After living with an ovarian cancer diagnosis for 2 years, a 64-year-old patient turned to the chemotherapy drugs liposomal doxorubicin and carboplatin in hopes of slowing the cancer’s progression. Less than 2 months later, she reported the appearance of erythema (redness), ulceration, and exudation (fluid oozing from the skin) on her back, hands, and feet.

This patient ultimately learned she had hand-foot syndrome (HFS)—a side effect of some chemotherapy treatments.

 

Chemotherapy side effect

HFS, which is also called palmar-plantar erythrodysesthesia and Burgdorf’s syndrome, is a side effect of certain chemotherapy drugs.

According to an article published by Oncology Reviews, HFS symptoms kick off with palmoplantar (palms and soles) numbness, burning pain, or tingling.

Kwakman JJM, Elshot YS, Punt CJA, et al. Management of cytotoxic chemotherapy-induced hand-foot syndrome. Oncol Rev. 2020;14(1):442.

 

HFS targets the hands and feet—which is likely how the syndrome earned its name. These symptoms occur alongside well-defined redness that may or may not include edema, desquamation, or cracking.

As HFS progresses, patients who have it can experience ulceration and blistering. Patients of color may notice macular hyperpigmentation in place of erythema.

 

Which drugs induce HFS?

Research has shown that pegylated liposomal doxorubicin (PLD), which is used to treat breast and ovarian cancers, docetaxel (used to treat breast, gastric, prostate, non-small cell lung, and head and neck cancer), and fluoropyrimidines (used to treat solid tumor types) including intravenous 5-fluorouracil (5-FU), capecitabine, and S-1 are often to blame.

Patients are more likely to develop HFS if they take these treatments on a continuous dosing schedule, or if their medication (such as capecitabine) has high blood serum levels.

Little is known about the pathogenesis of HFS, but its side effects may differ based on the medication that triggers it. Symptoms usually show up with repeated use of the above-named drugs, and decrease once the treatments are discontinued.

Ultimately, HFS is not life-threatening—but it can severely impact a patient’s quality of life.

 

HFS prevalence and diagnostics

HFS is relatively common. Oncology Reviews states that different drugs have varying rates of incidence. For example, between 2.6% and 18% of patients who take intravenous 5-FU in phase three trials report the development of HFS symptoms.

Capecitabine, on the other hand, shows up in 22% to 77% of patients in the same trial phase. When taken in combination with pegylated liposomal doxorubicin, that incidence rate coasts at 39%. PLD alone tends to cause HFS in as much as 48% of patients with metastatic breast cancer.

While further research is needed to confirm rates of HFS among patients who take Docetaxel, some evidence shows that any grade of HFS may surface in about 40% to 53% of patients who take generic Docetaxel products.

The 64-year-old patient with ovarian cancer, for example, was initially diagnosed with Tinea corporis, commonly referred to as ringworm infection and prescribed calamine lotion and terbinafine cream. Only when that treatment failed did her doctors consider HFS a possibility, according to a case report published by the Journal of International Medical Research.

Ni C, Fang J, Qian H, et al. Liposomal doxorubicin-related palmar-plantar erythrodysesthesia (hand–foot syndrome): a case report. J Int Med Res. 2020;48(12):030006052097485.

 

Clinicians should therefore keep in mind each potential diagnosis that may apply when a patient starts showing symptoms of HFS and take into consideration the patient’s cancer history and medication history.

 

How to manage HFS

An article published by Breastcancer.org offers the following prevention tips:

Hand-foot syndrome (HFS) or palmar-plantar erythrodysesthesia (PPE). Breastcancer.org. Updated February 22, 2022.

 

• Limit heat exposure on hands and feet

• Relieve your hands and feet of pressure

• Take breaks from exercise

• Avoid use of knives, screwdrivers, hammers, and gardening tools

By implementing these tips, patients reduce the risk of chemotherapy leakage through their skin and the subsequent development of HFS.

If HFS is already present, the Oncology Reviews article suggested that clinicians consider lowering the medication dose—although this may lead to other undesirable effects—or switch to a similar medication that has a lesser association with HFS.

Finally, topical treatments, including prophylactic use of urea-based cream, may help soothe patients’ symptoms.