MIAMI BEACH, Fla.—About two-thirds of breast cancer patients who develop peripheral neuropathy after therapy with docetaxel recover after their chemotherapy regimen is completed, researchers reported here at the International Symposium on Supportive Care in Cancer.
However, about 10 percent of patients who never had peripheral neuropathy during six cycles of taxane-based therapy develop peripheral neuropathy one to three years after completing the regimen, said Lisa Eckhoff, MD, a fellow in oncology at Odense University Hospital in Denmark, speaking in an interview at her poster.
“About 15 percent of all the patients in our study reported peripheral neuropathy of grades 2 to 4 from one to 3.2 years after ending their treatment. Moreover, we found that persistent peripheral neuropathy has a significant negative impact on health-related quality of life.”
The researchers reviewed data from 1,725 patients who participated in a clinical trial that tested outcomes among early-stage breast cancer patients treated with two different lines of taxane-based chemotherapy:
* One group received three cycles of epirubicin at 90 mg/m2 plus cyclophosphamide at 600 mg/m2 followed by 100 mg/m2 of docetaxel for three cycles; and
* The second group received docetaxel at 75 mg/m2 plus cyclophosphamide at 600 mg/m2.
“Adjuvant chemotherapy with taxanes plays a key role in reducing the risk of recurrence and death from early-stage breast cancer but has side-effects such as peripheral neuropathy,” Eckhoff said.
One to three years after the trial was concluded, she and her colleagues contacted the women and asked them to complete a questionnaire aimed at determining short-term and long-term adverse events associated with treatment. The questionnaires were modeled after National Cancer Institute Common Terminology Criteria for Adverse Events and European Organisation for Research and Treatment of Cancer instruments. The researchers were able to analyze outcomes in 1,031 of the participants.
No peripheral neuropathy was observed among 790 of the patients (77%) 18 weeks after randomization. Of that group, no peripheral neuropathy was observed in 90 percent of the women one to 3.2 years after randomization, but 10 percent of the women who did not have peripheral neuropathy during the course of treatment later developed the condition.
“This late-onset peripheral neuropathy is difficult for the patients and frustrating for the clinician,” she said. “You cannot reduce the dose since the regimen is over, so there is no way to help them.”
Among the women who completed the study, 241(23%) reported they had early-onset peripheral neuropathy. After one to 3.2 years after randomization, 160 of these women were now free of the condition—about 66 percent of those initially experiencing the bothersome tingling, burning, pain, and numbness associated with peripheral neuropathy. The remaining 81 patients continued to feel the effects.
“This is good news,” she said. “We can tell patients who develop peripheral neuropathy during treatment that about two-thirds of them will have the condition resolve.”
The emergence of early peripheral neuropathy often has resulted in reducing the dose of taxanes delivered , Eckhoff noted. In the study, only about 65 percent of the women who developed peripheral neuropathy after the first cycle of chemotherapy received 100 percent of their prescribed treatment on time due to dose reductions.
“One of the issues in treatment in Denmark and elsewhere is whether to cut down on treatment due to peripheral neuropathy. The condition is different for different people. Maybe there is a different mechanism involved in people who had tingling or numbness or severe pain.
“We found that the risk of developing peripheral neuropathy was three-fold higher among women who were being treated with the higher dose of docetaxel.”
Suggestion that Frozen Gloves/Socks Are Helpful
Eckhoff said the analysis of the study appears to show that the use of frozen gloves or socks appeared to reduce the risk of developing peripheral neuropathy. “Patients who put on cold gloves and socks 15 minutes before receiving their hour-long infusion of docetaxel regimens were able to reduce their risk of peripheral neuropathy by 44 percent.
“Patients changed the gloves and socks a couple of times during the treatment to maintain the coolness, keeping the gloves and socks on until 15 minutes after the treatment. Even though the drugs are in the body longer than that period, it seems to help in preventing peripheral neuropathy.”
She cautioned, though, that such use is just an exploratory analysis: “The study was not designed to explore this question. We will examine it further in future studies.”
She noted that patients who are diabetic, who overuse alcohol, and who may be deficient in certain vitamins may also develop peripheral neuropathy. In this post-hoc analysis of peripheral neuropathy, though, none of those possibly causes were considered as variables. Eckhoff also noted that about three or four percent of people in the general population develop peripheral neuropathy of an unknown etiology —“So you have to keep that in mind, also,” she said.
The higher the grade of peripheral neuropathy experienced, the lower the score on quality-of-life surveys, she said. In the Global Health Status Quality of Life questionnaire, 874 women who had Grade 0 to 1 peripheral neuropathy scored an average of 76 on the scale; the 100 women who had self-reported Grade 2 peripheral neuropathy recorded an average score of 65; and women with Grade 3 to 4 peripheral neuropathy had an average score of 55.
Taxanes Appear to Affect Extremities More than Other Chemotherapies Do
Asked for her opinion for this article, Stephanie Bernik, MD, Chief of Surgical Oncology at Lenox Hill Hospital in New York City, said, “The toxicity of taxanes is often not well tolerated in patients undergoing chemotherapy for breast cancer. Taxanes appear to affect the extremities more than other chemotherapeutic agents. Taxanes can cause numbness and tingling of the fingers and toes, loosening or separation of the nail from the nail bed, hyperpigmentation and discoloration, and splinter hemorrhage.
“Studies are now suggesting that wearing cold gloves may reduce these side effects, by decreasing circulation to the extremities while the drugs are being infused. Decreased side effects theoretically will lead to better compliance with the difficult chemotherapeutic regimes that have been shown to be beneficial in the treatment of the disease.
“Larger, randomized trials are needed to see if indeed cold gloves lead to better adherence to drug schedules and dosing, and if this, in fact, leads to better outcomes,” she continued. “However, in the least, it appears that the cold gloves offer some relief to one of the most common and uncomfortable complications of taxane drugs.”
The symposium, which had the theme “Supportive Care Makes Excellent Cancer Care Possible,” is sponsored by the Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology. About 900 people from approximately 50 different countries attended this year.