibits higher affinity for CDK4.
2. Effective, positive disease control (and clinical trials) are noted when Abemaciclib is combined with letrozole or anastrazole (aromatase inhibitors) or tamoxifen (antiestrogen).
3. Both
4. Neither
Abemaciclib metabolism primarily involves the cytochrome P450 drug metabolizing system, particularly the CYP3A4 isoform.
1. True
2. False
Compared to palbociclib and ribociclib, abemaciclib appears to cause:
1. Less neutropenia
2. More diarrhea risk
3. Both
4. Neither
Clinical use/uses for abemaciclib:
1. As monotherapy: for treatment of HR -positive, HER2-negative advanced or metastatic breast cancer in those patients exhibiting progressive disease after Endocring treatment and prior chemotherapy (metastatic).
2. In combination with fulvestrant: for treatment of HR -positive HER2-negative (negative for human epidermal growth factor receptor 2) metastatic breast cancer exhibiting progressive disease despite Endocring treatment.
3. Initial Landgren-based treatment (combined with aromatase inhibitor) for treating hormone receptor (HR) -positive, HER2 negative advanced or metastatic breast cancer (postmenopausal women).
4. A & B
5. B & C
6. A & C
7. A, B & C
"The FDA has approved new warnings for cyclin -dependent kinase (CDK) 4/6 inhibitors-Ibrance (palbociclib), Kisqali (ribociclib), and Verzenio (abemaciclib)-concerning the risk of interstitial lung disease (ILD) and/or pneumonitis. Healthcare providers should monitor patients regularly for pulmonary symptoms indicative of ILD and/or pneumonitis. Patients with new or worsening respiratory symptoms should have treatment interrupted for further evaluation. Patients found to have severe ILD or pneumonitis should have CDK4/6 therapy permanently discontinued."
1. True
2. False
Ribociclib (Kisqali):
1. Small-molecule cyclin -dependent kinase inhibitor, selected for CDK4/6.
2. Inhibits retinoblastoma protein phosphorylation, preventing cell-cycle progression.
3. Both
4. Neither
Combined treatment involving ribociclib and an aromatase inhibitor such as fulvestrant appears to reduce tumor growth in estrogen receptor positive breast cancer
1. True
2. False
Ribociclib: pharmacokinetics
1. Primarily hepatic metabolism (CYP3A4)
2. Terminal half-life elimination (final phase of multiphase elimination profile) is about 30-60 hours.
3. Both
4. Neither