Photobiomodulation in the treatment of palmar-plantar erythrodysesthesia: a randomised controlled clinical study protocol.

INTRODUCTION: Hand-foot syndrome, also known as palmar-plantar erythrodysesthesia (PPE), is a complication caused by chemotherapy. Clinically, it manifests as erythema and oedema on the palms of the hands and feet, dry and scaly skin, accompanied by a sensation of tightness and pain. Extreme cases have blisters and ulcerations that may require hospitalisation and/or pause in cancer treatment. It can also be accompanied by paraesthesia. Considering the characteristics, photobiomodulation (PBM) may reduce the PPE effects. The objective of this protocol will be to evaluate the efficacy of PBM in reducing PPE induced by capecitabine and 5-fluorouracil chemotherapy. METHODS AND ANALYSIS: This will be a randomised controlled, double-blind, double-centre clinical trial (Centro Asistencial del Sindicato Médico del Uruguay and Instituto Nacional del Cáncer from Uruguay). The sample population (40 individuals) will be divided into two groups: group 1 will receive moisturising cream plus PBM treatment and group 2 moisturising cream plus PBM sham treatment, at the ratio of 1:1. PBM will be performed at 630 nm two times per week in palmoplantar areas of the hands and feet (4 J/cm2), for 4 weeks. The PPE degree and the data referring to the chemotherapy treatment plan will be measured, prior to the start of treatment in the middle and at the end of it. Quality of life questionnaires will be applied at the beginning of the trial and at the end of treatment. The data will be analysed based on the intention-to-treat analysis and α<0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: The protocol was approved by the Research Ethics Committee of Universidad Católica del Uruguay (220316b), of Centro Asistencial del Sindicato Médico del Uruguay (221989) and of Instituto Nacional del Cáncer (2023-04). The recruitment has already started (March 2023). PROTOCOL VERSION: V.2, 27 October 2023. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05337423).

Dolutegravir-induced hand-foot skin reaction in a seropositive male: A rare presentation.

Hand-foot skin reaction (HFSR) is a specific but uncommon cutaneous side effect mainly following chemotherapeutic drugs such as multitargeted kinase inhibitors. HFSR is reversible and non-life-threatening. HFSR, also known as palmoplantar erythrodysesthesia, presents with various degrees of erythema, edema, hyperkeratosis, blister, and sometimes with a fine white scale. Dolutegravir, a first next-generation integrase inhibitor, is used with other antiretroviral therapy (ART) to treat mainly HIV infections. HFSR is diagnosed depending on the suggestive association of drug intake and characteristic palmoplantar eruption. ART can cause several cutaneous adverse drug reactions though no case report of dolutegravir-induced HFSR has been reported till date in literature. Here, we present a case of HFSR in a seropositive male on ART.

Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial.

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

Safety and efficacy study of oral metronomic capecitabine combined with pyrotinib in HER2-positive metastatic breast cancer: A phase II trial.

PURPOSE: To analyze the safety and efficacy of orally administered metronomic capecitabine plus pyrotinib in HER2 positive metastatic breast cancer (MBC) patients, we conducted a prospective phase II study with a single-arm design. METHODS: HER2 positive patients received oral metronomic capecitabine 500 mg three times a day and pyrotinib 400 mg per day. The primary endpoint was progression-free survival (PFS). Other endpoints included objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR) and safety. RESULTS: The study included 50 patients with MBC that was HER2-positive, while 1 patient was excluded due to nonstandard medication. The median PFS and OS was 11.9 months (95%CI 8.8-14.6) and 29.3 months (95%CI 24.4-34.8) respectively. ORR was 34.7%, and CBR was 81.6% with 2 CR (4.1%), 15 PR (30.6%) and 23 SD (46.9%). The mPFS in first- or second-line treatment was 12.2 months. The most frequent treatment-related adverse events included hand-foot syndrome, diarrhea, vomiting and nausea. Grade 3 adverse events occurred in 15(30.6%) patients, including hand-foot syndrome (12.2%), diarrhea (12.2%), vomiting (4.1%), and nausea (2.0%). 1 grade 4 adverse event of diarrhea (2.0%) was observed. CONCLUSION: The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2 positive metastatic breast cancer patients.

Paclitaxel-induced dorsal hand-foot syndrome.

Hand-foot syndrome (HFS), also known as palmoplantar erythrodysesthesia or acral erythema, is a known adverse effect of chemotherapeutic agents that most commonly presents as palmoplantar dysesthesia and erythematous plaques localized to the palms and soles. Paclitaxel is an uncommon cause of HFS and is notable for its unique presentation on the dorsal hands and feet. We present an unusual case of paclitaxel-induced HFS localized to the dorsal hands of a 66-year-old man with metastatic angiosarcoma. Early identification and management of HFS is critical to allow for continuation of chemotherapy while improving patient quality of life.

Fluoropyrimidine-induced hand-foot syndrome and cardiotoxicity: recommendations for the use of the oral fluoropyrimidine S-1 in metastatic colorectal cancer.

BACKGROUND: Fluoropyrimidines (FPs) are an essential part of the majority of systemic regimens in the treatment of metastatic colorectal cancer (CRC). The use of the oral FP S-1 has been approved by the European Medicines Agency as monotherapy or in combination with oxaliplatin or irinotecan, with or without bevacizumab, for the treatment of patients with metastatic CRC in whom it is not possible to continue treatment with another FP due to hand-foot syndrome (HFS) or cardiovascular toxicity (CVT). Subsequently, this indication has been included in the 2022 ESMO guidelines for metastatic CRC. Recommendations for use in daily practice are not available. PATIENTS AND METHODS: Based on peer-reviewed published data on the use of S-1 in Western patients with metastatic CRC who switched from infusional 5-fluorouracil (5-FU) or capecitabine to S-1 for reasons of HFS or CVT, recommendations for its use were formulated by an international group of medical oncologists with expertise in the treatment of metastatic CRC and a cardio-oncologist. RESULTS: In patients who experience pain and/or functional impairment due to HFS during treatment with capecitabine or infusional 5-FU, a switch to S-1 is recommended without prior dose reduction of capecitabine/5-FU. S-1 should preferably be initiated at full dose when HFS has decreased to grade ≤1. In patients with cardiac complaints, in whom an association with capecitabine or infusional 5-FU treatment cannot be excluded, capecitabine/5-FU should be discontinued and a switch to S-1 is recommended. CONCLUSIONS: These recommendations should guide clinicians in daily practice in the treatment of patients with metastatic CRC with FP-containing regimens.

Efficacy of regional cooling + oral dexamethasone for primary prevention of hand-foot syndrome associated with pegylated liposomal doxorubicin.

PURPOSE: Pegylated liposomal doxorubicin (PLD)-induced hand-foot syndrome (HFS) frequently lowers the quality of life of ovarian cancer patients. Wrist and ankle cooling, having a limited preventive effect, has been the commonest supportive HFS care. In this study, we retrospectively assessed the primary preventive effect of a combination of regional cooling and oral dexamethasone therapy (cooling + oral Dex) on HFS. METHODS: This study is a single-arm retrospective, observational study. Recurrent ovarian cancer patients were administered PLD ± bevacizumab. We retrospectively examined the efficacy of hands and feet cooling (from the start of PLD to the end) + oral Dex (day 1-5: 8 mg/day, day 6, 7: 4 mg/day) for primary HFS prevention. RESULTS: This study included 74 patients. The initial dose of PLD was 50 mg/m2 and 40 mg/m2 for 32 (43.2%) and 42 (56.8%) patients, respectively. HFS of Grade ≥ 2 and Grade ≥ 3 developed in five (6.8%) and one (1.4%) patient(s), respectively. The incidence of ≥ Grade 2 and ≥ Grade 3 HFS was much lower than those reported in previous studies. Dose reduction was required in 13 patients (17.6%) mainly because of neutropenia or mucositis; there was no HFS-induced dose reduction. Meanwhile, PLD therapy was discontinued mainly because of interstitial pneumonia (4 patients) and HFS (one patient). CONCLUSIONS: We demonstrated the efficacy of regional cooling and oral Dex for primary prevention of PLD-induced HFS. Although future prospective studies are needed to confirm its efficacy, this combination therapy can be considered for primary prevention of HFS in ovarian cancer patients on PLD.

Risk Factors of Capecitabine-Induced Hand-Foot Syndrome: A Single-Institution, Retrospective Study.

INTRODUCTION: This retrospective study was conducted to identify risk factors for developing hand-foot syndrome (HFS) and to determine new strategies for improving quality of life (QoL) in patients undergoing chemotherapy. METHODS: Between April 2014 and August 2018, we enrolled 165 cancer patients at our outpatient chemotherapy center who were undergoing capecitabine chemotherapy. Variables related to the development of HFS were extracted from the clinical records of patients for use in regression analysis. HFS severity was assessed at the time of completing capecitabine chemotherapy. The degree of HFS was classified in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Multivariate ordered logistic regression analysis was performed to identify risk factors for the development of HFS. RESULTS: Risk factors for the development of HFS included concomitant use of a renin-angiotensin system (RAS) inhibitor (odds ratio [OR] = 2.85, 95% confidence interval [CI] = 1.20-6.79; p = 0.018), body surface area (BSA) (high) (OR = 12.7, 95% CI = 2.29-70.94; p = 0.004), and albumin (low) (OR = 0.44, 95% CI = 0.20-0.96; p = 0.040). DISCUSSION/CONCLUSION: Concomitant use of RAS inhibitor, high BSA, and low albumin were identified as risk factors for the development of HFS. The identification of potential risk factors of HFS may assist in the development of strategies that can be used to improve QoL in patients receiving chemotherapy regimens that include capecitabine.

Capecitabine and Hand-foot Syndrome: A Case Report.

Capecitabine, a prodrug of 5-fluorouracil, is an FDA-approved drug for adjuvant treatment of colon, metastatic colorectal, and breast cancer. A variety of mucocutaneous adverse effects has been recognized with capecitabine. The pathogenesis of such manifestations still remains an enigma though various theories have been proposed. Here, we report two such cases. A 59-year-old female with carcinoma of the sigmoid colon on palliative therapy developed localized cutaneous hyperpigmentation of the palms and soles secondary to capecitabine in her 2nd cycle. Another case was of a 42-year-old female with stomach adenocarcinoma, who developed similar adverse effects after administration of capecitabine in her 4th cycle. Since these drugs have been widely used in recent years due to their relative ease in administration, the relative unawareness of Hand-foot syndrome (HFS) caused due to this drug makes it a prudent topic to be reported.

Pharmaceutical and clinical studies of celecoxib topical hydrogel for management of chemotherapy-induced hand-foot syndrome.

Hand-foot syndrome (HFS) can be categorized as a frequent dose-limiting side effect following administration of chemotherapeutic agents, which needs an effective medication to avoid dose reduction or discontinuation. Oral celecoxib has been proved to be the best pharmacological intervention to ameliorate the skin lesions. However, due to reported gastrointestinal and cardiovascular toxicity following its long-term administration, celecoxib topical application would be a safe alternative for skin disorders. In this work, first, we formulated and optimized a topical hydrogel of celecoxib (1%) and then we investigated its efficacy in the management of chemotherapy-induced HFS in cancer patients. Optimized hydrogel showed acceptable results for drug content, pH, rheology, and stability. Analyzing in vitro drug release study by various mathematical models, the optimized hydrogel showed a zero-order release pattern with 93.27 ± 1.56% cumulative celecoxib release within 8 h. Ex vivo permeation studies across Wistar rat skin indicated suitable skin retention of celecoxib for topical delivery. Twenty-nine patients suffering from HFS were randomized to receive celecoxib and the placebo hydrogels 2 times a day for 3 weeks. At the baseline and at the end of the trial, HFS grades were determined. No serious adverse events occurred in patients who completely followed the instructions. No statistically significant differences between two arms were observed at the baseline (p value = 0.38). By contrast, Wilcoxon signed-rank test showed significant differences when secondary grades (p value = 0.05) and grade differences (p values < 0.001) were analyzed. Overall, the study proved that celecoxib hydrogel could be a promising intervention to manage HFS side effect.

Capecitabine induces hand-foot syndrome through elevated thymidine phosphorylase-mediated locoregional toxicity and GSDME-driven pyroptosis that can be relieved by tipiracil.

BACKGROUND: Hand-foot syndrome (HFS) is a serious dose-limiting cutaneous toxicity of capecitabine-containing chemotherapy, leading to a deteriorated quality of life and negative impacts on chemotherapy treatment. The symptoms of HFS have been widely reported, but the precise molecular and cellular mechanisms remain unknown. The metabolic enzyme of capecitabine, thymidine phosphorylase (TP) may be related to HFS. Here, we investigated whether TP contributes to the HFS and the molecular basis of cellular toxicity of capecitabine. METHODS: TP-/- mice were generated to assess the relevance of TP and HFS. Cellular toxicity and signalling mechanisms were assessed by in vitro and in vivo experiments. RESULTS: TP-/- significantly reduced capecitabine-induced HFS, indicating that the activity of TP plays a critical role in the development of HFS. Further investigations into the cellular mechanisms revealed that the cytotoxicity of the active metabolite of capecitabine, 5-DFUR, was attributed to the cleavage of GSDME-mediated pyroptosis. Finally, we demonstrated that capecitabine-induced HFS could be reversed by local application of the TP inhibitor tipiracil. CONCLUSION: Our findings reveal that the presence of elevated TP expression in the palm and sole aggravates local cell cytotoxicity, further explaining the molecular basis underlying 5-DFUR-induced cellular toxicity and providing a promising approach to the therapeutic management of HFS.

Effect of Extra-Virgin Olive Oil on Hand Foot Syndrome and hs-CRP in Patients Receiving Capecitabine: A Randomized Trial.

BACKGROUND: Hand Foot Syndrome (HFS) is a frequent adverse effect observed in patients undergoing capecitabine chemotherapy, often leading to treatment disruptions and dose adjustments. Elevated C-Reactive Protein (hs-CRP) levels have been associated with the development of HFS. This study aimed to assess the potential of unrefined Extra Virgin Olive Oil (EVOO) supplementation in mitigating HFS and hs-CRP elevation among individuals receiving capecitabine chemotherapy. METHODS: Between November 2022 and May 2023, forty-five eligible participants were enrolled in this randomized trial. Patients with advanced colorectal or breast cancer were randomly allocated into three groups: an intervention group receiving unrefined EVOO supplementation (30 mL per day) alongside capecitabine, a placebo group receiving refined extra light olive oil (ELOO) supplementation (30 mL per day) alongside capecitabine, and a control group receiving capecitabine alone. The masking of both placebo and intervention groups was ensured through identical packaging and instructions, maintaining participant and physician blindness to the assigned treatments. Randomization, achieved via computer-generated sequences, ensured even distribution among the three groups. RESULTS: HFS incidences were notably lower in the EVOO group (13.3%) compared to the placebo (66.7%) and control (80%) groups. Instances of Grade 2 or more severe HFS were observed in 20% of placebo and 40% of control group patients. No cases of severe HFS were reported in the EVOO group. Moreover, EVOO supplementation led to a significant reduction in hs-CRP levels when contrasted with the placebo and control groups. These findings suggest that EVOO may serve as a preventive measure against HFS and exhibit anti-inflammatory effects in patients undergoing capecitabine chemotherapy. CONCLUSION: This study demonstrates the potential benefits of incorporating unrefined EVOO into the regimen of patients undergoing capecitabine chemotherapy. EVOO supplementation was associated with lower incidences of HFS and a reduction in hs-CRP levels, indicating its possible role in preventing HFS development and mitigating inflammation.

Pyridoxine Is Effective for Preventing Hand-Foot Syndrome Induced by Pegylated Liposomal Doxorubicin for Multiple Myeloma: The Results of a Randomized Study.

PURPOSE: Pegylated liposomal doxorubicin (PLD) is highly effective for treating multiple myeloma (MM). Hand-foot syndrome (HFS) is a dose-limiting adverse event of PLD that may reduce a patient's quality of life or prevent certain patients from receiving PLD. Several researchers have discovered that pyridoxine, an activated form of vitamin B6, may prevent PLD-associated HFS. We designed a prospective randomized trial to examine whether prophylactic pyridoxine might prevent the incidence or delay the occurrence of PLD-induced HFS in patients with MM. METHODS: Patients who met the trial's eligibility requirements were randomized and then administered either pyridoxine 100 mg twice daily or no pyridoxine, in both cases accompanied by their PLD-containing chemotherapeutic agent. Follow-up of patients was performed until the completion of induction therapy, the development of HFS or disease progression. RESULTS: Between January 1, 2017, and January 1, 2019, 105 patients were randomly assigned to the pyridoxine group (n = 52) or the no pyridoxine group (n = 53). In the pyridoxine and no pyridoxine groups, HFS developed after a median of 4 (range, 1-8 cycles) and 3 (range, 1-7 cycles) chemotherapeutic cycles, respectively. There were no grade 3 incidents recorded. Overall, 13.3% of patients experienced HFS. A 11 of 53 (20.8%) patients in the no pyridoxine group experienced HFS, compared to 3 of 52 (5.8%) patients in the pyridoxine group (P = .042); there was no difference in HFS grades (P = .725). CONCLUSIONS: The findings of benefit from prophylactic pyridoxine in this open-label trial have suggested its promise as a treatment for reducing HFS in MM patients. Further research with a placebo-controlled design is recommended. CLINICAL TRIAL REGISTRATION: ChiCTR2100050294.

Pharmacological prevention strategy for capecitabine-induced hand-foot syndrome: A network meta-analysis of randomized control trials.

Capecitabine-induced hand-foot syndrome (HFS) is common in clinical practice. There are many regimens used to prevent HFS. However, the most effective preventive regimen has not yet been identified. Thus, we conducted a network meta-analysis to investigate the best preventive regimen for HFS. The PRISMA-NMA guidelines were used in this study. The PubMed, Cochrane, and Embase databases were searched. The main endpoint was set as HFS of National Cancer Institute grade 2 or more. We included only randomized control trials. The P-score was used to rank the regimens. Among all the regimens, topical silymarin had the best preventive ability compared with the placebo (OR: 0.08; 95% CI: 0.01-0.71). The other identified effective regimen included pyridoxine (400 mg) and celecoxib; compared with the placebo, the odds ratio was 0.27 (95% CI: 0.08-0.91) and 0.41 (95% CI: 0.18-0.95), respectively. Topical silymarin is the most useful regimen for preventing capecitabine-induced HFS.

Oral hyperpigmentation as an initial clinical aspect of hand foot syndrome.

Hand-foot syndrome (HFS) is a common adverse effect of anticancer therapy. It is known to cause dermatological symptoms including acral erythema and dysesthesia of the palms and soles of the feet, swelling, pain, itching, and scaling. Some drugs, like capecitabine, are known to trigger this condition. However, pigmentation of the oral mucosa is a rare adverse effect. This study aims to report a case of oral mucosa hyperpigmentation caused by capecitabine therapy before the clinical diagnosis of HFS. A 58-year-old female, diagnosed with invasive breast duct carcinoma, had the central nervous system, liver, skin, and lung metastasis, using capecitabine every day for 14 cycles. Oral examination revealed multifocal black macules on the hard palate, bilateral buccal mucosa, gingival mucosa, and dorsum of the tongue. The clinical hypothesis was oral mucosa hyperpigmentation by capecitabine use and only periodic follow-up was necessary. Hyperpigmentation of oral mucosa by capecitabine is a rare consequence of neoplastic therapy and your association with HFS is unclear, and poorly reported. The report of these events is important to alert oncology health teams about the individual tolerance to capecitabine therapy.

Hand-foot syndrome induced by chemotherapy drug: Case series study and literature review.

INTRODUCTION: Chemotherapy drugs can be responsible of several side effects such as hand-foot syndrome (HFS). This syndrome is also called "palmar-plantar erythrodysesthesia" and "acral erythema." Without proper management, it can deteriorate the quality of life of a patient, leading to temporary or definitive stop of chemotherapy. AIM OF THIS STUDY: To identify the epidemiological and clinical characteristics of patients, the risk factors for occurrence and worsening of this syndrome, and the drugs most likely to be responsible of HFS. METHODS: Our study was retrospective, including 42 patients with HFS secondary to a chemotherapy drug. These cases were notified to the National Center of Pharmacovigilance over 7 years. The severity of HFS has been classified according to the NCI-CTCAE v4.0 classification. RESULTS: Our population was composed of 40 women and 2 men. The mean age was 51 years. Docetaxel was the main drug associated with this adverse effect. Hands were involved in all cases and were sometimes associated with other skin surfaces apart from feet. Erythema of the hands and/or feet was present in all patients; it was associated with edema in more than half of the cases. The distribution of different grades according to the NCI-CTCAE classification among the patients was almost equal: 28% Grade 1, 36% Grade 2, and 36% Grade 3. HFS occurred mainly after the first course of chemotherapy with a mean period of 3-4 days. The regression of HFS occurred more rapidly for Grade 1 and Grade 2 compared with Grade 3, especially when assisted by symptomatic treatment. The recurrence rate of HFS for those patients with decreased doses, spacing of cures, and/or symptomatic and prophylaxis treatment was 25%. CONCLUSION: An early detection of HFS, associated with preventive measures, enables patients to continue the chemotherapy.

Study protocol of a single-arm phase 2 study evaluating the preventive effect of topical hydrocortisone for capecitabine-induced hand-foot syndrome in colorectal cancer patients receiving adjuvant chemotherapy with capecitabine plus oxaliplatin (T-CRACC study).

BACKGROUNDS: Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. METHODS: This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. DISCUSSION: This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.

Prophylactic strategies for hand-foot syndrome/skin reaction associated with systemic cancer treatment: a meta-analysis of randomized controlled trials.

PURPOSE: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are common toxicities of several systemic cancer treatments. Multikinase inhibitor-induced HFSR is distinguished from chemotherapy-induced HFS in terms of pathogenesis, symptomatology, and treatment. Multiple trials have investigated the efficacy of preventive strategies such as COX-inhibitors, pyridoxine, and urea cream; however, no consensus has been made. This meta-analysis evaluated data from high-quality trials to provide strong evidence in forming recommendations to prevent systemic cancer therapy-induced HFS/HFSR. METHODS: A systematic search of PubMed, Embase, Cochrane, clinical trials databases, and hand searching were utilized to identify randomized trials (RCTs) investigating prophylactic strategies for HFS/HFSR in cancer patients receiving systemic treatment. Trials published until August 2021 were included. Using the random effects model, pooled odds ratios were calculated for rates of all-grade and severe HFS/HFSR. Subgroup analysis based on type of cancer treatment given was done. RESULTS: Sixteen RCTs were included (N=2814). For all-grade HFS/HFSR, celecoxib (OR 0.52, 95% CI 0.32-0.85, p=0.009) and urea cream (OR 0.48, 95% CI 0.39-0.60, p<0.00001) both showed statistically significant risk reduction. Celecoxib was effective in preventing HFS in patients who received capecitabine (50.5% vs 65%, p=0.05), while urea cream was effective in both capecitabine HFS (22.3% vs 39.5%, p=0.02) and sorafenib-induced HFSR (54.9% vs 71.4%, p<0.00001). Pyridoxine at higher doses showed a trend towards benefit in preventing all grade HFS (69.6% vs 74.1%, p=0.23). CONCLUSIONS: Urea cream and celecoxib are both effective in preventing HFS/HFSR in patients receiving systemic cancer treatment. Particularly, celecoxib is more effective in preventing all-grade capecitabine-induced HFS, while urea cream shows more benefit in preventing moderate to severe sorafenib-induced HFSR. Studies investigating optimal dosing for celecoxib and urea cream are recommended. There is inadequate evidence to make recommendations regarding pyridoxine.

Milk and Egg Are Risk Factors for Adverse Effects of Capecitabine-Based Chemotherapy in Chinese Colorectal Cancer Patients.

BACKGROUND: Chemotherapy-induced adverse effects (CIAEs) remain a challenging problem due to their high incidences and negative impacts on treatment in Chinese colorectal cancer (CRC) patients. We aimed to identify risk factors and predictive markers for CIAEs using food/nutrition data in CRC patients receiving post-operative capecitabine-based chemotherapy. METHODS: Food/nutrition data from 130 Chinese CRC patients were analyzed. Univariate and multivariate analyses were used to identify CIAE-related food/nutrition factors. Prediction models were constructed based on the combination of these factors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination ability of models. RESULTS: A total of 20 food/nutrition factors associated with CIAEs were identified in the univariate analysis after adjustments for total energy and potential confounding factors. Based on multivariate analysis, we found that, among these factors, dessert, eggs, poultry, and milk were associated with several CIAEs. Most importantly, poultry was an overall protective factor; milk and egg were risk factors for hand-foot syndrome (HFS) and bone marrow suppression (BMS), respectively. Developed multivariate models in predicting grade 1 to 3 CIAEs and grade 2/3 CIAEs both had good discrimination (AUROC values from 0.671 to 0.778, 0.750 to 0.946 respectively), which had potential clinical application value in the early prediction of CIAEs, especially for more severe CIAEs. CONCLUSIONS: Our findings suggest that patients with high milk and egg intakes should be clinically instructed to control their corresponding dietary intake to reduce the likelihood of developing HFS and BMS during capecitabine-based chemotherapy, respectively. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03030508.