Alert for those on Tykerb--bring this up with your oncologist

[Lani]

I have read posts of those on Xeloda/Tykerb and even Tykerb alone complaining of diarrhea, nausea, fatigue, etc.

This article is about monoclonal antibodies against EGFR, which Tykerb is not, but as it acts on the internal portion of the same receptor, the effect may turn out to be the same.

I have made it a practice not to even seem to give advice and I certainly am not qualified to give advice , but I can't see the harm in asking to have your magnesium level tested if you are having complaints on Tykerb. Side effects of low magnesium can be serious as you can see below, so I can't imagine your oncologist not agreeing to the simple blood test.


Most Patients on Monoclonal Antibodies Suffer Magnesium Loss

Allison Gandey


May 4, 2007 — A startling 97% of cancer patients treated with cetuximab, matuzumab, or panitumumab have some degree of hypomagnesemia, a prospective clinical trial shows. The drugs targeting the epidermal growth factor receptor (EGFR) appear to compromise renal magnesium-retention capacity. "Our study is important because it shows that magnesium wasting will occur in all patients," lead author Sabine Tejpar, MD, from the University Hospital Gasthuisberg, in Leuven, Belgium, told reporters. "Previously, hypomagnesemia was thought to be restricted to an undefined subset of patients." She says predicting the risk for hypomagnesemia will also be important for patients receiving combination treatments with nephrotoxic and potential magnesium-wasting agents such as cisplatin.

The trial, published in the May issue of Lancet Oncology, found magnesium loss in all tested monoclonal antibodies targeting EGFR — suggesting a class effect. However, the researchers suggest, the incidence and severity might vary between products. They urge clinicians to carefully weigh all risks and benefits.

In an accompanying comment, Marwan Fakih, MD, from the Roswell Park Cancer Institute, in Buffalo, New York, writes, "To my knowledge, the Tejpar study is the first to show that some degree of hypomagnesemia occurs in almost all patients receiving EGFR-targeting monoclonal antibodies." Consistent with previous reports, he notes, clinically significant hypomagnesemia affected only a small group of patients receiving therapy.

Dr. Fakih writes that the study "elegantly" investigated magnesium wasting by measuring the slope of magnesium concentrations over time (starting from baseline) in 98 patients with metastatic colorectal cancer treated with monoclonal antibodies. Although the vast majority of patients experienced magnesium wasting during treatment, Dr. Fakih points out that significant interpatient variability in the serum magnesium concentration slopes was observed.

Monoclonal antibodies are becoming more popular in the management of patients with colorectal cancer. Based on favorable time-to-progression and response-rate outcomes from the Bowel Oncology with Cetuximab Antibody (BOND) study, the product is commonly used in the second- or third-line treatment of metastatic colorectal cancer.

Agents Targeting EGFR Gaining Popularity, but Adverse Effects Largely Unexplored

According to Dr. Fakih, the incorporation of cetuximab in the first-line treatment of metastatic colorectal cancer is becoming increasingly probable because of initial favorable time-to-progression results from a randomized study of fluorouracil, leucovorin, and irinotecan, with or without cetuximab. Hypomagnesemia is one of the commonly noted adverse events of this class of agents. Severe hypomagnesemia (grade 3 to 4) has been seen in 8 of 22 (36%) and 13 of 48 (27%) of patients who were treated with cetuximab. A review of 244 patients treated with cetuximab estimated a more conservative 10% to 15% incidence of severe hypomagnesemia.

Hypomagnesemia can cause dizziness, weakness, cardiac abnormalities, or even generalized convulsions. Agents targeting EGFR are being used increasingly to treat solid tumors in particular colorectal cancers. However, the extent of this effect in patients given these antibodies has not previously been fully assessed.

In the new study, Dr. Tejpar and colleagues say their finding explains why previous studies have underestimated the incidence of magnesium wasting. "They concentrate only on patients who are overtly hypomagnesemic — that is, the more severely affected patients who had time to develop hypomagnesemia during the relatively short treatment intervals," they note. The decrease of serum magnesium concentrations in patients who were treated with EGFR-inhibiting antibodies, with or without chemotherapy, was significantly different from those in patients who had received chemotherapy alone.

Chemotherapy has been associated with shifts in erythrocyte cellular-to-plasma-magnesium ratios. "However, in our series," they explain, "we can conclude that magnesium wasting is specifically due to EGFR inhibition. This finding is confirmed by the rapid normalization of serum magnesium concentrations on discontinuation of EGFR inhibition, while in most cases, patients went on to receive more chemotherapy."

The Challenge of Identifying and Treating High-Risk Patients

Age, baseline magnesium concentrations, and duration of treatment were considered risk factors for magnesium wasting. "This group of patients should be screened more vigorously with repeated measurements of magnesium concentrations during treatment," Dr. Fakih suggests.

Strategies for these high-risk populations include use of intermittent treatment with monoclonal antibodies to avoid the development of severe hypomagnesemia. "Such an intermittent treatment strategy has been shown to be successful for other agents that cause cumulative toxicities, such as oxaliplatin," Dr. Fakih explained. "At the Roswell Park Cancer Institute, we have implemented a cetuximab stop-and-go approach in patients with grade 3 and above hypomagnesemia needing more than 3-times-weekly infusions of intravenous magnesium replacement. Our experience confirms the complete resolution of hypomagnesemia within 2 months of stopping, and the feasibility of rechallenge with cetuximab when magnesium concentrations return to normal." In these patients, he notes, severe hypomagnesemia recurs rarely within 2 months from the start of cetuximab rechallenge.

Dr. Tejpar and colleagues are currently conducting a prospective randomized trial comparing low-dose and high-dose oral magnesium substitution in patients treated with cetuximab. "We expect diarrhea to remain a problem with all magnesium salt substitutions." They note that evidence exists in patients who have congenital-TRPM6 deficiencies that only high-dose oral substitution can stabilize concentrations of serum magnesium.

Lancet Oncol. 2007;8:366-367 , 387-394.