Acute severe hypokalemia caused by treatment of tongue squamous cell carcinoma with docetaxel and cisplatin: A case report

Abstract

BACKGROUND

The tongue squamous cell carcinoma (TSCC) is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa, characterized by a high malignant degree, invasive growth, early lymph node metastasis, and poor prognosis. Paclitaxel, represented by docetaxel, is now the standard first-line treatment for head and neck squamous cell carcinoma. Docetaxel, which belongs to the class of drugs known as paclitaxel, is an antitumor drug that inhibits cell mitosis and proliferation. Its adverse effects include myelosuppression, hair loss, gastrointestinal reactions, fluid retention, and allergic reactions. However, hypokalemia is rare, most cases are mild or moderate, and severe hypokalemia is seldom reported.

CASE SUMMARY

During chemotherapy with docetaxel and cisplatin, a patient with TSCC developed severe hypokalemia. His potassium level was found to have been reduced to 1.85 mmol/L at the most critical situation. The patient had grade 1 muscle strength in all four limbs and could not perform any action, which was considered to be a sign of severe hypokalemia. Measures taken included intravenous infusion via micro-pump, intravenous injection, and oral potassium supplement, which gradually improved muscle strength and serum potassium levels. The patient survived the critical period of severe hypokalemia after chemotherapy. He was generally in good condition following treatment and discharged in stable condition.

CONCLUSION

Docetaxel may cause severe hypokalemia with hypomagnesemia and the mechanism for this is not yet known to researchers yet. This means that nurses specializing in chemotherapy must exercise a high degree of responsibility, closely observe the patient’s reaction to the anticancer medication, notice any symptoms of adverse effects early. It is necessary to be considerate regarding individual differences between patients when selecting chemotherapy regimens and adhere to the principle of individualized treatment. Following multiple cycles of chemotherapy, patients should be aware of the accumulation of toxic side effects and receive blood tests reviewed within 24 hours of completion. It is essential to monitor electrolyte levels in patients suffering from severe gastrointestinal reactions to avoid complications that may result in death.

Key Words: Tongue squamous cell carcinoma; Docetaxel; Hypokalemia; Hypomagnesemia; Case report

Core Tip: The patient with tongue squamous cell carcinoma who had severe hypokalemia combined with hypomagnesaemia on the third cycle of docetaxel combined with cisplatin chemotherapy, and recovered to normal after active potassium supplementation and other measures. After analysis, it was considered that the occurrence of hypokalemia in this patient may be related to docetaxel therapy, and docetaxel may cause increased potassium ion (K⁺) transfer into the cell, but the mechanism is still unclear. We hope to get the attention of peers through this case: For example, mechanistic studies of whether docetaxel might increase K⁺ to intracellular transfer, and healthy care should pay attention to any complaints and discomfort symptoms during the process of chemotherapy from cancer patients.

INTRODUCTION

The tongue squamous cell carcinoma (TSCC) is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa, characterized by a high malignant degree, invasive growth, early lymph node metastasis, and poor prognosis. Paclitaxel, represented by docetaxel, is now the standard first-line treatment for head and neck squamous cell carcinoma. The patient with TSCC who had severe hypokalemia combined with hypomagnesaemia on the third cycle of docetaxel combined with cisplatin chemotherapy, and recovered to normal after active potassium supplementation and other measures. After analysis, it was considered that the occurrence of hypokalemia in this patient may be related to docetaxel therapy, and docetaxel may cause increased potassium ion (K⁺) transfer into the cell, but the mechanism is still unclear. Mechanistic studies of whether docetaxel might increase K⁺ to intracellular transfer should be gave more attention and nurses specializing in chemotherapy must exercise a high degree of responsibility, closely observe the patient’s reaction to the anticancer medication, notice any symptoms of adverse effects early, and inform the physician on time so that the patient can be promptly provided treatment for the same.

CASE PRESENTATION

Chief complaints

There was no apparent inducement for his dysphagia, aggravated by drinking alcohol and eating spicy food and accompanied by pharynx foreign body sensation for over six months.

History of present illness

In January 2022, the patient had swallowing pain without obvious inducement, and the pain was aggravated after drinking alcohol or eating spicy food. The patient did not pay attention to throat clearing accompanied by bloody secretions and foreign body sensation in the throat. In May 2022, the patient felt that swallowing pain was aggravated and accidentally felt a large and small lump of pigeon egg in the left mandible without tenderness and poor mobility, so he was treated with intravenous antibiotic infusion in a clinic in Nanning, Guangxi Province (infusion was 10 days, the specific drug was unknown), and symptoms repeated after withdrawal. On June 13, 2022, he was hospitalized in Dachuan District People’s Hospital, Sichuan Province, and underwent cervical lymph node biopsy and puncture. The examination indicated that “metastatic highly differentiated squamous cell carcinoma (left submaxillary lymph node)”. The patient was advised to conduct another biopsy to identify the primary focus. So he went to our hospital for further examination and treatment. In June 2022, the patient completed the specialized examination in the otolaryngology department of our hospital, he was diagnosed with left lingual squamous cell carcinoma (cT4aN2bM0, stage IV A) and secondary malignant tumors of the bilateral cervical lymph nodes. After evaluation by the oncologist, 3 cycles of neoadjuvant therapy were proposed and transferred from the ear, nose, and throat department to our department. On July 1, 2022, and July 22, 2022, the patient received two cycles of neoadjuvant therapy: He was administered with docetaxel injection (150 mg) for one day and cisplatin injection (75 mg) for two days [docetaxel and cisplatin (DP)]. On August 12, 2022, he suffered severe hypokalemia combined with hypomagnesaemia on the third cycle of docetaxel combined with cisplatin chemotherapy, who complained of general weakness, panic, and chest tight ness. The muscle strength was found to be grade 1 in the most severe stage in the lower extremities, and only muscle contractions were observed, no movement was possible. According to an emergency electrolyte measurement, the serum potassium level was reduced to 2.89 mmol/L. The potassium level at 11:10 on August 13 was were rechecked with the critical value of 1.85 mmol/L, in combination with a low serum magnesium level of 0.61 mmol/L.

History of past illness

The patient was previously healthy, with no history of chronic disease, infectious diseases, and also suffered no accidental trauma, except hypertension (previous maximum blood pressure 180/120 mmHg, take blood pressure drugs regularly, amlodipine-besylate 5 mg).

Personal and family history

His parents were alive, and brothers and sisters are also in good health. There are no diseases similar to the patient in the family, no diseases with genetic predisposition, no infectious diseases such as tuberculosis, hepatitis, and venereal diseases. He is married and has a pair of children.

The patient was born and had long lived locally, had a history of smoking (20 cigarettes/day, 20 years), had a history of drinking (200-300 mL/time, 20 years).

Physical examination

The skin and mucous membranes of the whole body were normal, and an enlarged lymph node of about 2.0 cm × 1.5 cm was palpable under the left jaw, with tough quality, poor mobility and no tenderness. A new creature at the base of the left tongue with a purulent substance on its surface. Mucosa erosion can be seen on the epiglottic tongue surface, no odor. Physical examination of the rest was normal.

Laboratory examinations

Upon admission and after discharge, the patient was in good health, and his vital signs were stable. Complete blood count tests, thyroid function tests, liver and kidney function tests, and electrolyte measurements did not reveal any significant abnormalities in the metabolism of potassium or magnesium Table 1 for electrolyte and liver and kidney function tests before and after admission.

Table 1 Changes of electrolytes before and after chemotherapy.

Detection index	Blood potassium/mmoL	Blood sodium/mmoL	Blood magnesium/mmoL
Prechemotherapy	4.2	141	-
Day 2 of chemo 22:04	2.89	142.4	-
Day 3 of chemo 11:10	1.85	143	-
Day 3 of chemo 16:30	2.06	142.6	0.61
Day 3 of chemo 20:30	2.83	-	-
Day 4 of chemo 9:39	4.51	141.8	1.04
Day 4 of chemo 16:22	4.72	-	0.93
Day 5 of chemo	4.39	-	-

Imaging examinations

After entering the otolaryngology department, a new biological biopsy was performed at the root of the left tongue under local anesthesia on June 24, 2022. The postoperative biopsy revealed squamous cell carcinoma at the root of the left tongue. Magnetic resonance imaging (craniocervical enhancement) examination suggested: (1) Laryngeal and pharyngeal space occupying lesions, combined with the history, laryngeal cancer was considered; and (2) Multiple swollen lymph nodes on both sides of the neck. Nuclear medicine showed: Irregular thickening of soft tissues in the left side wall of oropharynx, the left side wall of oral floor and the left side wall of laryngeal pharynx, abnormal increase of fluorodeoxyglucose metabolism, which was consistent with hypopharyngeal cancer.

FINAL DIAGNOSIS

The patient was diagnosed with left lingual squamous cell carcinoma (cT4aN2bM0, stage IV A) and secondary malignant tumors of the bilateral cervical lymph nodes.

TREATMENT

After evaluation by the oncologist, 3 cycles of neoadjuvant therapy were proposed for the original disease. Due to severe hypokalemia on the 3^rd cycle docetacel combined with cisplatin chemotherapy, the patient was immediately and simultaneously administered 1.5 g of potassium supplement intravenously through a micro-pump and 3 g orally on August 12. According to the serological findings, it was decided that the patient be administered supplements of potassium and magnesium. Within the next 24 hours, 1.5 g potassium was administered intravenously through a micro-pump, 3.7 g potassium was administered through intravenous infusion; a 12 g potassium chloride solution was divided into several parts, added to juice or milk several times, and taken orally; and 2.5 g magnesium sulfate was administered intravenously.

OUTCOME AND FOLLOW-UP

The serum potassium level was found to be 2.06 mmol/L at 16:30 on August 13. His muscle strength was found to have progressed to grade 2, and he could move his limbs parallel to the bed but could not resist gravity and lift them from the bed.

As of 20:30, the blood potassium level was found to be 2.83 mmol/L, muscle strength had recovered to grade 3, and he could lift his limbs off the bed but could not resist resistance. At 9:39 on August 14, the blood potassium was found to have returned to normal, with a value of 4.51 mmol/L. Muscle strength was found to be grade 5 and fully restored to normal. Serum magnesium levels had returned to normal, and the patient could move normally (The electrolyte changes of patients are shown in Table 1).

The patient successfully survived the critical period of severe hypokalemia after chemotherapy. Cisplatin was replaced with carboplatin to continue chemotherapy. Owing to the treatment, the patient’s general condition was found to be good, and he was discharged in stable condition.

DISCUSSION

Oral squamous cell carcinoma (OSCC) is the most common type of oral malignant tumor, and TSCC accounts for the highest proportion of OSCC[1]. The TSCC is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa and is characterized by a high malignant degree, invasive growth, early lymph node metastasis, and poor prognosis[2]. Direct surgical treatment may result in excessive injury to the maxillofacial area or the tumor may not be radically resected if it is found in a locally advanced stage at the time of diagnosis. Since the advances made in research on tumor biology in recent years, a comprehensive treatment regimen involving neoadjuvant chemotherapy and surgery combined with radiotherapy and chemotherapy has been demonstrated to have a curative effect in different types of locally advanced tumors[3,4]. Paclitaxel, represented by docetaxel, is now the standard first-line treatment for head and neck squamous cell carcinoma. Studies have demonstrated that docetaxel-based neoadjuvant therapy in combination with chemotherapy can improve organ preservation rates[5].

Many malignant tumors are treated clinically with docetaxel, an antineoplastic drug that causes several adverse reactions, including myelosuppression, hair loss, gastrointestinal reactions, fluid retention, and allergic reactions. Studies have shown that docetaxel can cause mild to moderate hypokalemia when combined with cisplatin[6] and afatinib[7], but the mechanism for this reaction is not yet known. Severe hypokalemia has rarely been reported. The patient, in this case, received neoadjuvant chemotherapy using the DP regimen and was found to be in partial remission, with the disease coming under control after two cycles. However, the patient developed severe hypokalemia and hypomagnesemia after the third cycle of chemotherapy. During the treatment period, the patient did not experience the symptoms of insufficient serum potassium and magnesium, such as a significant reduction in food intake, or those arising from excessive loss of potassium and magnesium, such as diarrhea, vomiting, or increased potassium levels in the urine. The patient responded actively with potassium supplementation and other treatments when there was a decrease in serum potassium levels. However, the serum potassium level still decreased, and the urine volume was normal, with reduced urine potassium, which contradicted the excessive potassium loss causing hypokalemia. At the time of his admission, the patient was in good health, and his vital signs were stable. Complete blood count tests, thyroid function tests, liver and kidney function tests, and electrolyte measurements did not reveal any significant abnormalities in the metabolism of potassium or magnesium. According to a few studies, hypokalemia has not been found to be associated with hypomagnesemia, but a deficiency in magnesium may decrease the activity of sodion-K⁺-adenosine triphosphatase and reduce K⁺ reabsorption, and a deficiency in K⁺ may cause hypokalemia. However, the patient’s urine potassium level was found to have decreased, with a value of 3.82 mmol/L, contrary to the increase in potassium excretion due to low magnesium levels. If the abnormal correlation between hypomagnesemia and hypokalemia is excluded, it is more likely that the patient suffered from severe hypokalemia and hypomagnesemia due to treatment with DP regimen.

In hypokalemia caused by drug treatment, more K⁺ may be transferred into cells. Hypokalemia can be induced by a number of drugs; antimicrobials, such as gentamicin and amikacin, for example, can impair the biological structure and function of the proximal tubule. This decreases the efficiency of potassium ion reabsorption, resulting in decreased concentration of potassium ions in the blood. The administration of amphotericin B[8] may lead to changes in the permeability of cell membranes and increased potassium absorption through the renal tubules, resulting in hypokalemia[9]. Analgesics, including acetaminophen, have been shown to cause severe hypokalemia[10]; High levels of metabolites of analgesics in the renal medulla may damage the epithelial cell membrane of the renal tubules, leading to renal papillary necrosis, chronic inflammation of the renal tubules, and distal renal tubular acidosis, which, in turn, leads to hypokalemia. However, the patient had not been taking any of these drugs. The antitumor drug cisplatin[11] has been shown to damage the epithelial cells in the renal tubules and increase magnesium excretion, causing renal potassium loss. The patient was not treated with cisplatin during the third cycle of chemotherapy, and the results of all tests conducted before this treatment were normal. Therefore, the side effects of cisplatin can be ruled out. Administration of high doses of dexamethasone for a prolonged period can cause toxic effects such as allergic shock, respiratory dyspnea, hypokalemia, and neurological problems. Previously, the patient had received dexamethasone for chemotherapy but had not developed hypokalemia. Prior to this chemotherapy, the patient was treated with 10 mg of dexamethasone, and he developed symptoms of hypokalemia following the administration of docetaxel. Since no symptoms of excessive potassium loss, such as vomiting or diarrhea, were observed, the severe hypokalemia in his case cannot be explained by the administration of 10 mg of dexamethasone alone.

CONCLUSION

When the patient, in this case, was on the third cycle of chemotherapy, he developed severe hypokalemia with hypomagnesemia occurring simultaneously, which may have been caused by docetaxel. Docetaxel is likely to increase the transfer of K⁺ into the cells, but the mechanism for this is not yet known. It is necessary to be considerate regarding individual differences between patients when selecting chemotherapy regimens and adhere to the principle of individualized treatment. Following multiple cycles of chemotherapy, patients should be aware of the accumulation of toxic side effects and receive blood tests reviewed within 24 hours of completion. It is essential to monitor electrolyte levels in patients suffering from severe gastrointestinal reactions to avoid complications that may result in death. The mechanism of how docetaxel causes hypokalemia and hypomagnesemia is not known to researchers yet, making it an important question in research on tumor biology. This means that nurses specializing in chemotherapy must exercise a high degree of responsibility, closely observe the patient’s reaction to the anticancer medication, notice any symptoms of adverse effects early, and inform the physician on time so that the patient can be promptly provided treatment for the same.