Dealing With Taxotere® Side Effects
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by Richard Lam, MD

Prostate Oncology Specialists,

Marina del Rey, CA

Edited from PCRI Insights May, 2007 vol. 10, no.2

Overall, Taxotere® is well tolerated. However, successful administration of this powerful medicine requires diligent surveillance so that potential complications can be detected and corrected before they become severe.

Introduction

Taxotere® (docetaxel) is the most active chemotherapy for prostate cancer. In 2004, two randomized prospective studies1,2 comparing Taxotere and mitoxantrone, an older chemotherapy agent, clearly demonstrated that Taxotere was superior in three important criteria: overall survival duration, pain control, and quality of life. As a result, the FDA promptly approved Taxotere for the treatment of metastatic hormone refractory prostate cancer.

Taxotere in Early Disease

Besides its proven activity in metastatic disease, Taxotere is also being studied3 in the preventative, or adjuvant, setting. Effective treatment against advanced cancer works even better against earlier stages of the same type of cancer. Patients with high-grade prostate cancer may already harbor microscopic metastases. Intuitively, if one wants to improve the cure rate, one must also treat the microscopic disease outside the prostate. To date, the main adjuvant therapy for prostate cancer is hormone blockade.

The idea of using chemotherapy in earlier stage cancer is not unique or new. Adjuvant chemotherapy is a standard therapeutic approach in breast, colon, lung, bladder, pancreatic and stomach cancer. Adjuvant chemotherapy studies involving Taxotere are underway. We expect these studies will show that Taxotere can decrease relapse and improve survival in men with aggressive prostate cancer. Until the results of these studies are available, adjuvant Taxotere is a logical consideration, but cannot yet be considered a standard approach.

Methods of Administration

Taxotere is administered intravenously. There are two popular schedules: a higher dose administered every three weeks (q3wk) and a lower dose administered weekly (q1wk). The three-week dose appears to be more effective in the metastatic disease setting, but some patients are unable to tolerate the increased degree of tiredness that can occur with this regimen.

Fatigue affects about 50% of patients receiving Taxotere. Patients on the q3wk regimen usually report moderate to severe fatigue lasting about a week after each infusion. They usually recover to normal energy levels in time for the next treatment. Patients on the q1wk schedule usually experience a milder degree of fatigue, but of longer duration.

Before receiving Taxotere, tell your doctor if you notice swelling in the feet and legs or a slight weight gain; this may be the first warning sign of fluid retention. This means that your body is holding extra water. It is important that you take this medicine on schedule. Ref: www.taxotere.com

Managing Taxotere’s Effect on the Blood

Correcting anemia, defined as low red-blood-cell count, is the first step toward minimizing chemotherapy-related fatigue. Common causes of anemia include chemotherapy, hormone therapy, and cancer suppressing bone marrow function. Aranesp® and Procrit® are both synthetic versions of erythropoietin, a naturally occurring hormone that stimulates red blood cell production. These medications, when administered every two to three weeks during chemotherapy, can safely maintain adequate red-blood-cell production.

Besides monitoring for low red-blood-cell counts, one must also check the white-blood-cell count (WBC). We have found that a low WBC, called neutropenia, impairs the immune system and increases the risk of infection. Neutropenic infections have the potential to delay therapy, cause severe discomfort, induce unwanted hospitalizations and even cause death. Severe neutropenia is more likely with the q3wk schedule. Fortunately, this complication can be averted with judicious dosing of Taxotere and the use of white blood cell growth factors, such as Neupogen®, Neulasta®, and Leukine®.

Managing Taxotere’s Effects on the Alimentary Tract

Liver function also needs to be monitored via blood tests. Taxotere has been associated with irritation of the liver4. Fortunately, this side effect is reversible when the drug is stopped in a timely fashion or if the dosage is lowered. Sometimes, adding a supplement called milk thistle (silymarin) will correct the liver enzyme abnormality.

Maintaining adequate nutritional status is essential to a successful completion of chemotherapy treatment course. Taxotere can decrease the sense of taste, cause appetite loss, and occasionally induce nausea. Fortunately, severe nausea and vomiting is extremely rare. In order to prevent taste loss, we recommend sucking on an ice cube during chemotherapy infusion. The cold on the surface of the tongue shunts blood flow (and the Taxotere in the blood) away from the taste buds. Stimulants, such as Marinol and Megace are often helpful if appetite is a problem. The new generation antiemetic drugs, such as Zofran®, Anzemet® and Kytril®, are very effective solutions for nausea.

Another gastrointestinal complication of Taxotere is diarrhea. Usually, the severity is quite mild and can be controlled with over the counter or prescription medications. Occasionally, Taxotere will need to be stopped due to this complication.

Managing Other Side Effects

Taxotere can cause hair loss and skin side effects. The q3wk dose is associated with reversible hair loss in two-thirds of patients. The q1wk schedule is associated with milder hair loss about one-half of the time. The q1wk regimen usually results in more fingernail changes, which may include pain, brittleness, and fluid discharge. Cooling the fingernails with ice during infusion greatly reduces the risk of this complication.

Irritation of the tear ducts tends to occur more often with the q1wk regimen. This occurs when the tear ducts become scarred and are unable to drain tears adequately. Symptoms of this problem can include redness, chronic watery discharge, and dry eyes. To prevent this problem, we recommend the use of artificial tears to flush Taxotere from the eyes during and after each treatment.

Another side effect that can develop over time is a condition called neuropathy. Neuropathy is numbness and sometimes tingling in the toes and fingers. Generally, these symptoms are mild and slowly reverse after Taxotere is stopped. High doses of glutamine, an amino acid supplement, can minimize the severity of neuropathy.

Fluid retention can occur with Taxotere, especially with the q3wk regimen. The first signs of this complication are swelling of the feet and ankles and weight gain. If this fluid retention is in the chest or around the heart, it can be life threatening. Dexamethasone tablets may protect patients from significant fluid retention. Early use of diuretics can also prevent this problem.

Conclusion

Overall, Taxotere® is well tolerated. Prostate Oncology Specialists published a pilot trial5 in 2001 evaluating the tolerability of Taxotere in elderly men. The average age of the group was 78 years old. The oldest man was 87. Using the weekly protocol, we found that Taxotere could be tolerated by almost anyone. In that study, 17 out of 20 men completed a full course of therapy. The three men who decided to stop the treatment early did so because of excessive fatigue.

Taxotere has been proven to prolong survival in men with prostate cancer. Having another effective tool to fight this disease is much appreciated by the cancer community. However, successful administration of this powerful medicine requires diligent surveillance so that potential complications can be detected and corrected before they become severe.

References

1.) Tannock IF, deWit R, et al. Docetaxel plus prednisone or Mitoxantrone plus prednisone for advanced prostate cancer. N Eng Jo Med 2004;351:1502-1512.

2.) Petrylak DP, Tangen CM, Hussain MH, et al Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004 Oct 7; 351(15):1513-20.

3.) Taplin ME, Xie W, et al. Docetaxel, Estramustine, and 15-month Androgen deprivation for men with prostate-specific antigen progression after definitive local therapy for prostate cancer. J Clin Onc 2006; 24:5408-5413.

4.) Taxotere. Physicians Desk Reference 2007; 61:2932-2943.

5.) Scholz M, Strum S, et al. Low-dose weekly Docetaxel in elderly men with prostate cancer. Advances in Prostate Canc 2001; 5:7-9.

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