Lani
08-10-2007, 11:11 AM
Minimize Chemotherapy-Induced Hand-Foot Syndrome
August 9, 2007 — Palmar-plantar erythrodysesthesia, also called hand-foot syndrome or hand-to-foot syndrome, is an uncomfortable and relatively frequent dermatologic toxic reaction to certain chemotherapeutic agents, and it remains poorly understood. Working to elucidate the problem, experts reporting in a review in the July issue of the Annals of Oncology discuss the challenges of managing this unfortunate adverse event.
"Palmar-plantar erythrodysesthesia typically presents with dysesthesia and tingling in the hands and feet, which usually appear 2 to 12 days after administration of chemotherapy," note the authors led by Domenica Lorusso, MD, from the department of oncology at Catholic University of the Sacred Heart, in Campobasso, Italy. "These symptoms may progress 3 to 4 days later into symmetrical edema and erythema of the palms and soles."
Erythematous plaques with violaceous and edematous patches in the palms, soles, and other high-pressure areas are usually mild and resolve in a week or 2. The problem may, however, evolve into blistering desquamation, crusting, ulceration, and epidermal necrosis if the next chemotherapy cycle is not delayed or the dose reduced. The reviewers point out that palmar-plantar erythrodysesthesia is often uncomfortable and can interfere with the ability to carry out normal activities.
Commenting on the review in an e-letter to the journal (Jaber R et al. Ann Oncol. 2007; published online April 11, 2007), Raja Jaber, MD, and colleagues from Stony Brook University Hospital, in New York, called the work "outstanding," and they report having read it with great interest. "As summarized by the Lorusso review, the only treatments so far are anecdotal and rely on topical agents with unclear benefits. Typically, the patients end up receiving a lowered dosage or have their treatments delayed." They emphasize that while dose reduction and schedule lengthening may decrease the incidence and ameliorate symptoms of hand-foot syndrome, there are no studies demonstrating that these altered schedules are equally effective in treating patients with metastatic breast cancer.
Dr. Lorusso and colleagues report the incidence of hand-foot syndrome is increased in patients receiving pegylated liposomal doxorubicin compared with conventional doxorubicin. The new drug is a long-circulating formulation in which doxorubicin hydrochloride is encapsulated within pegylated liposomes. It is approved to treat patients with metastatic breast cancer, advanced ovarian cancer, and acquired immunodeficiency syndrome–related Kaposi's sarcoma.
In studies that utilized the currently approved dose of pegylated liposomal doxorubicin of 50 mg/m2 every 4 weeks, the reviewers suggest that about 50% of patients receiving the product developed hand-foot syndrome and roughly 20% experienced grade 3 symptoms.
The researchers note that studies evaluating the development of hand-foot syndrome specifically associated with new-formulation doxorubicin have not fully identified the mechanism; however, data support the roles of drug excretion in sweat and local pressure as contributors.
Debilitating Complication of Cancer Therapy
"Palmar-plantar erythrodysesthesia is a debilitating complication of pegylated liposomal doxorubicin that can lead to delay, reduction, or discontinuation of chemotherapy," Dr. Jaber and colleagues write in their letter. "In addition, it will be an increasing problem due to a high incidence associated with new biologic multikinase inhibitors such as sorafenib and sunitinib."
The authors report on a case of liposomal doxorubicin–related persistent grade 3 hand-foot syndrome, refractory to the reported treatments, that responded dramatically to a short course of systemic treatment with oral prednisone.
"We propose oral prednisone as a safe treatment modality worth trying if palmar-plantar erythrodysesthesia occurs despite preventive dosages of dexamethasone, pyridoxine, and cooling of extremities," suggest the team from Stony Brook University Hospital. "Definite conclusions as to the efficacy of oral prednisone in the treatment of palmar-plantar erythrodysesthesia will require formal controlled clinical trials," they add.
In the meantime, Dr. Lorusso and colleagues emphasize the importance of patient education for early detection of hand-foot syndrome to minimize discomfort and complications. "At each visit, the patient should be carefully asked about signs and symptoms following the last dose," they explain.
Several pharmacologic and nonpharmacologic treatments have been used to prevent hand-foot syndrome. Nonpharmacologic interventions include avoiding undue pressure or rubbing of the skin and avoiding blood vessel dilation induced by hot showers or sun exposure.
In contrast, cooling is said to result in vasoconstriction, lessening circulation of drug to distal extremities. This in turn may lead to less drug extravasation into surrounding tissue, resulting in less toxicity. It is also possible that lower temperatures stabilize the liposomal configuration, thereby reducing the concentration of unencapsulated doxorubicin, the reviewers suggest.
Pharmacologic agents that have been evaluated for hand-foot syndrome include pyridoxine or vitamin B6, dexamethasone, amifostine, and COX-2 inhibitors. Topical agents are typically used to treat cases, and nonpharmacologic treatments that may relieve symptoms include emollients, aloe vera lotion, and moisturizing creams. Dr. Lorusso and colleagues name Bag Balm, a topical petroleum-lanolin-based ointment with the antiseptic ingredient hydroxyquinoline sulfate. They conclude, "Treatment measures must be started as soon as possible when necessary to help prevent progression of palmar-plantar erythrodysesthesia."
The researchers report having no significant financial relationships.
Ann Oncol. 2007;18:1159-1164. Abstract
August 9, 2007 — Palmar-plantar erythrodysesthesia, also called hand-foot syndrome or hand-to-foot syndrome, is an uncomfortable and relatively frequent dermatologic toxic reaction to certain chemotherapeutic agents, and it remains poorly understood. Working to elucidate the problem, experts reporting in a review in the July issue of the Annals of Oncology discuss the challenges of managing this unfortunate adverse event.
"Palmar-plantar erythrodysesthesia typically presents with dysesthesia and tingling in the hands and feet, which usually appear 2 to 12 days after administration of chemotherapy," note the authors led by Domenica Lorusso, MD, from the department of oncology at Catholic University of the Sacred Heart, in Campobasso, Italy. "These symptoms may progress 3 to 4 days later into symmetrical edema and erythema of the palms and soles."
Erythematous plaques with violaceous and edematous patches in the palms, soles, and other high-pressure areas are usually mild and resolve in a week or 2. The problem may, however, evolve into blistering desquamation, crusting, ulceration, and epidermal necrosis if the next chemotherapy cycle is not delayed or the dose reduced. The reviewers point out that palmar-plantar erythrodysesthesia is often uncomfortable and can interfere with the ability to carry out normal activities.
Commenting on the review in an e-letter to the journal (Jaber R et al. Ann Oncol. 2007; published online April 11, 2007), Raja Jaber, MD, and colleagues from Stony Brook University Hospital, in New York, called the work "outstanding," and they report having read it with great interest. "As summarized by the Lorusso review, the only treatments so far are anecdotal and rely on topical agents with unclear benefits. Typically, the patients end up receiving a lowered dosage or have their treatments delayed." They emphasize that while dose reduction and schedule lengthening may decrease the incidence and ameliorate symptoms of hand-foot syndrome, there are no studies demonstrating that these altered schedules are equally effective in treating patients with metastatic breast cancer.
Dr. Lorusso and colleagues report the incidence of hand-foot syndrome is increased in patients receiving pegylated liposomal doxorubicin compared with conventional doxorubicin. The new drug is a long-circulating formulation in which doxorubicin hydrochloride is encapsulated within pegylated liposomes. It is approved to treat patients with metastatic breast cancer, advanced ovarian cancer, and acquired immunodeficiency syndrome–related Kaposi's sarcoma.
In studies that utilized the currently approved dose of pegylated liposomal doxorubicin of 50 mg/m2 every 4 weeks, the reviewers suggest that about 50% of patients receiving the product developed hand-foot syndrome and roughly 20% experienced grade 3 symptoms.
The researchers note that studies evaluating the development of hand-foot syndrome specifically associated with new-formulation doxorubicin have not fully identified the mechanism; however, data support the roles of drug excretion in sweat and local pressure as contributors.
Debilitating Complication of Cancer Therapy
"Palmar-plantar erythrodysesthesia is a debilitating complication of pegylated liposomal doxorubicin that can lead to delay, reduction, or discontinuation of chemotherapy," Dr. Jaber and colleagues write in their letter. "In addition, it will be an increasing problem due to a high incidence associated with new biologic multikinase inhibitors such as sorafenib and sunitinib."
The authors report on a case of liposomal doxorubicin–related persistent grade 3 hand-foot syndrome, refractory to the reported treatments, that responded dramatically to a short course of systemic treatment with oral prednisone.
"We propose oral prednisone as a safe treatment modality worth trying if palmar-plantar erythrodysesthesia occurs despite preventive dosages of dexamethasone, pyridoxine, and cooling of extremities," suggest the team from Stony Brook University Hospital. "Definite conclusions as to the efficacy of oral prednisone in the treatment of palmar-plantar erythrodysesthesia will require formal controlled clinical trials," they add.
In the meantime, Dr. Lorusso and colleagues emphasize the importance of patient education for early detection of hand-foot syndrome to minimize discomfort and complications. "At each visit, the patient should be carefully asked about signs and symptoms following the last dose," they explain.
Several pharmacologic and nonpharmacologic treatments have been used to prevent hand-foot syndrome. Nonpharmacologic interventions include avoiding undue pressure or rubbing of the skin and avoiding blood vessel dilation induced by hot showers or sun exposure.
In contrast, cooling is said to result in vasoconstriction, lessening circulation of drug to distal extremities. This in turn may lead to less drug extravasation into surrounding tissue, resulting in less toxicity. It is also possible that lower temperatures stabilize the liposomal configuration, thereby reducing the concentration of unencapsulated doxorubicin, the reviewers suggest.
Pharmacologic agents that have been evaluated for hand-foot syndrome include pyridoxine or vitamin B6, dexamethasone, amifostine, and COX-2 inhibitors. Topical agents are typically used to treat cases, and nonpharmacologic treatments that may relieve symptoms include emollients, aloe vera lotion, and moisturizing creams. Dr. Lorusso and colleagues name Bag Balm, a topical petroleum-lanolin-based ointment with the antiseptic ingredient hydroxyquinoline sulfate. They conclude, "Treatment measures must be started as soon as possible when necessary to help prevent progression of palmar-plantar erythrodysesthesia."
The researchers report having no significant financial relationships.
Ann Oncol. 2007;18:1159-1164. Abstract