Oncology Pharmacist Explains Kidney Cancer Side Effect Management

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This is a guest post by Julia Stevens, PharmD, BCOP at Beth Israel Deaconess Medical Center in Boston, Massachusetts and a member of the Kidney Cancer Association’s Clinical Advisory Board.

Case Study: Jan’s Angelic Voice Got Lost in Kidney Cancer Treatment

My patient Jan was a vibrant 60-something year old woman diagnosed with metastatic renal cell carcinoma. The first time I met her, she and her family impressed me with their kindness and love for each other. She started axitinib (Inlyta) + pembrolizumab (Keytruda) and fortunately her cancer shrank over the next few scans. Over time some of her side effects became manageable with dose adjustments and supportive agents, but one side effect lingered: voice hoarseness (also called dysphonia). Speaking above a whisper took effort and sounded squeaky. Not one to complain, Jan bore the burden of losing her voice for several months. Only after she passed would I discover that she was a professional auctioneer by trade, known to her family and friends for having the voice of an angel. 

Kidney cancer and the treatments for it can cause a variety of side effects that vary in intensity, from a medical perspective. But side effects can also have a unique impact on a patient’s quality of life. In Jan’s case, her voice was central to her identity and, though mild, the dysphonia likely had an outsized impact on her overall wellbeing.

Below, I will explain how care providers like me approach managing some common kidney cancer-related side effects. Hopefully, this will help you understand any side effects you may be having and work with your care team to manage them so that you have the best quality of life possible.

What is a Side Effect “Grade”?

Clinical trials studying new drugs measure side effects – sometimes called adverse events (AE) – using guidelines from the National Cancer Institute Cancer Therapy Evaluation Program (NCI CTEP), called the Common Terminology Criteria for Adverse Events (CTCAE). At each appointment, a member of the clinical trial study team, usually a research nurse, will ask the patient to rate side effects of the medication(s) they are receiving. The research nurse then translates the severity of these side effects described by the patient into grades based on CTCAE criteria, from grade 1 (mild) to grade 5 (death). A side effect is generally considered to be “severe” at grade 3 or higher. The example CTCAE Criteria table below details how to grade the severity of diarrhea, a common side effect of kidney cancer treatment, based on what is happening to the patient.  

Common Terminology Criteria for Adverse Events (CTCAE) Criteria: Diarrhea 

Grade	Description	Example
Grade 1	Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.	Change in stool consistency or frequency.
Grade 2	Moderate; minimal, local or noninvasive intervention indicated; limiting instrumental ADL.	Increase of 4 – 6 stools per day over baseline; change in consistency or frequency AND limiting instrumental activities of daily living (ADLs)
Grade 3	Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.	Increase of 7 or more stools per day over baseline; hospitalization indicated; requires IV intervention; limiting self-care ADLs
Grade 4	Life-threatening consequences; urgent intervention indicated.	Life-threatening consequences; urgent intervention indicated
Grade 5	Death related to AE	Death

The approach to managing a side effect varies dramatically based on the drug causing the issue, the specific side effect, and patient-specific factors. Generally speaking, grade 1 side effects typically require no change in treatment, whereas grade 2 side effects may require some kind of support, such as prescribing a medication or treatment to help manage the specific issue. The recommendation for most drugs is to stop the medication at least temporarily (usually for several days to a few weeks) for grade 3-4 side effects. Severe side effects frequently require hospital admission for intensive support.  

These grading criteria are incredibly helpful for doctors and patients to understand the potential side effects of a newly approved treatment and to standardize management of those side effects — 50% of patients having grade 1 diarrhea might be a manageable threshold, but 50% of patients being admitted to the hospital for diarrhea is another thing entirely and warrants more monitoring and support. However, grade 1-2 side effects can still have a negative impact on a patient’s physical and mental health even if they are not life-threatening. “Annoying” or non-life-threatening side effects can still erode patients’ identity and affect their daily life and relationships. This might be particularly true for drugs that patients take for several months or years. CTCAE criteria do not take into account how long a patient is living with a given side effect, nor how bothersome it is to the patient.  

Looking Beyond Grade – When Mild Side Effects Make a Big Impact  

Fatigue is a common issue experienced by patients with cancer. Fatigue can stem from many potential causes, among them both cancer itself and cancer treatments. Fatigue that is relieved by rest is a grade 1 side effect. However, many people do not have the ability to add more rest or naps to their routine! Even grade 1 fatigue can affect work, family, relationships, and daily life. I have had many patients whose families or bosses had to recalibrate their expectations for their productivity and involvement—some with more understanding or more frustration than others. Fatigue may prompt other changes in life and daily routines that can add stress, affect productivity, or strain relationships.  

Immune system-activating drugs such as pembrolizumab (Keytruda) and nivolumab (Opdivo) are proven effective for multiple types of kidney cancer in different combinations. One of the common mild side effects of immune therapy is a slow or sluggish thyroid (hypothyroidism). If hypothyroidism does occur, it typically requires lifelong thyroid hormone replacement with a daily pill (grade 2 hypothyroidism). For most patients, this is a small price to pay for cancer control. However, I have spoken with patients who did not realize that this side effect was not reversible and who resented the daily reminder of their cancer diagnosis and treatment.  

Change in taste (dysgeusia) is another common side effect of some cancer treatments. Patients may find that foods taste salty, metallic, or less flavorful. Although the primary medical concern is avoiding weight loss due to dysgeusia, many patients feel that taste changes make eating feel like a chore. Ensuring that a patient eats enough despite low appetite or taste changes can become a source of tension between patients and their caregivers. Some people may be uniquely affected—one of my patients was a chef and his dysgeusia affected his job performance and livelihood.  

Although most people with kidney cancer have no outward signs of their condition, some side effects may become visible to others. For example, drugs such as cabozantinib (Cabometyx) and lenvatinib (Lenvima) can cause hair thinning or greying over time. Although medically unconcerning, many patients find this upsetting as they prefer to selectively disclose their diagnosis and take great lengths to prevent outward symptoms. Body image concerns can significantly contribute to cancer-related distress.  

Patients sometimes hesitate to share the personal ways that treatment is impacting them. These side effects are more subjective. Patients may feel that these impacts are too embarrassing or too trivial to discuss with their providers. Furthermore, many patients are understandably more worried about effectively treating their cancer than minimizing the impact of side effects—they may fear that their providers will less aggressively treat their cancer if they share the full picture of their side effect severity. It does not help that many providers are often not asking additional questions to assess the impact on a patient’s wellbeing and daily life. However, minimizing side effects does not necessarily come with less aggressive cancer treatment. 

Preparing Before Treatment 

Questions to Ask Your Healthcare Team

Asking your provider the following questions can give you a better understanding of the potential risks of treatment:

• What are both the more common and the more rare side effects?  

• When do side effects typically happen?  

• How can you help me if a side effect happens?  

• Would this side effect go away if we decided to stop the treatment? How long would it take to go away? 

• What can I do to prevent side effects? 

• How much do these side effects typically affect day-to-day life? 

With this information, you are better equipped to make decisions about your life, work, relationships, and responsibilities while on treatment. You can also better advocate for yourself if a side effect does occur.

Communicating While on Treatment 

It is helpful for patients and caregivers to keep note of the symptoms and side effects they experience. Some patients do this in an app on their phone, others keep a simple electronic or physical journal. When recording your symptoms, note how frequent and how severe the symptoms are. For example, the number of diarrhea episodes per day is an important factor, as well as the presence of abdominal pain or blood in the stool. Also consider noting how the symptoms impact your daily routine, time, productivity, and relationships.  

If a symptom is impacting your life, please communicate that with your team! Your providers will only know about these effects from you. You may decide with your team not to make any changes to your treatment plan, but there might be options out there that better balance treating cancer with minimizing side effects.  

Case Closing: Learning From Jan’s Story 

Jan and her family mentioned her hoarse, squeaky voice during her visits. It seemed to be grade 2 and we had limited meaningful suggestions to improve her voice. In our view, her dysphonia was mild enough that we did not discuss the one real option: switching to another similar medication that might have less dysphonia. Now that I know how central her unique voice was to her identity, I wonder if the conversation could have gone differently. Perhaps Jan would have decided to continue on axitinib (Inlyta). Perhaps she would have wanted to switch. Maybe we could have saved her and her family this constant reminder of her illness. At the very least, we could have acknowledged the impact that dysphonia was having on her life, relationships, and identity.  

Acknowledgements  

Thank you to Amy Marbaugh, RN and KCA’s Senior Director of Patient Programs, Virginia Seery, NP and member of KCA’s Clinical Advisory Board, and David Einstein, MD at Beth Israel Deaconess Medical Center for their invaluable feedback.