It may seem paradoxical to wear gloves to keep your hands cold, but a novel new therapy developed by French researchers does just that. As described in a study in the July 1 issue of the Journal of Clinical Oncology, the supportive-care therapy aims to prevent or reduce skin and nail damage from docetaxel chemotherapy by decreasing the amount of drug reaching the hands through increased cold.
It has been reported that nails become brittle or discolored in about 40% of patients receiving this taxane drug. Side effects are far more severe in about 3% of patients, with nails becoming infected and falling off (onycholysis). The researchers noted that hands are more frequently affected than feet.
Although some of these cases may be considered cosmetic, and none are directly life-threatening, the more serious problems may cause patients pain and discomfort that could lead to interruption or cessation of treatment.
In addition to its use for ovarian cancer, docetaxel has received recent FDA approvals either alone or in combination to treat a number of other cancers including breast, lung, and prostate; its safety and efficacy are also being assessed in current studies for head and neck and gastric cancers.
This increased patient use prompted Florian Scotté, MD, and colleagues at Georges Pompidou European Hospital in Paris to test whether wearing an experimental frozen glove would decrease damage to patients' nails or the skin on their hands.
During a 14-month period in 2002 to 2003, 45 patients (10 women, 35 men; median age 65) scheduled to receive docetaxel at 75 mg/m2 for various cancers were enrolled in the case-controlled Phase II study at three French hospitals.
None of the patients had received prior taxane treatments, or had nail or hand-skin problems. The final results included data on 45 patients for nail toxicity, and 41 of the patients for skin toxicity.
The patients wore a frozen glove—an Elasto-Gel flexible glove made by the French company Akromed—on their right hands only. The left hands served as the control.
Originally designed for rheumatism, the mitten-shaped hand coverings containing glycerin could be used at either hot temperatures (microwave) or cold (freezer).
The gloves were refrigerated at about −20ºF for three hours prior to use, with the patients wearing the glove for 90 minutes—15 minutes before and after a 60-minute infusion of docetaxel. After the first 45 minutes, patients received a new glove to sustain the cold temperature.
There were no nail problems in 89% of the gloved hands, compared with 49% of the uncovered left hands.
Onycholysis did not occur in any of the gloved hands, but affected 22% of the unprotected hands. Overall, skin problems occurred in 24% of the protected hands and in 53% of the control hands.
The appearance of nail toxicity was delayed in the gloved hands, but no difference was observed in the skin toxicity's median time to appearance.
Satisfaction with the treatment was expressed by 37 patients, with six patients dissatisfied, including five who left the study due to discomfort from cold intolerance.
In an interview conducted via e-mail, Dr. Scotté explained that the study was based on the use of cold caps to prevent hair loss from chemotherapy during the past 20 years.
“We imagined that vasoconstriction could have the same effect on nail bed or skin cells,” he said, adding that in France many oncology units use ice cubes during docetaxel treatments.
Following up on a case study of a breast cancer patient treated with docetaxel whose hand placed in contact with ice cubes showed no nail toxicity, while the other hand developed onycholysis, the researchers decided to use “a product like the cap, which seemed more efficient and elegant,” Dr. Scotté said.
He noted that it was a coincidence that the therapeutic glove manufacturer was also based in France, and that he and his colleagues are working with Elasto-Gel to develop other products, including a sock to evaluate protection against toxicity to the feet.
His team is now planning another study using other drugs with similar toxicity, and will also be testing the socks with docetaxel at 100 mg/m2.
Onycholysis Rare with Docetaxel
Another supportive care researcher not connected with the study, Maurie Markman, MD, Vice President of Clinical Research at the University of Texas M. D. Anderson Cancer Center, was asked for his opinion.
“It's a novel study and an interesting concept that needs confirmation in other trials, and needs to be more refined in terms of defining a population of patients who would stand to benefit,” he said in a telephone interview.
Dr. Markman, who is also Executive Vice President and Chief Academic Officer and Professor of Gynecologic Medical Oncology, expressed caution about applying the frozen glove therapy to all patients receiving docetaxel.
He said he had given docetaxel to many ovarian cancer patients over the years, using lower doses than the French study, and had never seen a case of onycholysis.
He said he was also concerned about how reducing the delivery of chemotherapy to certain areas might affect circulating tumor cells, and thought the therapy would perhaps be more appropriate in palliative settings when maximum dosage is not as important as in curative treatments.
He suggested that future studies may want to look at a population of patients who have already experienced a Grade 1 toxicity, and then randomize them to see if they received the glove or not, and assess patients who went on to have Grade 2 or 3 toxicity.
Dr. Markman said he also thought that the glove should be randomized between the right and left hands, and that a blinded observer should record data a month later.