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BACKGROUND Pegylated liposomal doxorubicin (PLD) uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands, producing toxic free radicals and oxidative damage, resulting in hand-foot syndrome (HFS). Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands; thus, decreasing the incidence and severity of HFS. AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term. METHODS This is a retrospective cohort study. Female breast cancer patients (n = 101) who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group (51 patients) and the control group (50 patients). Patients in the control group only received routine care, while the patients in the cooling group applied cooling patches, based on routine care, to the palm and back of the hands 15 min before chemotherapy infusion for 10 h. All patients took a corresponding dose of dexamethasone orally one day before chemotherapy, on the day of chemotherapy, and one day after chemotherapy. SPSS23.0 version was used to analyze the data in this study. The occurrence and severity of HFS was analyzed by the Mann-Whitney U test, and scores were analyzed by the Student’s t test or Wilcoxon rank-sum test. A P value < 0.05 was regarded as statistically significant. RESULTS In this study, neither group of patients developed Grade 3 HFS. In the control group, the incidence of Grade 1 HFS and Grade 2 HFS was 38% and 2%, respectively. However, in the cooling group, only one person developed Grade 1 HFS (2%), and none of the patients developed Grade 2 HFS. These findings showed that cooling patches can effectively reduce the frequency and severity of HFS (P < 0.0001) in the short-term. Before the fourth chemotherapy cycle, although general self-efficacy scale scores in the cooling group were low, they were still significantly higher than those in the control group (17.22 ± 5.16 vs 19.63 ± 6.42, P = 0.041). Compared with the control group, the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower (18.08 ± 7.01 vs 14.20 ± 7.39, P = 0.008). CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term. In addition, it may help delay the decline in patients’ self-efficacy.

SummaryBackground. Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC. Methods. This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results. A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment. Conclusion. The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.

Background:Hand-foot syndrome (HFS), also known as palmoplantar erythrodysesthesia, is a common adverse effect of the fluoropyrimidine chemotherapy agent capecitabine. Hand-foot syndrome of any grade is reported to affect 43% to 71% of patients treated with single-agent capecitabine chemotherapy. Although not life-threatening, it can have adverse effects on the quality of life (QoL) and daily living activities of a patient. Sometimes the dose interruptions and reductions required after observation of HFS can also impact on dose intensity and treatment outcomes. As an option for the treatment of this case, we would reported our preliminary study of the effectiveness of moist exposed burn ointment (MEBO) for stage II and III HFS. Methods: We will evaluate the clinical sign and symptoms of hand foot syndrome grade II and III associated with capecitabine as adjuvant chemotherapy agent on advanced stage colorectal cancer. All patients with HFS will treated with topical MEBO twice daily, the clinical improvement of the symptoms will be recorded. Results: We reported 8 cases of grade II and III hand foot syndrome, 2 patients were grade III HFS and the others were grade II. These symptoms occurred after 2 until 3 months after capecitabine administration for locally advanced (stage III) colonic adenocarsinoma. Topical MEBO were used twice a day for 3 months, pain reduction was achieved with no capicetabine dose interruption and reduction during chemotherapy period. Allergic reaction was not found during and after MEBO application in this case. Conclusion:Moist exposed burn ointment was an effective treatment option in managing hand foot syndrome, better option in reducing the pain without interrupting the capecitabine doses.

Objectives: Hand-foot syndrome (HFS) is a common adverse effect of chemotherapy in cancer patients. This review synthesizes research results to assess the effect of traditional Korean medicine (TKM) on HFS in cancer patients.Methods: Four databases (PubMed, The Cochrane Central Register of Controlled Trials, Research Information Sharing Service, China National Knowledge Infrastructure) were searched for randomized controlled trials (RCTs) to assess the effects of TKM on HFS. The effects and quality of RCTs were assessed with the Cochrane risk of bias (ROB) tool.Results: Six RCTs met our study criteria. In all six, TKM showed improvement in HFS symptoms as well as quality of life scores when compared to the control group. However, the methodological quality of RCTs was relatively low due to the unclear or high ROB.Conclusions: TKM would be helpful to patients with HFS after chemotherapy. To clarify the clinical efficacy of TKM, well-designed studies are required in the future.

Purpose Hand-foot syndrome (HFS) is a frequent dose-limiting adverse reaction of fluoropyrimidine drugs like capecitabine and 5-flourouracil (5-FU) in breast and gastrointestinal cancers. It has been shown that conventional application of Lawsonia inermis L. (Henna) is effective in ameliorating of the skin lesions. To increase the patient compliance, in this study we formulated a standardized topical hydrogel (H.gel) containing the hydroalcoholic extract (10%) of Henna and evaluated its clinical efficacy for the management of fluorouracil associated HFS. Material and methods The topical dosage form was standardized based on its Lawsone content. Eighteen patients suffering from HFS were randomized to receive H.gel and the placebo four times a day for 2 weeks. At the baseline and at the end of the trial, HFS grades were determined. Results and conclusions Allergic reactions following administration of H.gel were observed in one patient, while no serious adverse events occurred in the others. No statistically significant differences between two arms were observed at the baseline (p-value = 0.133), after treatment (p-value = 0.590) and grade differences (p-value = 0.193). The applied hydrogel showed less efficacy compared to the traditional method of using Henna, meaning that Lawsone may not be a good indicator for standardizing the topical dosage form.

BACKGROUND Capecitabine is used in combination with lapatinib as palliative treatment for human epidermal growth factor receptor 2 - positive metastatic breast cancer. The most frequently reported adverse events attributed to capecitabine include diarrhea, hyperbilirubinemia, and hand-foot syndrome (HFS). A number of cutaneous adverse events have been attributed to capecitabine, including Stevens-Johnson syndrome (SJS) as a rare and potentially life-threatening mucocutaneous condition. We report the first case involving concurrent SJS and HFS after capecitabine and lapatinib treatment. CASE SUMMARY A 70-year-old woman with a history of breast cancer treatment visited our hospital for evaluation of painful skin lesions. Six weeks earlier, she had been prescribed capecitabine plus lapatinib as treatment for metastatic breast cancer. She subsequently developed worsening erythema and bullae on her palms and soles, as well as reddish macules on her back and chest wall. Histopathological evaluation of the chest wall lesions revealed extensive eosinophilic epidermal necrosis and separation of the epidermis from the dermis. The capecitabine plus lapatinib treatment was discontinued immediately and treatment was started using systemic steroids. This treatment resolved most lesions, although the lesions on her palms and soles required Vaseline gauze dressings, which resulted in re-epithelialization. Therefore, we determined that the patient had concurrent SJS and HFS. Although the dermatological problems resolved, the patient ultimately died because of multiple organ failure. CONCLUSION Oral capecitabine treatment carries a risk of both HFS and also life-threatening adverse cutaneous drug reactions, such as SJS.

Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a localized cutaneous adverse event (CAE) associated with a variety of chemotherapeutic agents, such as doxorubicin, fluorouracil, cytarabine, and docetaxel. HFS is characterized by painful erythema, edema, and desquamation of the skin, most prominently involving the hands and soles of the feet. However, HFS primarily affecting the dorsal hands and feet (also called periarticular thenar erythema and onycholysis or PATEO) is known to occur as a class-based effect with the taxane chemotherapeutic drug class. A 58-year-old African American female with breast cancer began to develop a pruritic bilateral dorsal hand eruption four weeks into a weekly regimen of paclitaxel. On exam, desquamative erythematous and violaceous plaques on the dorsal hands were noted, which were debilitatingly painful and necessitated treatment interruption. Histopathologic sections showed a focal interface dermatitis with keratinocyte apoptosis, dyskeratosis, and atypical mitoses with abnormal maturation. Clinicopathologic correlation strongly supported a diagnosis of taxane-induced HFS. Increased awareness of this HFS variant that preferentially affects dorsal acral sites may improve early identification and/or prevention of this cutaneous adverse reaction. This article is protected by copyright. All rights reserved.

Objective The objective of this article was to offer practical operational process for pharmacists to successfully conduct integrated pharmaceutical care for patients with hand-foot syndrome associated with chemotherapeutic agents and targeted drugs which may facilitate the work of first-line clinical pharmacist. Data sources: A literature review was conducted in March 2020 of Pubmed, Medline, and EMBASE (2010-2020) using terms such as: hand-foot syndrome, hand-foot skin reaction, palmar-plantar erythrodysesthesia, chemotherapeutic agent, and multikinase inhibitor. Appropriate references from selected articles were also used. Data summary: This paper involves 81 articles including review articles, meta-analysis, and clinical trials which focused on every aspect of hand-foot syndrome, such as manifestation, mechanism, occurrence rate, onset time, patient education, self-monitor scale, and management. Studies were thematically divided into four parts (clinical presentation of HFS, risk stratification, initiation of pharmaceutic care, and management of the adverse reaction). Conclusion HFS is one of the common adverse events which was associated with many chemotherapeutic agents and multikinase inhibitor drugs. Although the mechanisms and histopathology may be different, they due share some common clinical manifestations. As part of integrated pharmaceutical care for cancer patients, it is important to conduct patient education about the risk of hand-foot syndrome and basic knowledge about hand-foot syndrome management before initiating anticancer therapy. Once hand-foot syndrome happens, evidence-based management could try. If the hand-foot syndrome is intolerable, dose reduction or discontinuation of the anticancer therapy should be considered.

Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a major side effect of capecitabine. Although the pathogenesis of HFS remains unknown, some studies suggested a potential involvement of inflammation in its pathogenesis. Proton pump inhibitors (PPIs) have been reported to have anti-inflammatory effects. In this study, we investigated the ameliorative effects of omeprazole, a PPI on capecitabine-related HFS in mice model, and a real-world database. Repeated administration of capecitabine (200 mg/kg, p.o., five times a week for 3 weeks) increased fluid content, redness, and tumor necrosis factor (TNF)-α substance of the mice hind paw. Co-administration of omeprazole (20 mg/kg, p.o., at the same schedule) significantly inhibited these changes induced by capecitabine. Moreover, based on the clinical database analysis of the Food and Drug Administration Adverse Event Reporting System, the group that has used any PPIs had a lower reporting rate of capecitabine-related PPE than the group that has not used any PPIs. (6.25% vs. 8.31%, p

Background Hand-foot skin reaction (HFSR) is the most common regorafenib-induced adverse event and is in need of effective prevention and palliation. Materials and Methods The Regorafenib Dose Optimization Study (ReDOS), a four-arm, previously published trial with a 1:1:1:1 randomization scheme, was analyzed in a manner in keeping with the original protocol to assess whether clobetasol 0.05% cream (a corticosteroid) applied to the palms and soles twice per day for 8 weeks was more effective when prescribed preemptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the first two cycles of regorafenib. Results Sixty-one patients received preemptive clobetasol, and 55 received reactive clobetasol. Groups were balanced on demographics. Over the first two cycles, no evidence of HFSR occurred in 30% with preemptive clobetasol versus 13% with reactive clobetasol (p = .03). During the first cycle, 54% and 45% of patients had no HFSR with preemptive and reactive clobetasol, respectively (p = .35). During the second cycle, 33% and 15% had no HFSR with preemptive and reactive clobetasol, respectively (p = .02). During the second cycle, rates of grade 1, 2, and 3 HFSR were 30%, 8%, and 3%, respectively, with preemptive clobetasol and 43%, 18%, and 7%, respectively, with reactive clobetasol (p = .12). Patient-reported outcomes showed HFSR compromised nearly all activities of daily living with worse quality of life in patients who received reactive versus preemptive clobetasol. No clobetasol-induced adverse events were reported. Conclusion Preemptive clobetasol might lessen regorafenib-induced hand-foot reactions compared with reactive therapy. Further confirmatory studies are needed in a larger patient cohort. Implications for Practice Regorafenib causes hand-foot skin reactions. Preemptive clobetasol, a high-potency topical corticosteroid, appears to lessen the severity of this adverse event. Although further study is needed, the favorable adverse event profile of this intervention might prompt clinicians to discuss this option with their patients.

Background This study sought to test the effectiveness of EVOSKIN®Palm and sole moisturizing cream (PSMC) in preventing and treating hand-foot syndrome (HFS) during capecitabine chemotherapy. Methods Stage II/III colorectal cancer patients receiving capecitabine adjuvant chemotherapy were randomly allocated to receive either EVOSKINPSMC or physiological saline treatments for their hands and feet. Treatment was initiated along with adjuvant chemotherapy and continued till the end of chemotherapy. Participants' skin responses were evaluated every 3 weeks. Results During the study, 51 participants in the EVOSKIN PSMC group and 54 participants in the physiological saline group completed at least three cycles of capecitabine chemotherapy. The total incidence of HFS in the EVOSKIN PSMC group was lower than that in the physiological saline group (56.8% vs. 75.9%, P=0.006), as was the incidence of Grade 3/4 HFS (6.0% vs. 18.5%, P=0.011). The incidence of HFS became significant after 6weeks of chemotherapy. Further, the incidence of severe HFS was significant from as early as 3weeks after the commencement of chemotherapy despite the use of EVOSKIN PSMC to manage the condition. Notably, the incidence of Grade 1/2 HFS was not statistically significant between the two groups (26/51 vs. 32/54, 52.0% vs. 59.2%, P=0.194). Conclusions The incidence of severe HFS among individuals using oral capecitabine can be reduced by the prophylactic treatment of EVOSKIN PSMC, this treatment is reasonable and acceptable for patients with capecitabine chemotherapy.

Background: we speculate that low level laser might decrease the inflammatory reactions and pain associated with hand foot syndrome because low-level laser therapy, has proven high efficacy in the management of chemotherapy/radiation-induced oral mucositis and radiation-induced dermatitis that might share some physio- pathological characteristics with hand foot syndrome, Objective: To determine whether low-level laser therapy (LLLT) might be effective for chemotherapy-induced hand foot syndrome (HFS). Patients and methods: This study included thirty patients with hand foot syndrome (grade I -II - III according to WHO definition) after treatment with chemotherapy from both sexes. Their ages ranged from 35-60 years. Patients were randomly assigned into two equal groups in number. Group A (the study group) included fifteen patients received low-level laser therapy in addition to the traditional medical treatment. Group B (control group) included fifteen patients received the traditional medical treatment. The participants of both groups were assessed by the following tools to assess the impact of HFS on quality of life by visual analogue scale and HFS-14 questionnaire. Results: There was a significant decrease in VAS and HFS-14 questionnaire score post treatment in the study and control groups compared to that of pretreatment (p > 0.001). The percentages of decrease in VAS and HFS-14 questionnaire score in the study group were 48.29% and 34.22% respectively, while for the control group, they were 28.75% and 18.82% respectively. Conclusion: Based on this study, it could be concluded that LLLT might represent a useful approach for the management of HFS.

There is no drug therapy without risk for toxicity. The patient must tolerate some toxic or idiosyncratic adverse events (e. g. hand foot syndrome). After life threatening adverse effects, one needs to screen (hyperkalemia). The sick-day-rule should be communicated with the informed patient as for example stopping SGLT2-inhibitors (loss of appetite, hypotension). The list of prescriptions should regularly criticized for dangerous or superfluous medicines (deprescribing).

Purpose Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients.Materials and Methods Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model.Results We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression.Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

Background Hand-foot syndrome (HFS) is a common systemic skin toxicity syndrome caused by chemotherapy agents. However, there is no uniform clinical treatment for HFS. It is reported that pyridoxine (vitamin B6) can be used to prevent HFS, but the evidence is insufficient. Aim To determine whether pyridoxine can be used to prevent HFS caused by chemotherapy agents. Methods Literature database searches were performed on PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure. The efficacy of pyridoxine was evaluated by the incidence of HFS (any grade) or severe HFS (grade ≥ 2). Results Fourteen studies involving 1570 patients were included in this meta-analysis. There were no significant differences between the pyridoxine and control groups in the prevention of HFS (OR = 0.84, 95% CI 0.67-1.05, P = 0.09) or in the incidence of grade ≥ 2 HFS (OR = 0.87, 95% CI 0.70-1.09, P = 0.39, respectively). The subgroup analysis of pyridoxine dose also showed no significant difference between the two groups in preventing HFS grade ≥ 2 (OR = 0.79, 95% CI 0.62-0.99, P = 0.30). Conclusions We did not find adequate evidence to support the idea that the use of pyridoxine can prevent HFS and reduce the incidence of HFS grade ≥ 2. However, the preventive use of pyridoxine might have a tendency to reduce the incidence of HFS.

Background: Hand-foot skin reaction (HFSR) is the most common adverse event during sorafenib treatment, which is the main reason for dose de-escalation or discontinuation of sorafenib in hepatocellular carcinoma (HCC) patients. Here, we aimed to investigate the role of urea cream in the prevention or amelioration of HFSR severity. Methods: HCC patients at 13 hospitals in Korea were recruited from May 2016 to May 2018. Patients were treated with placebo cream and urea cream for 12 weeks concomitantly with sorafenib treatment. Development of HFSR, score for Hand-Foot Skin Reaction and Quality of Life (HF-QoL) questionnaire, and adverse event were assessed at 2, 4, 8, and 12 weeks. Findings: Of the 288 patients, 247 patients, with 117 patients in the placebo control group and 130 patients in the urea cream group, were analyzed. The urea cream group showed lower cumulative incidence of any grade of HFSR (Log-rank, p=0.247) and severe HFSR of grade 2 or higher (Log-rank, p = 0.394) without statistical significance. In the incidence by time point, the development of severe HFSR of grade 2 or higher was significantly lower in the urea cream group than in the placebo control group at two weeks (13.8% vs. 23.9%, p=0.042). The urea cream group showed a significantly improved questionnaire score compared to the placebo control group (11.8 vs. 19.7, p=0.014) at 12 weeks. Interpretation: Treatment with urea cream showed a lower incidence of severe sorafenib-induced HFSR at 2 weeks and reduced the tendency of HFSR development in HCC patients. Therefore, treatment with urea cream could be considered for prophylaxis or improvement of HFSR grade in HCC patients treated with sorafenib. Trial Registration: This study was registered at ClinicalTrial.gov (NCT03212625). Funding Statement: The Korea Liver Cancer Association and Hanmi Pharmacy (IIT-CAV-004). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All participants provided written informed consent. This study was approved by the institutional review board of each participating institute (2016GR0350).

Drug reactions resulting from chemotherapy agents are common and frequently affect the skin. Although often benign, a select few of these cutaneous reactions may necessitate immediate changes to the antineoplastic regimens. Given the diversity of chemotherapeutic skin reactions and their complex implications on patient management, an organized conceptual schema is imperative for proper patient care. We evaluate a number of commonly seen chemotherapy-induced skin toxicities organized by pathogenic mechanism and drug class, providing a framework for the identification and categorization of adverse events to prevent unrecognition. Groupings of these reactions include direct cytotoxicity and/or drug accumulation, immunologic hypersensitivity, and aberrant molecular signaling.

Aim This study investigates the prophylactic effect of henna on the occurrence of hand-foot syndrome (HFS) in patients receiving capecitabine for breast and colorectal cancer. Method This experimental study was carried out between May 2014 and May 2015. In this self-control experimental study, 52 patients with breast and colorectal cancer were included on the first day of capecitabine treatment and had a minimum follow-up of 3 cycles. One hand/foot of each patient constituted the study hand/foot, whereas the others constituted the control. Henna was administered to the study hand/foot on the first day of treatment and application renewed weekly. Development of grade 1-3 toxicity was set as the termination criterion for study. Results Painful skin changes such as rawness, intumescence and bulla formation, blocking the daily activities or self-care were observed in 26.9% of the patients in the 3rd or 4th cycles of treatment. Development time and severity of skin changes over time did not differ significantly between the study and the control hand/foot. Conclusion Further studies with a larger sample size are needed to conclude on the prophylactic effect of henna in the management of the HFS.

Lessons Learned A structured teaching module including intensive prophylactic measures to alleviate hand-foot syndrome (HFS) during capecitabine therapy is feasible but ineffective at protecting patients from HFS. Pharmacologic therapeutic interventions should be investigated for the management of this complication. Background Capecitabine-induced hand-foot syndrome (HFS) has a detrimental effect on quality of life. The effect of a structured teaching module including intensive prophylactic measures was evaluated. Methods This non-crossover phase III double-blinded clinical trial randomized patients in a 1:1 ratio to either a control group or to a group administered a structured teaching model including intensive prophylactic measures on HFS administered by a trained oncology nurse at regular intervals (case) versus standard information on HFS care administered by treating clinician (control). The primary endpoint was comparison of fraction of patients in both arms developing at least grade 2 HFS. Results Between June 15, 2016, and April 4, 2018, 280 patients (140 to case and 140 to control) were enrolled. The median number of capecitabine chemotherapy cycles was eight; 269 patients (96%) were evaluable for HFS, of whom 89 patients (33.08%) developed at least grade 2 HFS (grade 2 HFS, 73 patients [26.1%]; grade 3 HFS, 16 patients (5.7%}). There was no difference in at least grade 2 HFS between evaluable case and control arms of the study (control group, 45/135 [33.3%]; case, 44/134 [32.8%]; p = .93). Conclusion The use of a structured teaching module including intensive prophylactic measures was feasible, but this did not reduce the incidence and severity of capecitabine-induced HFS.

Multiple randomized controlled trials have assessed hand-foot skin reaction (HFSR) caused by vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs).We performed a meta-analysis to determine the incidence and the relative risk (RR) of HFSR associated with these agents.Databases were searched for relevant studies. Statistical analyses were conducted to calculate the summary incidences, RR, and 95% confidence intervals (CIs) by using random-effects or fixed-effects models according to the heterogeneity of the included studies.A total of 24,956 patients from 57 studies were included. The overall incidence of all-grade and high-grade HFSR associated with VEGFR-TKIs was 35.0% (95% CI, 28.6%-41.6%) and 9.7% (95% CI, 7.3%-12.3%), respectively. The use of VEGFR-TKIs significantly increased the risk of developing all-grade (RR, 5.09; 95% CI, 3.52-7.35; P .001) and high-grade (RR, 9.42; 95% CI, 5.59-15.90; P .001) HFSR. Subgroup analyses revealed that the risk of HFSR was significantly increased according to tumor type, VEGFR-TKI, trial phase, treatment regimen, and control therapy. No evidence of publication bias was observed.High heterogeneity in most studies.High risk of HFSR is prone to develop in cancer patients receiving VEGFR-TKIs.

Background This study aimed to evaluate the efficacy and safety of apatinib with a low dose of 250 mg/d in the treatment of platinum‐resistant or platinum‐refractory ovarian cancer patients. Methods Patients with platinum‐resistant or platinum‐refractory ovarian carcinoma treated with 250 mg/d apatinib in our institution from November 2016 to December 2017 were retrospectively reviewed. The tumor response and progression were evaluated according to the standard by incorporating the levels of CA125 and Response Evaluation Criteria in Solid Tumors 1.1. CTCAE 4.03 was used to evaluate adverse events (AEs). Results Fifty‐two eligible patients were enrolled in per‐protocol (PP) analysis and 65 patients (including 13 lost to follow‐up) were included in the intention‐to‐treat (ITT) analysis. In PP analysis, 18 patients (34.6%) had partial response (PR), 22 patients (42.3%) had stable disease (SD), and the disease control rate (DCR) was 61.5%. Median progression‐free survival (PFS) was 4.0 months (95% CI, 2.83‐5.17 m), and median overall survival (OS) was 25.33 months (95% CI, 17.74‐32.92 m). The objective response rate and DCR for patients in ITT analysis were 27.7% and 49.2%, respectively. The top three treatment‐related AEs were hypertension, hand‐foot syndrome, and leukopenia. Eight patients (15.4%) in PP population had grade 3 treatment‐related AEs. Previous chemotherapy lines, number of recurrences, and AEs did not affect the efficacy of apatinib. Age older than 60 was associated with higher rates of disease control and prolonged PFS (P, Apatinib 250 mg/day is a feasible treatment in patients with platinum‐resistant or platinum‐refractory EOC.

Background Breast cancer patients may experience an increased chance of survival with adjuvant chemotherapy. However dermatologic adverse effects can cause major discomfort due to physical or cosmetic problems. This study aims to describe dermatologic complications in breast cancer patients during chemotherapy. Methods This longitudinal prospective observational study included data on women with non-metastatic breast cancer whom were treated with AC-T protocol (anthracycline, cyclophosphamide, and taxane) adjuvant chemotherapy and consecutively enrolled during two years. The study was performed in an educational and tertiary referral center. The patients' information including age, body mass index (BMI), past medical history, and different dermatologic complications were collected for all participants. Results Of 190 enrolled women, all patients experienced alopecia, which occurred in 131 patients (68.9%) after the first cycle. Skin, mucosal, and nail involvement were respectively seen in 46 (24.2%), 51 (26.8%), and 86 (45.2%) cases. Cutaneous complications were observed mainly between the third and sixth chemotherapy cycles. Palmoplantar erythema and palmoplantar dysesthesia were the most common cutaneous complications. Dermatologic adverse effects were significantly more frequent in the patients with an underlying disease. Conclusion These findings suggest that dermatologic adverse effects of adjuvant chemotherapy are common and could be induced by all components of AC-T regimen. These complications should be skillfully managed to increase patients' comfort.

Introduction: Capecitabine is an oral chemotherapy frequently used in the treatment of metastatic breast and colorectal cancers. Drug-induced cutaneous hyperpigmentation is a rare adverse effect of capecitabine, which is almost exclusively reported with development of hand-foot syndrome (HFS). Here, we report a case of capecitabine-induced hyperpigmentation affecting the hands, feet, face, and tongue in the complete absence of HFS.Case report: An 82-year old man presented with progressive hyperpigmentation of his hands, feet, face, and tongue shortly after initiating capecitabine for treatment of colon adenocarcinoma. There was no associated erythema, edema, blistering, desquamation, tingling, or tenderness. After completion of capecitabine therapy, he endorsed 95% resolution of all hyperpigmentation.Discussion: Previous reports of capecitabine-induced hyperpigmentation have argued that it may be a sign of impending toxicity and should be a part of the HFS grading scale. Others argue that the two are separate entities, yet the mechanism is still unknown. This case supports that capecitabine can cause hyperpigmentation independent of HFS, and thus, should be evaluated as a separate entity of HFS if other symptoms are lacking.

Capecitabine is a widely used 5-fluorouracil oral prodrug. Hand-foot syndrome (HFS), one of the most common adverse events of capecitabine, impacts patients’ quality of life seriously. The pathogenesis of HFS remains unclear but was usually considered as a type of inflammation conducted by cyclooxygenase-2 (COX-2). The COX-2/PGES/EP signaling pathway plays an important role in the inflammatory reaction. We hypothesized that the single nucleotide polymorphisms (SNPs) in this pathway may be associated with the risk of HFS induced by capecitabine. Using DNA from blood samples of 225 patients, we genotyped 19 SNPs in 6 core genes (COX-2, PGES, EP1, EP2, EP3, and EP4). Common Terminology Criteria for Adverse Events version 3.0 was used to grade hand-foot syndrome. We used logistic regression analysis to evaluate the correlations between genotype variants and occurrence of HFS. The cumulative incidence of HFS was assessed by Kaplan–Meier analysis. Among the 225 participants, 58.6% (132/225) patients developed into HFS, including 41.3% (93/225) grade 1 HFS, 10.2% (23/225) grade 2 HFS and 7.1% (16/225) grade 3 HFS. Multivariate logistic regression analysis showed the AG/GG genotype of rs3810255 to be associated with a significantly higher risk of grade 2/3 HFS, while the AG/AA genotype of rs17131450 to be associated with a significantly lower risk of grade 2/3 HFS (OR = 3.646, P = 0.011; and OR = 0.266, P = 0.036; respectively). Our study showed that rs3810255 AG/GG genotypes and rs17131450 GG genotypes to be associated with high risk of capecitabine-induced HFS.

Background: This study aimed to investigate the impact of early adverse events (AE) following the initiation of lapatinib plus capecitabine on the progression-free survival (PFS) and overall survival (OS) outcomes of human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer (ABC) patients. Methods: A secondary analysis of participants treated with lapatinib plus capecitabine, or ado-trastuzumab emtansine in the clinical trial EMILIA was conducted. Cox proportional hazard analysis was used to assess the impact of AE occurring within the first 42 days of lapatinib plus capecitabine therapy on the PFS and OS outcomes of ABC patients. Results: The study included 488 HER2-positive (ABC) patients initiated on lapatinib plus capecitabine. Rash (Hazard Ratio (HR) [95% Confidence Interval (CI)]: Grade 1 = 0.67 [0.46-0.98], Grade 2+ = 0.71 [0.42-1.19]; p = 0.046) and hand-foot syndrome (HR [95% CI]: Grade 1 = 0.58 [0.43-0.80], Grade 2+ = 0.61 [0.43-0.86]; p =

A 79-year old male was admitted to hospital for weight loss and polyarthritis. Examination revealed warmth, erythema and swelling of the left metacarpophalangeal joints, wrist, right shoulder and ankle. The CRP was elevated at 109 mg/L (ULN

A 60-year-old male presented with skin lesions on the limbs of both the extremities, nature of which is hyperchromatic, scaly in nature which was considered as Chronic Lichenoid Dermatoses. The patient was on treatment with Sorafenib for Hepato-Cellular Carcinoma.

Acral lesions are well-known physical findings in various infectious disorders. Although they are often overlooked, they can be the key to the diagnosis of the underlying disease. Considering this, we present an overview of various infectious causes of acral lesions in childhood. In addition, we discuss their characteristic presentation, evolution, and appropriate treatment. To our knowledge, this is the first review covering viral, bacterial and mycotic causes.

Purpose In clinical practice, the risk factors for pegylated liposomal doxorubicin-related hand-foot syndrome remain unclear. The purpose of this study was to determine the risk factors associated with hand-foot syndrome in patients with lymphoma using pegylated liposomal doxorubicin. Methods This retrospective descriptive analysis included patients with lymphoma who received PLD treatment (≥ 2 cycles of chemotherapy) at our cancer centre and had complete follow-up data from January 2016 to February 2020. Clinical, laboratory data, as well as the occurrence of hand-foot syndrome (incidence, location, severity, impact on follow-up chemotherapy) were obtained. The primary end point was the incidence of hand-foot syndrome, which was classified according to the “Common Terminology Criteria for Adverse Events” (Version 4.0). A multivariate logistic regression analysis was used to identify risk factors for hand-foot syndrome in patients with lymphoma using doxorubicin liposomes. Findings A total of 167 patients met the inclusion criteria. 58 developed HFS, of which 45 occurred after the second course of chemotherapy. The multivariate logistic regression analysis revealed that a dose increase of pegylated liposomal doxorubicin and hepatobiliary dysfunction were significantly associated with an increased risk for hand-foot syndrome(dose intensity, OR = 6.479; 95% CI, 1.431–29.331 [P = 0.015]; history of gallstones, OR = 14.144, 95% CI, 1.512–132.346 [P = 0.020]; alanine aminotransferase, OR = 1.194, 95% CI, 1.056–1.350 [P = 0.005]; aspartate aminotransferase, OR = 1.162, 95% CI, 1.010–1.336 [P = 0.035]; and glutamine transpeptidase, OR = 1.092, 95% CI, 1.016–1.174 [P = 0.018]). Implications These findings contribute to the risk assessment of patients with lymphoma before using pegylated liposomal doxorubicin. For patients with the above risk factors, preventive measures should be taken in advance to reduce the incidence of HFS.

Hand-foot syndrome (HFS) is a frequent adverse effect of various anti-tumour drugs, such as capecitabine, that affects their dose-limiting toxicity. The mechanism of HFS remains unknown and there are currently no effective strategies to treat HFS, except for cessation. The current study presented a female case where one hand, affected by brachial plexus infiltration due to the subclavian lymph node metastasis of breast cancer, exhibited not only pain and partial motor paralysis but also anhidrosis, oedema and skin colour changes. The patient met the diagnostic criteria for complex regional pain syndrome (CRPS). After treatment with capecitabine, their anhidrosis hand completely prevented HFS. The other hand and both feet demonstrated typical symptoms of HFS, which improved consequent to capecitabine cessation. The CRPS-affected hand remained normal. Considering the limited presentation of HFS concomitant with anhidrosis, the exocrine release of condensed capecitabine through sweat glands might be a promising mechanism of HFS induction.

Introduction Adermatoglyphia is defined as the medical condition clinically diagnosed to those who have a congenital or acquired loss of the epidermal ridges on the fingertips, commonly known as fingerprints. Capecitabine, a fluoropyrimidine, is the treatment of choice in a myriad of tumors and has occasionally been reported to cause adermatoglyphia as a secondary effect upon its use. Case Report A 52-year-old female patient, diagnosed with stage IV metastatic left breast cancer with extension to bone in late 2011 reported upon biopsy a hormone receptor positive Her2 negative ductal carcinoma. After initial treatment with a combined radiotherapy and chemotherapy palliative treatment, hepatic and lung metastasis progression obliged capecitabine oral intake. In 2018, after two years on the fluoropyrimidine (capecitabine), the patient reported adermatoglyphia. Management & Outcome The patient opted to continue taking the medication, since such treatment was working with no other meaningful side effects. Her last work-up studies continue to show complete lung and liver response with stable bone disease. Discussion Capecitabine is a common drug in the therapy against metastatic breast cancer due to its manageable safety profile. Hand-foot syndrome is a frequent side effect caused by this drug, with dosage adjustment recommended with progression of symptoms. Recent publications have reported adermatoglyphia as a rare side effect of capecitabine use. Upon further examination through dermatoscopy and biopsy, the patient was evidenced to have lost the epidermal ridges that form fingerprints. A score of 9 on the Naranjo scale confirmed to be a consequence of the administration of capecitabine.

Introduction This study aimed to evaluate the frequency of nail disorders and the presence of fungi on the nails of the hands and feet of patients with hand-foot syndrome secondary to treatment with paclitaxel. Methods Prospective study, carried out from October 2018 to December 2019, which included 81 patients undergoing treatment for breast cancer using paclitaxel and had signs and or symptoms of hand-foot syndrome with or without nail disorders. The data were collected through interviews guided by a structured questionnaire, information from medical records and reports of mycological exams. Results The average age of women was 54.7 ± 7.4 years. Nail disorders occurred in 69 patients (85.2%), and of these, 43 (62.3%) were positive for fungi. The fungi were yeasts ( n = 38; 69%), dermatophytes ( n = 15; 27.2%) and non-dermatophyte filamentous fungi ( n = 8; 14.5%). Conclusions Nail disorders were the most frequent manifestations in patients with hand-foot syndrome treated with paclitaxel and occurred in 85.2% of them. It was evidenced that fungi are present on the nails of these patients and can occur in up to 65.28%. The most prevalent fungi were Candida and Trichophyton. The nail lesion was associated with the type of treatment protocol used by the patient. The results of the study point to the need to select safe management alternatives for patients, so they can prevent nail lesions and prevent the proliferation of fungi, consequently reducing negative life impact during treatment.

Objetivou-se identificar na literatura o desenvolvimento da Síndrome Mão-Pé, como efeito adverso à utilização de quimioterápicos. Revisão integrativa realizada nas bases de dados LILACS, BDENF, PubMed e na biblioteca virtual ScienceDirect, nos idiomas português, inglês e espanhol. Ensaios clínicos publicados com recorte temporal de 2016 a 2021, centrados no público adulto, foram selecionados e segregados em dois tópicos. As informações foram tabuladas no programa Microsoft Excel® 2010 e processadas a partir de estratégia: média aritmética descritiva simples, frequência absoluta e relativa. Encontrou-se 559 artigos, após aplicação dos critérios de inclusão e exclusão, 20 estudos foram eleitos para compor a amostra final. A classe farmacológica mais elencada como potencializadora da Síndrome Mão Pé (SMP) foi à fluoropirimidinas (80%). Mediante às manifestações clínicas apresentadas na síndrome, impactos negativos perpetuam na rotina dos pacientes, pois a execução das atividades de vida diária é comprometida, para minimizar os danos causados por esta afecção, métodos terapêuticos foram salientados, estes são aplicados para redução de graus da síndrome e melhor qualidade de vida. Em síntese, percebe-se que, a utilização de quimioterápicos melhora o prognóstico oncológico, entretanto acarreta algumas reações adversas recorrentes, dentre estas, a SMP, cujas manifestações não são ameaçadoras à vida, mas as limitações desencadeadas inferem prejuízos no autocuidado e a qualidade de vida torna-se insatisfatória.

Background Hand-foot syndrome (HFS) is a specific adverse effect of certain chemotherapy that may lead to dosage reduction or chemotherapy discontinuation in patients with cancer. Topical urea cream may reduce symptom severity in patients with HFS. However, these studies have not provided consonant results. Objective To determine the effectiveness of urea cream, we conducted a meta-analysis of clinical trials to evaluate the prevention and treatment of HFS. Methods PubMed, EMBASE, and Cochrane Library databases were searched for studies published before September 2020. The study registered at PROSPERO (CRD 42020203164). Incidence of HFS reported in studies at any grade and at second grade or greater was assessed within 3 to 12 weeks. Secondary outcomes were time to HFS, incidence of skin-related adverse events, chemotherapy dose reduction, and quality of life. Results Seven trials involving 1387 patients were reviewed. In the prophylactic subgroup, patients with urea cream intervention showed a significantly lower incidence of HFS at second grade or greater (risk ratio, 0.72; 95% confidence interval, 0.58-0.90) and a nonsignificant lower incidence of any-grade HFS (risk ratio, 0.79; 95% confidence interval, 0.58-1.08) than those not receiving urea cream intervention. Conclusions Urea cream has advantages to reduce the incidence of severe HFS. Implications for practice Urea cream is a safe and viable topical prevention strategy that can reduce the incidence of high-grade HFS in patients undergoing chemotherapy. We recommend a routine treatment option before chemotherapy for the patients.

Hand-foot syndrome (HFS) is a common capecitabine-based chemotherapy-related adverse event (CRAE) in patients with colorectal cancer (CRC). It is of great significance to comprehensively identify susceptible factors for HFS, and further to elucidate the biomolecular mechanism of HFS susceptibility. We performed an untargeted multi-omics analysis integrating DNA methylation, transcriptome, and metabolome data of 63 Chinese CRC patients who had complete CRAE records during capecitabine-based chemotherapy. We found that the metabolome changes for each of matched plasma, urine, and normal colorectal tissue (CRT) in relation to HFS were characterized by chronic tissue damage, which was indicated by reduced nucleotide salvage, elevated spermine level, and increased production of endogenous cytotoxic metabolites. HFS-related transcriptome changes of CRT showed an overall suppressed inflammation profile but increased M2 macrophage polarization. HFS-related DNA methylation of CRT presented gene-specific hypermethylation on genes mainly for collagen formation. The hypermethylation was accumulated in the opensea and shore regions, which elicited a positive effect on gene expression. Additionally, we developed and validated models combining relevant biomarkers showing reasonably good discrimination performance with the area under the receiver operating characteristic curve values from 0.833 to 0.955. Our results demonstrated that the multi-omics variations associated with a profibrotic phenotype were closely related to HFS susceptibility. HFS-related biomolecular variations in CRT contributed more to the relevant biomolecular mechanism of HFS than in plasma and urine. Spermine-related DNA hypermethylation and elevated expression of genes for collagen formation were closely associated with HFS susceptibility. These findings provided new insights into the susceptible factors for chemotherapy-induced HFS, which can promote the implementation of individualized treatment against HFS.

Although paclitaxel is known to cause mild skin toxicity, it may induce severe HFS requiring drug withdrawal. Patients with high disease burden might receive prolonged paclitaxel chemotherapy. Hence, a grade 2 toxicity would better indicate withdrawal of paclitaxel instead of suspension and rechallenge, to prevent such severe HFS requiring long‐time recovery., Although paclitaxel is known to cause mild skin toxicity, it may induce severe HFS requiring drug withdrawal. Patients with high disease burden might receive prolonged paclitaxel chemotherapy. Therefore, a grade 2 toxicity would better indicate withdrawal of paclitaxel instead of temporary suspension to prevent such severe HFS requiring long‐time recovery.

Purpose: As a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), apatinib has shown a survival benefit in multiple solid tumors. This study aims to evaluate the efficacy and safety of apatinib in patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy. Methods: A total of 42 patients between June 2018 and March 2019 were involved in this study. All patients orally received apatinib once daily in a 4-week cycle until disease progression or adverse events that prohibit further therapy. The primary endpoint was progression-free survival (PFS), the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), health-related quality of life (HRQoL) and adverse events. Results: During a median follow-up of 13 months, 8 patients achieved a partial response and 24 cases achieved stable disease. None of them reported a complete response. The ORR and DCR were 19.0 and 76.2%, respectively. The median PFS was 6.0 months (95% CI 4.9–7.1), and the median OS was 12.0 months (95% CI 10.1–13.9). The global health score/HRQoL improved significantly following 3-cycle treatment (50.4 ± 12.5 vs. 60.1 ± 11.8; p < 0.01). The most frequent grade 3–4 adverse events were hand-foot syndrome, hypertension and fatigue. Conclusion: Apatinib should be an effective and tolerable treatment option for patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy.

Purpose Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery. Methods A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (n = 52) or the placebo group (n = 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale. Results There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%, p = 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%, p = 0.185, 67.3% vs. 80.0%, p = 0.124, respectively). Conclusion This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS. Trial registration UMIN000024784

Introduction: Sorafenib is a multitargeted tyrosine kinase inhibitor, which has been mainly used in the treatment of advanced hepatocellular carcinoma and renal cancer. However, hand-foot skin reaction (HFSR), as one of the most common adverse reactions, have hindered its long-term clinical application. At present, the mechanism of its occurrence has not been clearly studied and it leads to the lack of effective means of intervention. This article reviews known mechanism and management methods of HFSR caused by sorafenib.Areas covered: The author reviews HFSR caused by the treatment of sorafenib including the mechanism and management. English language reports located through PubMed are reviewed.Expert opinion: There are some conjectures about the mechanism of HFSR. However, the mechanism of HFSR induced by sorafenib is still unclear at present. In the absence of understanding the mechanism of HFSR, the most common method for clinical treatment of sorafenib-induced HFSR is dose down-regulation or discontinuation of treatment, which affects efficacy and even survival. Future research should focus on the mechanism of HFSR to find out new ways for prevention. Precautionary measures before the occurrence of HFSR can also be studied in the future.

BackgroundSmall-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies.MethodsEligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate.ResultsForty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand–foot syndrome, increased L-gamma-glutamyltransferase.ConclusionsApatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted.Trial registrationNCT02945852.

Hand-foot syndrome (palmoplantar erythrodysesthesia, palmar-plantar erythema, toxic erythema of the palms and soles, or Burgdorf’s syndrome) is characterized by painful predominantly palmoplantar lesions with the association of different chemotherapeutic agents. More recently, hand-foot skin reaction has been reported to be associated with regimens using targeted agents, in particular the multikinase inhibitors. Hand-foot syndrome/skin reaction has a major impact on patient’s quality of life, necessitating dose reduction or treatment interruption. In this article, hand-foot syndrome and hand-foot skin reaction were discussed through patients consulted our dermatology outpatient clinic.

There is no standard treatment strategy for patients with extensive-stage small cell lung cancer (SCLC) who have failed two or more prior chemotherapeutic regimens. In this study, we retrospectively evaluated the efficacy and safety of apatinib in patients with extensive-stage SCLC after failure of more than second-line chemotherapy. A study group comprised of 22 patients with extensive-stage SCLC after failure of more than two prior chemotherapeutic regimens was given apatinib orally at an initial dose of 500 mg daily until disease progression or unacceptable toxicity. This study was analyzed according to the National Cancer Institute Common Toxicity Criteria for adverse events (AEs) and Response Evaluation Criteria in Solid Tumors (RECIST) for response assessment. Between August 30, 2015, and May 26, 2017, 22 patients were enrolled for evaluating the efficacy and safety of apatinib. Among them, 12/22 (54.5%) underwent dose reduction during treatment. Up to July 31, 2018, the median progression-free survival rate was 135.0 days [95% confidence interval (CI) 63.8–206.2]. According to the RECIST criteria, the disease control rate (DCR) was 86.4%, 19/22 [comprised of partial response (PR) 18.2%, 4/22; and stable disease (SD) 68.2%, 15/22 patients]. The most frequent AEs were hand–foot syndrome (45.5%, 10/22), secondary hypertension (45.5%, 10/22) and fatigue (40.9%, 9/22). The primary grade 3 or 4 toxicities were hypertension (22.7%, 5/22), hand–foot syndrome (13.6%, 3/22), and proteinuria (9.1%, 2/22). Apatinib exhibits modest activity and acceptable toxicity for patients with heavily pretreated extensive-stage SCLC.

Purpose The objective of this qualitative study was to understand the perceived needs of advanced-stage cancer patients with chemotherapy-related hand-foot syndrome (HFS) and/or targeted therapy-related hand-foot skin reaction (HFSR). Method Face-to-face interviews were conducted with 20 outpatients with advanced/recurrent cancer and chemotherapy-related HFS and/or targeted therapy-related HFSR using a semi-structured interview guide at Keio University Hospital, Tokyo, Japan. Thematic analysis was used to analyse the data. Results The unmet needs of cancer patients with chemotherapy-related HFS and/or targeted therapy-related HFSR was identified through four themes: a sense of helplessness with persistent symptoms, noticeable appearance as a barrier to social participation, decreased willingness to work and continue treatment, and need of individual coping strategies. Conclusion This study revealed unmet needs of cancer patients with chemotherapy-related HFS and/or targeted therapy-related HFSR that are not often voiced. Health care providers should provide full information in advance and find the best coping strategy for individual patients.

Renal cell carcinoma (RCC) is the most common primary renal neoplasm. About a half of our patients relapse after primary treatment. We present here a case of RCC with solitary metastasis to the pleura which occurred 32 years after nephrectomy. Our patient is an 86-year-old male who presented to us with a cough of 2 months and a history of having undergone a right nephrectomy 32 years back. Imaging of the chest showed left pleural effusion with a left pleural nodule. Computed tomography-guided fine-needle aspiration cytology from the pleural nodule was suggestive of malignancy with a clear cell morphology, suggestive of clear cell RCC. The patient was started on sunitinib 25 mg once daily. After the 1st month, the patient's performance status improved markedly, with no cough and improved appetite. He had developed Grade II hand-foot syndrome, which was managed conservatively, and the dose was deescalated to 25 mg once daily - 5 days on and 2 days off. An X-ray of the chest taken 6 weeks after the start of therapy showed complete resolution of the pleural fluid and regression of the pleural nodule. The patient is alive and well 5 years into therapy. The case highlights the unusual propensity for very late metastasis in RCC. Metastasis after 30 years is extremely rare. Another highlight of the case is the good tolerability of the dose-modified schedule of sunitinib. Wise patient selection and dose modification can certainly add "life to the years" in our very elderly patients.

Background: Capecitabine is a prodrug of 5-fluorouracil (5-FU) and is converted to 5-FU in tumor tissue. Its primary mechanism of action is the suppression of DNA synthesis via inhibition of thymidylate synthetase. It is mostly used for neoadjuvant chemoradiation, adjuvant chemotherapy for colorectal cancer, metastatic breast, and localized and metastatic gastric cancer, among others. Adverse effects of capecitabine include diarrhea, hand-foot syndrome (HFS), pancytopenia, stomatitis, increased bilirubin, nausea, vomiting, and very rarely adermatoglyphia. Dermatoglyphics refers to fingerprints. Adermatoglyphia refers to the loss of fingerprints. Case review summary: We report the case of a 62-year-old male patient known case of locally advanced colorectal cancer. He presented in the clinic with residual disease after initially being treated with local surgery and chemoradiation with 5-FU. Positron emission tomography (PET) scan done at the time of presentation showed locally advanced disease. He was managed with surgery followed by chemotherapy with oxaliplatin 130 mg/m2 and capecitabine (Xeloda) 1500 mg twice a day for two weeks via three weekly cycles. Post cycle five, the patient complained of grade I HFS symptoms and inability to open a bank account due to loss of fingerprints. The patient was oblivious about this condition before that. After completing his adjuvant treatment that is six cycles of oxaliplatin and Xeloda, his symptoms of the HFS and loss of fingerprints, improved. Conclusion: As this case describes, adermatoglypia is a rare but noticeably side effect of capecitabine with a high chance of reversibility. Similar case reports have been reported with some normalization of fingerprints, after stopping treatment. Fingerprints have been used for centuries as means of identification in banks, aviation, immigration, computers, and mobile phones, amongst others. Awareness regarding the loss of fingerprints due to capecitabine is important for the patient and clinician, and alternative means of identification or other adaptive methods of recognition should be used for these patients.