Neoplasms

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Breast Neoplasms

Syndrome

Hand-Foot Syndrome

Skin Diseases

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Capecitabine

Diclofenac

Carbamide Peroxide

Ethanol

Keratolytic Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

* Standard of care Urea-based cream (CARBAMIDE®) will be applied to hands and feet 2-3 times daily for 14 days starting from the first dose and cycle of Capecitabine (XELODA ®).
* Each Capecitabine (XELODA ®) cycle lasts for 21 days.
* Capecitabine (XELODA ®) dose :2g/m2 daily divided into 2 doses after breakfast and dinner for 14 days followed by 7 days Capecitabine free.
* Capecitabine (XELODA ®) dose will be modified according to treatment related side effects (26).
* This regimen will be repeated at each cycle of Capecitabine (XELODA ®) and lasts for 6 cycles (18 weeks) and preventive measures of Hand-foot syndrome will be applied (Avoid mechanical stress

* Standard of care Urea-based cream (CARBAMIDE®) will be applied to hands and feet twice daily for 14 days starting from the first dose and cycle of Capecitabine (XELODA ®).
* Each Capecitabine (XELODA ®) cycle lasts for 21 days.
* Capecitabine (XELODA ®) dose: 2g/m2 daily divided into 2 doses after breakfast and dinner for 14 days followed by 7 days Capecitabine free.
* Capecitabine (XELODA ®) dose will be modified according to treatment related side effects (26).
* This regimen will be repeated at each cycle of Capecitabine (XELODA ®) and lasts for 6 cycles (18 weeks) and preventive measures of Hand-foot syndrome will be applied (Avoid mechanical stress Plus
* Topical diclofenac (VOLTAREN®) Emulgel 1% 2-4g (2g = 4 fingertip Units (FTU)) twice daily 2 hours away from Urea-based cream (CARBAMIDE®) for 14 days starting from the first cycle and dose of Capecitabine.
* This regimen will be repeated at each cycle of Capecitabine (XELODA ®) and lasts for 6 cycles (18 weeks).

Urea is used to treat dry/rough skin conditions (such as eczema, psoriasis, corns, callus) and some nail problems (such as ingrown nails). It may also be used to help remove dead tissue in some wounds to help wound healing. Urea is known as a keratolytic. It increases moisture in the skin by softening/dissolving the horny substance (keratin) holding the top layer of skin cells together. This effect helps the dead skin cells fall off and helps the skin keep more water in.

(CARBAMIDE®)

(VOLTAREN®) Emulgel 1% contain the active ingredient diclofenac which belongs to the NSAIDS.it has analgesic and anti-inflammatory properties and due to its alcohol base it has a cooling effect.

(VOLTAREN®) Emulgel 1%

The aim of the study is to evaluate the efficacy of using combination of Urea-based cream (CARBAMIDE®) and topical diclofenac (VOLTAREN®) Emulgel 1% for improving the incidence of Hand-foot syndrome in histologically proven breast cancer Egyptian patients receiving single agent chemotherapy Capecitabine (XELODA ®) and Its effect on improving patients' quality of life.

Breast cancer (BC) is the most common cancer in women and the leading cause of death associated with cancer in females worldwide. BC, like most cancers, is a heterogeneous disease with a variety of molecular subtypes. Basal-like, Luminal-A, Luminal-B, HER2-positive/HER2-enriched/HER2-overexpressing BC, and normal-like tumors are the major subclasses identified by genetic profiling. Depending on the size, stage, grade, metastatic behavior, aggressiveness and intrinsic molecular subtyping of the tumor, age, menopausal status, overall health, comorbidities, and preferences of the patient, clinicians now have numerous options for breast cancer treatment. Treatment options include chemotherapy, hormone therapy, immunotherapy, radiotherapy, and surgery. The primary treatment option is usually surgery with the goal of complete resection of the major tumor mass. Surgery may be preceded by systemic neoadjuvant therapies to shrink the tumor in preparation for effective surgery and to maximize breast conservation.

The United States FDA has approved a number of drugs for breast cancer therapy, including Capecitabine (Xeloda). However, these drugs are very pricey and have numerous side effects. Patients frequently report decreased appetite, dehydration, diarrhea, Hand-foot syndrome (HFS), irregular periods, mouth and throat sores, nausea, and vomiting as side effects of Capecitabine. These side effects are difficult for patients who are already weakened by the disease to tolerate. Eventually these also affect the decision for further choice of treatment and impair the quality of life. This necessitates the development of novel drugs for the treatment of breast cancer and This is the role of drug repurposing.

The drug repositioning (aka drug repurposing, drug reprofiling, drug re-tasking, drug redesigning, drug resorting, drug reindication, indication switching, therapeutic switching) can be defined as exploring the new uses for an old clinically approved drug, with reduced risk, time and cost. Methotrexate, Raloxifene and Vinblastine are examples of Drug repurposing in breast cancer.

Hand-foot syndrome (HFS) also Known as palmoplantar erythrodysesthesia, is a common side effect of the fluoropyrimidine chemotherapy drug capecitabine. According to reports, 43 % to 71 %of patients receiving single-agent capecitabine chemotherapy have hand-foot syndrome of any grade.

It is characterized initially by palmoplantar numbness, tingling, or burning pain. These symptoms are usually accompanied by clearly defined erythema with or without edema, cracking, or desquamation. Blistering and ulceration may occur in the advanced stages. HFS may manifest as macular hyperpigmentation rather than erythema in people with darker skin (Fitzpatrick skin types V-VI). Symptoms can range from mildly to severely painful.

The pathogenesis of HFS is unclear, but it is assumed to be different for each drug class HFS causes a variety of toxic skin damage, ranging from non-specific scattered keratinocyte necrosis with basal vacuolar degeneration to full epidermal layer necrosis and (sub)epidermal blistering. In addition to eccrine squamous syringometaplasia, inflammation at the dermo-epidermal junction with papillary dermal edema, blood vessel dilation, and a lymphocytic infiltrate has been reported. The unique physiology of the palms and soles may clarify why the effects of these drugs are concentrated in these areas. The palms and soles are highly vascular, with higher rates of skin cell division than other skin areas, as well as high concentrations of eccrine glands and unique temperature modulation.

Unfortunately, no specific guidelines exist for HFS, and only a few randomized trials demonstrating the benefit of topical treatments are available. The most effective way to manage HFS once it has developed is to modify dose intensity in the form of a dose delay or dose reduction, which will affect patients' treatment outcomes and quality of life such as daily activities like walking or using of hands.

The treatment of choice for symptomatic HFS is determined by the severity of symptoms and their impact on Quality of Life (QoL). Vitamin E, steroids (oral dexamethasone), and analgesics are among the systemic treatment options. Current topical treatments are corticosteroids and emollients such as urea-based creams.

Capecitabine and its metabolites are thought to cause COX-2-mediated inflammation; COX-2 inhibition has been shown to be effective in the prevention of HFS. Topical non-steroidal anti-inflammatory inhibitors (NSAIDs), such as diclofenac, can inhibit COX-2 locally and may have a role in reducing HFS, without systemic side effects. However, no study has been conducted to date evaluating the role of topical COX inhibitors in reducing capecitabine-induced HFS. Hence, this study aimed to evaluate the efficacy and safety of topical diclofenac in reducing capecitabine-induced HFS.

The study consists of 2 Arms, A control arm which will only receive standard of care (CARBAMIDE) and an intervention arm which will receive (CARBAMIDE and VOLTAREN)

The Principle investigator and the Researcher are aware of the intervention taken for each participant. The participant will be blinded ( Single blinded)

Study is conducted on Breast Cancer patients which the majority are females and Males with Breast Cancer are considered rare

Effect of Topical Diclofenac on Clinical Outcome in Breast Cancer Patients Treated With Capecitabine

Effect of Topical Diclofenac on Clinical Outcome in Breast Cancer Patients Treated With Capecitabine: A Randomized Controlled Trial.

• Incidence of HFS between control arm (Urea-based cream (CARBAMIDE®)) and intervention arm (Combination of Urea-based cream (CARBAMIDE®) and (VOLTAREN®) Emulgel 1%) measured by (Common Terminology Criteria for Adverse Effects CTCAE v 5.0).

Cairo University

German University in Cairo

Micronutrients

Hematinics

Vitamins

Vitamin B 6

Pyridoxal

Pyridoxine

Vitamin B Complex

Trace Elements

Folic Acid

Vitamin B6

Folate

Vitamin B9

placebo

Thomas Lad, MD

Susan McDunn, MD

Capecitabine (Xeloda) a drug in cancer therapy. Its use is limited often by its toxicities. This study is asking if vitamin B6 can prevent one of the common toxicities of xeloda which is numbness and/or rash of the hands and feet, a condition called Hand and Foot syndrome. patients , starting capecitabine chemotherapy for their cancer, will participate in this study at John H. Stroger Jr. Hospital of Cook County. They will be randomized to receive either vitamin B6 or a placebo. investigators and patients will be blinded to the intervention.

Double-blind, placebo-controlled trial, with randomly assignment of eligible patients who were treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first 4 cycles of capecitabine treatment. The primary endpoint was the incidence and grade of Hand-Foot Syndrome (HFS) that occurred in both study arms.

Vitamin B6 Can Prevent Hand and Foot Syndrome in Cancer Patients Capecitabine Chemotherapy

A Randomized Trial to Determine if Vitamin B6 Can Prevent Hand and Foot Syndrome in Cancer Patients Treated With Capecitabine Chemotherapy

Incidence of HFS based on CTCTAE adverse event table

Grading of HFS: Grade 1, Grade 2, Grade 3 per NCI CTCTAE V 3

Cook County Health

Dir Clinical Research Office

Mineral

Copper

Copper Supplement

The patients will use a sock which contains copper fibers. The socks are sold in the free market (different Pharma stores) for various purposes such as prevention of diabetic foot. It is a product of Cupron company EPA :84542-2, 84542-3 from April 30 2009.

socks containing copper-oxide fibers

Rinat Yerusahlmi, MD

Aaron Sulkes, MD

Shtemmer Salomon, MD

Baruch Brenner, MD

Ofer Purim, MD

Victoria Neiman, MD

Noa Choraro, MD

Eyal Fenig, MD

Yulia Kundel, MD

Shulamith Rizel, MD

Luisa Bonila, MD

Rinat Yerushalmi, MD

Capecitabine is a common anti cancer drug. One of the most common side effects is a syndrome called hand and foot syndrome which comprises of hands and feet redness, swelling, dryness and painful sores. Quite often the drug dose is reduced to suboptimal level due to this side effect. There is no way to prevent or an effective way to treat this side effect. The investigators aim is to investigate whether wearing socks which contain copper fibers may prevent or alleviate the patient symptoms.

Capecitabine is a common anti cancer drug. One of the most common side effects is a syndrome called hand and foot syndrome which comprises of hands and feet redness, swelling, dryness and painful sores. Quite often the drug dose is reduced to suboptimal level due to this side effect. There is no way to prevent or an effective way to treat this side effect. Our aim is to investigate whether wearing socks which contain copper fibers may prevent or alleviate the patient symptoms.

The patients will use socks containing copper-oxide impregnated fibers which are sold in the Pharma stores without physician's prescription.(EPA numbers 8454-2, 8454-3 from April 30 2009).

Drug Toxicity and skin reaction will be documented.

Prevention of Capecitabine Induced Hand and Foot Syndrome

A Pilot Study- Prevention of Capecitabine Induced Hand and Foot Syndrome

within the first year from starting Capecitabine use

Rabin Medical Center

Medical Oncologist

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Celecoxib

Antimetabolites

Cyclooxygenase 2 Inhibitors

This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks) in addition to 200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle. The study duration will be the duration of the 6 cycles.

This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks).

200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle.

Celecoxib 200mg

Capecitabine-based chemotherapy

Ahmed Mohamed Kettana

Tarek Mohamed Mostafa, Professor of clinical pharmacy

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of malignancy-related mortality. Capecitabine has been approved for the treatment of colorectal cancer as first-line therapy. About 50%-68% of patients who take capecitabine develop Hand-foot syndrome. Hand-foot syndrome (HFS) is the most common adverse event of capecitabine-based chemotherapy. Initial symptoms of HFS are dysesthesia, tingling in the palms, fingers, and soles of the feet, and erythema, which may progress to an extremely painful and debilitating condition without prompt management. These symptoms can potentially lead to a worsened quality of life in patients taking capecitabine-based chemotherapy. Moreover, the adverse reaction necessitates dose-reduction or withdrawal of the chemotherapeutic agent. The mechanisms of HFS are still unknown, and there are limited data available on how to prevent them or manage them. However, different hypotheses of capecitabine-induced HFS pathogenesis have been suggested. One of the hypotheses stated that HFS is a kind of inflammation mediated by cyclooxygenase's (COX-2) over expression in palm and feet by capecitabine and its metabolites causing elevation of inflammatory markers as tumor necrosis factor alpha (TNF-α). COX-2 enzyme plays a main role in inflammation and pain. Therefore, celecoxib which is selective (COX-2) inhibitor may have a key role in the HFS treatment plan. A retrospective study and two prospective studies showed that combining capecitabine with celecoxib, a selective COX-2 inhibitor, can significantly reduce capecitabine-related HFS in colorectal cancer patients. Those studies were dependent on HFS grading only without measuring any markers. So, in our study we assess possible protective effect of celecoxib against capecitabine induced HFS and measure inflammatory marker as tumor necrosis factor alpha (TNF-α), oxidative stress marker as Malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) enzyme to show whether capecitabine induced HFS is caused by COX-2 mediated inflammation or not.

Possible Protective Effect of Celecoxib Against Capecitabine Induced Hand and Foot Syndrome in Patients With Colorectal Cancer

The change in hand and foot syndrome (HFS) grading according to common terminology criteria of adverse events (CTCAE) version 5.0.

Assessment of patients' quality of life using HFS-specific QOL questionnaire (HFS-14) based on patients' symptoms.

The change in serum levels of cyclooxygenase-2 (COX-2) enzyme.

The change in serum levels of tumor necrosis factor alpha (TNF-α) as a inflammatory marker.

The change in serum levels of malondialdehyde (MDA) as oxidative stress marker.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Topical Diclofenac on Clinical Outcome in Breast Cancer Patients Treated With Capecitabine	NCT05641246	Hand and Foot S...	(CARBAMIDE®) (VOLTAREN®) Emu...	18 Years - 80 Years	German University in Cairo
Vitamin B6 Can Prevent Hand and Foot Syndrome in Cancer Patients Capecitabine Chemotherapy	NCT00767689	Hand and Foot S...	Vitamin B 6 placebo	-	Cook County Health
Prevention of Capecitabine Induced Hand and Foot Syndrome	NCT01291628	Cancer	socks containin...	18 Years -	Rabin Medical Center
Possible Protective Effect of Celecoxib Against Capecitabine Induced Hand and Foot Syndrome in Patients With Colorectal Cancer	NCT05327751	Hand and Foot S... Erythrodysesthe... HFS Colorectal Canc...	Celecoxib 200mg Capecitabine-ba...	18 Years - 65 Years	Tanta University
Vitamin B6 Can Prevent Hand and Foot Syndrome in Cancer Patients Capecitabine Chemotherapy	NCT00767689	Hand and Foot S...	Vitamin B 6 placebo	-	Cook County Health

Spots Global Cancer Trial Database for hand and foot syndrome