Few therapies are effective for treating advanced soft tissue sarcoma (STS), so pazopanib quickly became a commonly prescribed therapy once it was approved for STS in April 2012. Although pazopanib is safe and effective, patients must be educated about its administration and side effects.
In their article in the June 2015 issue of the Clinical Journal of Oncology Nursing, Holland and Flaherty identified the key educational needs of patients receiving oral pazopanib for STS and surveyed a group of oncology nurses to determine whether standardization of patient education was necessary.
Pazopanib for Soft Tissue Sarcoma
Pazopanib is a multitargeted tyrosine kinase inhibitor (TKI) that works against vascular endotheial growth factor (VEGF), platelet-derived growth factor, and c-kit, Holland and Flaherty explained. TKIs like pazopanib have a mechanism of action in competitive adenosine triphosphate inhibition at the catalytic binding site of tyrosine kinase. Pazopanib also prevents angiogenesis by inhibiting VEGF receptors and limiting the vascular supply to the tumor, which stunts growth.
Because of how pazopanib is metabolized, many other commonly prescribed medications may affect dosing. Pazopanib uses the cytochrome P450 (CYP3A4) enzymes, so patients must avoid strong CYP3A4 inhibitors and inducers. If a CYP3A4 inhibitor is unavoidable (e.g., clarithromycin), the pazopanib dose may need to be reduced to prevent too much of the drug being metabolized. In contrast, CYP3A4 inducers (e.g., dexamethasone) can reduce concentrations of pazopanib, making treatment less effective. Oncology nurses should reconcile medications with patients to identify potential drug interactions and ask patients to alert their providers if their medications change.
Nurses and patients also need to understand that because of pazopanib’s hepatic metabolism, a liver function test baseline will be established and then monitored on a serial basis to watch for elevated liver enzymes. Holland and Flaherty noted that pazopanib has minimal renal metabolism, so patients with renal impairment can take the drug without dose modifications.
Because pazopanib inhibits angiogenesis, patients who require surgery (including dental work) will need to stop the drug seven days before their procedure so they can experience optimal blood flow to the surgical site to help with wound healing. After their surgery, the drug can be resumed based on instructions from the prescribing oncologist.
Patients should be instructed to take pazopanib on an empty stomach, either one hour before or two hours after a meal. The drug’s absorption is increased with food, and patients could be at risk for more serious adverse events if too much drug is absorbed.
Managing Pazopanib’s Side Effects
According to Holland and Flaherty, the most common adverse reactions to pazopanib in patients with advanced STS are diarrhea, hypertension, and nausea and vomiting. They noted that pazopanib is also approved for patients with renal cell carcinoma, and the side effects of the drug have different severity in that population.
Diarrhea: Diarrhea from pazopanib is commonly mild to moderate in severity, and patient education involves instruction on self-management of mild diarrhea and when to call if diarrhea becomes moderate or severe.
“Grade 1 (mild) diarrhea is four stools per day over baseline, grade 2 (moderate) is four to six stools per day over baseline, and grade 3 (severe) is more than seven stools per day over baseline, incontinence, hospitalization indicated, or limiting self-care activities of daily living,” according to Holland and Flaherty. Nurses should instruct patients to call their healthcare provider if they experience more than four stools over baseline. Management involves oral rehydration, nutrition, antimobility medications, antisecretory agents, absorbents, and antimicrobials.
Hypertension: Holland and Flaherty explained that all VEGF inhibitors, including pazopanib, can cause hypertension because of how they work: they decrease the number of capillaries and arterioles throughout the body to reduce blood flow to a tumor. They also can cause arterial stiffness and increased vascular resistance because of reduced nitric oxide and prostacyclin production.
Candidates for pazopanib therapy should be screened for prehypertension (systolic blood pressure [SBP] of 120–139 mmHg; diastolic blood pressure [DBP] of 80–89 mmHg) and undiagnosed hypertension. If hypertension develops, it’s usually early in treatment: 40% of cases appear by day 9, and 90% appear within the first 18 weeks.
Nurses should take a baseline blood pressure before initiation of therapy, and patients should be instructed to monitor their blood pressure frequently (daily to several times per week). Patients with a history of hypertension, poor hypertensive control, or other cardiovascular comorbidities should monitor on the higher frequency end of that range.
In cases of grade 3 hypertension (SBP of 180 mmHg or higher; DBP of 110 mmHg), patients should receive additional antihypertensive agents or increased doses of antihypertensive drugs they are already taking.
Nausea and vomiting: Pazopanib causes nausea in more than 50% of patients with advanced STS; however, the risk for emesis is lower at approximately 33%. Holland and Flaherty noted that nausea in particular has a discrepancy in rates among patients with STS and patients with renal cell carcinoma, with the rates in STS considerably higher.
Because nausea is so prevalent with pazopanib, nurses should prepare patients to expect this side effect. They should educate patients on the dose and schedule of any prescribed antiemetics, dietary recommendations for managing nausea, and information about nonpharmaceutical techniques (e.g., meditation, acupressure) for persistent nausea. Nurses should instruct patients to call if their nausea is not well controlled.
For more information on managing the common side effects of pazopanib in patients with advanced STS, as well as the results of the survey Holland and Flaherty conducted to determine the necessity of standardized patient education in their institution, refer to the full article in the Clinical Journal of Oncology Nursing.
Five-Minute In-Service is a monthly feature that offers readers a concise recap of full-length articles published in the Clinical Journal of Oncology Nursing (CJON) or Oncology Nursing Forum. This edition summarizes “Nursing Considerations for Patients With Sarcoma on Pazopanib Therapy,” by Jessie Holland, BSN, RN, OCN®, and Catherine Flaherty, BSN, RN, OCN®, which was featured in the June 2015 issue of CJON. Questions regarding the information presented in this Five-Minute In-Service should be directed to the CJON editor at CJONEditor@ons.org. Photocopying of this article for educational purposes and group discussion is permitted.