Chemotherapy and Immunotherapy

what is immunotherapy?

Immunotherapy generally involves treatments that are designed to help the immune system better recognize and attack cancer cells. Currently, these treatment are predominantly a class of medications called immune-checkpoint inhibitors. One way cancers grow is by escaping the normal mechanisms that the immune system uses to clear damaged/bad cells. The immune system has checkpoints, or brakes, that are present to help prevent it from being overactive. Checkpoint inhibitors remove these brakes and let the immune system be more active and clear the damaged cell. This can help to also create memory T-cells that may continue to recognize and react to the cancer cells even after treatments have been completed. Currently, all of these treatments are given intravenously. The most common types are called PDL1/PD1 inhibitors, and include nivolumab (Opdivo), pembrolizumab (Keytruda) and cemiplimab (Libtayo). For squamous cell carcinomas of the head and neck, these are given in patients that have relapsed and/or metastatic disease that are not candidates for further surgery or radiation. They are often given in combination with chemotherapy. For cutaneous squamous cell carcinomas (primary skin cancers), these may be given in patients with recurrent disease again when surgery and radiation are not options. For patients with melanomas, these may be given to high-risk patient post operatively or in patients with metastatic disease. In that situation, another common treatment is combined immunotherapy with nivolumab and ipilimumab (Yervoy).

The side effects of immunotherapy are primarily related to the autoimmune toxicities that occur by allowing the immune system to be more active. The most common of these are rash if the immune system attacks the skin and diarrhea if it attacks the colon. However, since the immune system is active throughout the body, multiple systems can be affected including pituitary, thyroid, heart, lungs, kidneys, liver, pancreas, adrenals, and joints. Many patients can be supported with less aggressive interventions like imodium or topical steroids. However, some may require steroids to help suppress the immune system or even discontinuation of the medication.

What is targeted therapy?

The most common targeted therapy used in treatment of head and neck cancer is cetuximab (Erbitux). This is a medication known as a monoclonal antibody that targets a receptor on the surface of the cells called endothelial growth factor receptor (EGFR). It is most often given in combination with radiation treatments, but is also frequently given in late-stage cancers in combination with other chemotherapies or sometimes by itself. It is most often given intravenously on a weekly basis. Common side effects include fatigue, skin rash (similar to acne) oninf the face and chest, and decreases in magnesium levels, which require IV infusions to replace.

There are also targeted therapies used in treatment of patients with melanoma who have a BRAF mutation in their cancer cells. This treatment is given by pill, and typically consists of two different medications, one targeting BRAF and the other targeting MEC. There are several similar drugs available and the choice is primarily based on individual preferences. These are most often used in patients with Stage IV melanomas, but may also be recommended for some patients post-operatively that are deemed to be at higher risk of recurrence. Side effects include mouth sores, fever, diarrhea, rash, and small risk of non-melanoma skin cancers. A less commonly used targeted therapy for advanced basal cell skin cancers are the hedgehog inhibitors, vesmodigib (Erivedge) and sonidegib (Odomzo). These are oral medications that target the hedgehog pathway. Side effects include muscle spasms, hair loss, nausea, rash, and other skin cancers.

While not technically chemotherapy, the third common type of targeted therapy is used in patients with thyroid cancer. After surgery, patients are placed on thyroid replacement therapy (typically levothyroxine) which is use both to replace missing thyroid hormone and to suppress production of thyroid stimulating hormone (TSH) by the pituitary gland. This is to prevent TSH from stimulating any residual cancer cells. Side effects of thyroid replacement therapy can include palpitations, weight loss, and decreased bone density. Some patients with thyroid cancer that has metastasized are treated with BRAF inhibitors as well, as above.

managing side effects of platinum-based chemotherapy (cis-platin, carbo-platin, “platinol”)

In a practical sense, the key to getting through platinum based chemotherapy is a matter of determination and remembering that while the treatment feels like it is kicking your butt, it’s kicking cancer’s butt even more. As for limiting specific side effects, your individual care will be through your medical oncologist, and may consist of the following:

• Nausea is treated with medication (like ondansetron and corticosteroids). Since nausea can lead to decreased fluid intake, I.V. rehydration may be used from time to time.

• Kidney damage is limited by staying hydrated. Since head and neck cancer and its treatments can affect swallowing, and since nausea can also limit fluid intake, the key is to stay as well-hydrated as possible and use I.V. rehydration when needed.

• Inner ear damage (hearing loss, tinnitus) is common, but of variable extent from one patient to another. Recent data suggests that a lower dose of platinum-based therapy given once a week may have less inner ear injury than a higher dose given every three weeks, without compromising the effect on cancer treatment. Hearing tests (audiograms) are usually performed before chemotherapy is begun and mid-way through the treatment course. If hearing is significantly worse, the medical oncologist may decide to change from cis-platin carboplatin (or vice-versa), as each affects inner ear cells slightly differently, and the change can spread the burden of toxicity. Hearing aids and possibly some balance therapy are helpful after treatment is complete for patients who lost some hearing and/or balance.

Also, be aware that platinum-based chemotherapy is typically used with radiation therapy, and so one should consider the treatment effects of radiation as well.