Severity Of Hand-foot Syndrome Research Articles

A Randomized Single-Blinded Phase II Trial Comparing Efficacy and Quality of Life of Topical Aloe Vera Gel Plus Urea Cream Versus Urea Cream Alone for Prevention of Hand Foot Syndrome in Cancer Patients Receiving Capecitabine.

Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively co-prescribed, even though its efficacy is doubtful. Aloe vera gel with urea cream might potentiate each other. This trial was intended to prove the efficacy of this combination. The investigators conducted a randomized single-blinded phase II study. The participants were randomized 1:1 to receive the combination of aloe vera gel and 10% urea cream (n = 30), the experimental A+U arm and 10% urea cream alone (n = 31), the U arm. The sample size was calculated to have 90% power to show the significant 20% reduction in the incidence of HFS grade 2-3 of the combination therapy with alpha level = 0.05. Both the CTCAE criteria version 5 and the dermatology life quality index (DLQI) were assessed to determine the severity of HFS and quality of life, respectively. Most of the participants had rectal cancer (A+U: 43.3%; U: 41.9%). In the A+U group, 86.7% had grade 0-1 HFS and 13.3% had grade 2-3 HFS. In the U group, 64.5% had grade 0-1 HFS and 35.5% had grade 2-3 HFS (Mann-Whitney U test, p = 0.045). Grade 2-3 HFS was significantly lower in the combination group. Combination of aloe vera gel and 10% urea cream ameliorated the severity of HFS in participants taking capecitabine; however, no significant difference in DLQI between the groups was demonstrated.

Incidence and severity of hand-foot syndrome in cancer patients receiving infusional 5-fluorouracil or oral capecitabine-containing chemotherapy regimens.

Hand-foot syndrome is a common adverse effect of 5-fluorouracil infusion or oral capecitabine. Several types of research have shown that clinical presentations of hand-foot syndrome vary by ethnicity, so we tried to look at the incidence and severity of hand-foot syndrome in individuals receiving infusional 5-fluorouracil or oral capecitabine at a tertiary care hospital in central Kerala, India. To determine the incidence and severity of hand-foot syndrome in cancer patients receiving infusional 5-fluorouracil or oral capecitabine chemotherapy regimen. A prospective cohort study was conducted at the oncology department of a tertiary care hospital in Kerala, India. Our study subjects were those who underwent chemotherapy with infusional 5-fluorouracil or oral capecitabine and later developed hand-foot syndrome. The patients who developed hand-foot syndrome after chemotherapy were assessed to determine the incidence of hand-foot syndrome. Also, the severity of hand-foot syndrome among cancer patients was estimated using CTCAE version 5.0. Out of 104 study participants, 76.90% (N = 80) of the patients had hand-foot syndrome, whereas 23.07% (N = 24) did not. The onset of hand-foot syndrome symptoms varied depending on the patient. Most patients (60%) displayed grade-one symptoms in their third cycle. The remaining patients showed grade-one symptoms in cycle one (3.75%), cycle two (17.5%), and cycle four (18.75%). The study also showed t no association between the incidence of hand-foot syndrome and the type of regimen. The majority of the patients suffered from hand-foot syndrome. As well, most of the patients were afflicted by grade one hand-foot syndrome.

The preventive effect of celecoxib on regorafenib-associated hand-foot syndrome in patients with liver metastasis from colorectal cancer: A single-center, retrospective, real-world study.

e15576 Background: Regorafenib, an oral multi-kinase inhibitor, is the third- or later-line therapy for colorectal cancer with liver metastasis (CRLM), but the hand-foot syndrome (HFS) is its most common adverse reaction. Celecoxib, a selective COX-2 inhibitor, can treat inflammation. This study aimed to explore whether additing celecoxib to the cancer therapy regorafenib can prevent or alleviate the HFS, improve drug tolerance, and prolong the patient’s survival. Methods: In the retrospective cohort analysis, patients with colorectal cancer and liver metastasis, to whom regorafenib and celecoxib were administered in the Department of Hepatopancreatobiliary Surgery of Beijing Cancer Hospital between November 2021 and October 2022, were included. Upon the medical records from physical examination and other means of follow-ups, the Kaplan-Meier estimator analyzed the survival function and the severity of adverse events was described according to the CTCAE v.5.0 standards. Results: Twenty-six patients were included in the analysis and 14 colorectal cancer patients had extrahepatic metastases at the onset of the treatment. All patients received regorafenib and celecoxib. Further, 15 patients were treated with a combination of immune checkpoint inhibitors, 3 patients underwent combined local-regional therapy, 1 patient received combined chemotherapy, and 7 patients received regorafenib. Among all the patients, the incidence of grades 1 & 2 HFS was 46% and no grade 3 HFS was observed. The other main adverse events were hoarseness (35%), fatigue (27%), rash (27%), and neutropenia (15%). The most frequent adverse events from the CONCUR study and current analysis are shown in Table 1. Five patients (19%) had their treatment interrupted or their drug dose reduced due to adverse events. The median follow-up time of all patients was 5.3 (range, 1.6-13.1) months, the overall survival was not reached, and the median progression free survival was 2.9 (95% CI: 1.5-4.3) months. As the overall response in all patients after treatment, 3 cases (12%) achieved PR, 11 cases (42%) had SD and 12 cases (46%) showed PD. Conclusions: The addition of celecoxib to the cancer-line therapy regorafenib in CRLM patients did not reduce the incidence of HFS, but reduced the severity of HFS (grade 3). Also, it did not shorten the survival time of the patients. The addition of celecoxib to the main therapy might alleviate some adverse effects. [Table: see text]

Two important factors affecting the prognosis of patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma

ObjectiveTo investigate the effects of hand–foot syndrome (HFS) and fatigue on disease progression and survival in patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma.MethodsA retrospective analysis of patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from 1 October 2018 to 31 October 2021 was performed, and clinical and pathological data and follow-up results were obtained. Patients were divided into groups according to the severity of HFS and fatigue. Survival analysis among the groups was performed using the Kaplan–Meier method, continuous variables were analyzed using the t-test, and factors associated with survival were evaluated using multivariate Cox regression analysis.ResultsThe study included 150 men and 23 women with a mean age of 60.77 years (range: 40–85 years). The median overall survival (OS), progression-free survival (PFS), and time to tumor progression (TTP) increased with increasing severity of HFS. Conversely, the median OS, PFS, and TTP decreased with increasing severity of fatigueConclusionHFS and fatigue were independent risk factors affecting TTP, PFS, and OS among patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma.

Predicting Response to Anthracyclines in Ovarian Cancer.

(1) Background: Anthracyclines are intriguing drugs, representing one of the cornerstones of both first and subsequent-lines of chemotherapy in ovarian cancer (OC). Their efficacy and mechanisms of action are related to the hot topics of OC clinical research, such as BRCA status and immunotherapy. Prediction of response to anthracyclines is challenging and no markers can predict certain therapeutic success. The current narrative review provides a summary of the clinical and biological mechanisms involved in the response to anthracyclines. (2) Methods: A MEDLINE search of the literature was performed, focusing on papers published in the last two decades. (3) Results and Conclusions: BRCA mutated tumors seem to show a higher response to anthracyclines compared to sporadic tumors and the severity of hand–foot syndrome and mucositis may be a predictive marker of PLD efficacy. CA125 can be a misleading marker of clinical response during treatment with anthracyclines, the response of which also appears to depend on OC histology. Immunochemistry, in particular HER-2 expression, could be of some help in predicting the response to such drugs, and high levels of mutated p53 appear after exposure to anthracyclines and impair their antitumor effect. Finally, organoids from OC are promising for drug testing and prediction of response to chemotherapy.

Topical henna and curcumin (Alpha®) ointment efficacy for prevention of capecitabine induced hand-foot syndrome: A randomized, triple-blinded, placebo-controlled clinical.

In this clinical trial, we evaluated Alpha® ointment efficacy in prevention of capecitabine induced hand-foot syndrome (HFS) in patients with gastrointestinal or breast cancers, for the first time. During this pilot, randomized, triple-blinded, placebo-controlled clinical trial, the effect of Alpha® ointment (Lawsonia inermis 3g and Curcuma longa 0.15g/ 30g) was assessed. It was applied on the palms and the soles, two times daily starting at the first day of chemotherapy for 4 consecutive courses. The severity of HFS was assessed at the end of the chemotherapy courses based on World Health Organization (WHO) scale and scored between 0-4. Ninety eligible patients were included randomly in the treatment or placebo group. Median WHO HFS grade was not significantly different between the two groups, during the follow-up period (P > 0.05). In the weekly assessment, the scores increased meaningfully in both the placebo and treatment groups, but there was a delay in HFS occurrence and deterioration in Alpha ointment group based on post hoc analysis. Administration of Alpha® ointment containing henna and curcumin could not significantly prevent capecitabine induced HFS during 4 courses of treatment, but can somewhat delay its occurrence in patients with gastrointestinal or breast cancer.

Long-Term Safety Data on S-1 Administered After Previous Intolerance to Capecitabine-Containing Systemic Treatment for Metastatic Colorectal Cancer

IntroductionThe oral fluoropyrimidine S-1 has shown comparable efficacy to capecitabine in Asian and some Western studies on metastatic colorectal cancer. S-1 is associated with a lower incidence of hand-foot syndrome (HFS) and cardiac toxicity. We assessed the long-term tolerability of S-1 in patients who discontinued capecitabine for reasons of HFS or cardiac toxicity. Patients and MethodsPatients with metastatic colorectal cancer who switched from capecitabine to S-1, given as monotherapy or in combination with other agents, were identified in a Dutch prospective cohort study (2016-2021). The incidence and severity of HFS, cardiotoxicity and other toxicities were assessed. ResultsForty-seven patients were identified. The median duration of capecitabine treatment was 81 days (range 4-454). In 19 patients (40%) a dose reduction was applied prior to switch to S-1. Reasons for discontinuation of capecitabine were HFS in 36 (77%) patients, coronary artery vasospasms in 10 (21%) patients, and gastrointestinal toxicities in 1 patient (2%). The median number of S-1 cycles was 6 (range 1-36). The median time between last dose of capecitabine and first dose of S-1 was 11 days (range 1-49). After switch to S-1, all patients with prior HFS developed a lower grade or complete resolution of symptoms, and in all other patients symptoms did not recur. Other S-1-related adverse events were limited to grade 1-2. Six patients (13%) discontinued S-1 due to either known fluoropyrimidine-related or bevacizumab-related toxicities. Switch to S-1 did not appear to compromise treatment efficacy. ConclusionS-1 is a valid alternative to capecitabine in case HFS or cardiotoxicity occurs.

Evaluation of the Preventive Effect of Regional Cooling Nursing on Hand Foot Syndrome Caused by Doxorubicin Hydrochloride Liposome

Purpose: To explore the preventive effect of Regional cooling comprehensive nursing on hand foot syndrome caused by pegylated liposomal doxorubicin (PLD). Method: Adopt overall sampling method. Patients who used the same adjuvant drugs from January to December 2020 were randomly divided into an intervention group and a control group. The patients in the two groups received routine nursing guidance and drug prevention for the use of amygdalin. The patients in the intervention group were required to take protective measures of Regional cooling during chemotherapy. The occurrence of hand foot syndrome during adriamycin liposome administration was compared between the two groups. Results: By comparing the adverse reactions of cases during Adriamycin Administration, the incidence rates of grade I, II and III hand foot syndrome in the control group were 28.8%, 7.6% and 27.5% respectively, and the incidence rates of grade I, II and III hand foot syndrome in the intervention group were 42.1%, 12.3% and 7.0% respectively, with statistical significance (P < 0.05). Conclusion: Regional cooling nursing and preventive behavior guidance can effectively reduce the severity of hand foot syndrome caused by adriamycin.

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.

Utility of cooling patches to prevent hand-foot syndrome caused by pegylated liposomal doxorubicin in breast cancer patients.

BACKGROUNDPegylated 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.AIMTo study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term.METHODSThis 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.RESULTSIn 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).CONCLUSIONCooling 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.

Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine.

TPS12135 Background: The pathophysiology of capecitabine induced hand-foot syndrome (HFS) includes activation of cyclooxygenase (COX)-2, leading to an upregulation of the inflammatory cascade. Prophylaxis with oral celecoxib was previously reported to be associated with a significantly lower frequency of HFS (grade 1 [29.0% vs. 72.0%, p &lt; 0.001] and grade 2 [11.8% vs. 30.0%, p=0.024]) (1). The findings were confirmed in a phase III trial (2). However, the associated systemic adverse events limit routine prophylactic use. Till date, no clinical trials have assessed the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in preventing HFS. Methods: In this investigator-initiated randomised phase III double-blind, placebo controlled, parallel group trial, a total of 264 patients with any stage breast or gastrointestinal cancer planned to receive capecitabine as a single agent or in combination with other chemotherapy will be randomised (1:1) to 1% topical diclofenac or placebo (base for 1% topical diclofenac) arm at a single tertiary care cancer centre in India. Randomization will be done by stratified (male vs female, and capecitabine mono therapy vs combination) permuted block method using a computer generated random sequence and allocation concealment will be done by using sealed opaque envelopes. In both the arms, patients will be asked to apply 1 fingertip unit (FTU) of topical medication on both surfaces of bilateral hands twice daily for a total duration of 12 weeks or till development of grade 2 or higher HFS, whichever is earlier. The primary objective is to compare the effect of topical diclofenac with placebo in preventing clinically significant HFS (incidence of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 2 or higher HFS). The secondary objectives include comparison of topical diclofenac with placebo on (i) incidence of NCI CTCv5.0 all grade HFS, (ii) time to develop grade ≥2 HFS from start of capecitabine, (iii) patient-reported outcomes using HFS-14 questionnaire (iv) adherence with topical application using self-reported adherence diary, (v) capecitabine dose reductions, delays and cessation due to HFS and (vi) safety profile (NCICTCv5.0). The tertiary correlative endpoint is to correlate the occurrence and severity of HFS with serum COX-2 levels and polymorphism of dihydropyrimidine dehydrogenase (DPPD) enzyme. The trial is registered at the Clinical Trial Registry of India (CTRI/2021/01/030592). Till date, we have enrolled 12/264 patients. (1) Zhang RX et al. J Cancer Res Clin Oncol. 2011;137(6):953-957. (2) Zhang RX et al. Annals of oncology. 2012;23(5):1348-1353. Clinical trial information: CTRI/2021/01/030592.

Pegylated liposomal doxorubicin-induced hand-foot syndrome predicted by serum metabolomic profiling and prevented by calcium dobesilate

Pegylated liposomal doxorubicin-induced hand-foot syndrome predicted by serum metabolomic profiling and prevented by calcium dobesilate

A study on the incidence and severity of hand-foot syndrome in cancer patients treated with capecitabine

A study on the incidence and severity of hand-foot syndrome in cancer patients treated with capecitabine

Hand-foot syndrome and survival in patients with advanced non-small-cell lung cancer receiving anlotinib: a subgroup analysis of data from the ALTER 0303 study.

The ALTER 0303 study showed that anlotinib can significantly improve overall survival (OS) compared with the placebo in advanced non-small-cell lung cancer (NSCLC). Hand-foot syndrome (HFS) is a common anlotinib-related adverse event. The aim of this study was to assess the association of HFS with clinical benefit. A subgroup analysis of patients treated with anlotinib from the ALTER 0303 study was performed. Our analysis assessed if the appearance of anlotinib-related HFS in the first 42days (second-cycle HFS) and at any time could produce better clinical benefits. In this study, 294 patients were treated with anlotinib. Of which, 129 patients had HFS at any time, and 76 patients developed HFS in the first 2 cycles. Patients who received anlotinib and developed HFS had significantly prolonged OS, progression-free survival (PFS) compared to those who did not develop HFS in the first 2 cycles (13.5vs8.7months, p = 0.001; adjusted hazard ratio (HR) 0.63 (95% confidence interval [CI] 0.44-0.89),p = 0.009; 5.8vs4.5months, p = 0.001; adjusted HR, 0.59 [0.43-0.81],p = 0.001). The significant OS and PFSbenefits for patients with HFS versus without were seen at any time (14.5vs7.3months, p = 0.000; adjusted HR, 0.50 [0.36-0.67],p = 0.000; 5.8vs4.2months, p = 0.000; adjusted HR, 0.49 [0.37-0.65],p = 0.000). In addition, the grade of severity of HFS was strongly correlated with OS (p = 0.000). Presence of HFS may be a potential clinical marker for the treatment of NSCLC with anlotinib.

Virtual Screening of Henna Compounds Library for Discovery of New Leads against Human Thymidine Phosphorylase, an Overexpressed Factor of Hand-Foot Syndrome

Background: Capecitabine is one of the most effective and successful drugs for the treatment of uterine and colorectal cancer which has been limited in use due to occurrence of handfoot syndrome (HFS). Overexpression of human thymidine phosphorylase enzyme is predicted to be one of the main causes of this syndrome. Thymidine phosphorylase enzyme is involved in many cancers and inflammatory diseases and pyrimidine nucleoside phosphorylase family is found in a variety of organisms. Results of clinical studies have shown that topical usage of henna plant (Lawsonia inermis from the family of Lythraceae) could reduce the severity of HFS. Methods: By using in silico methods on reported compounds of henna, the present study is aimed at finding phytochemicals and chemical groups with the potential to efficiently interact with and inhibit human thymidine phosphorylase. Various compounds (825) of henna from different chemical groups (138) were virtually screened by the interface to AutoDock in YASARA Software package, against the enzyme structure obtained from X-ray crystallography and refined by homology modeling methods. Results: By virtual screening, i.e. docking of candidate ligands into the determined active site of hTP, followed by applying the scoring function of binding affinity, 71 compounds (out of 825 compounds) were estimated to have the likelihood to bind to the protein with an interaction energy higher than 10 kcal/mol (Concerning the sign of “binding energies”, please refer to the Methods section). Conclusion: Finally, diosmetin-3'-O-β-D-glucopyranoside (#219) and monoglycosylated naphthalene were respectively selected as the most potent phytochemicals and chemical groups. Flavonoid-like compounds with appropriate interaction energy were also considered as the most probable inhibitors. More investigations on henna compounds, are needed in order to approve their effectiveness and also to explore more anti-cancer, anti-inflammatory, anti-angiogenesis and even antibiotics.

Skin-mucous membrane disorder and therapeutic effect of pegylated liposomal doxorubicin in recurrent ovarian cancer.

Hand-foot syndrome (HFS) induced by chemotherapy and molecule-targeting drugs is correlated with treatment efficacy. We conducted a retrospective analysis to evaluate the relationship between HFS and efficacy of pegylated liposomal doxorubicin (PLD) for recurrent ovarian cancer. Patients were treated with PLD between July 2009 and May 2014. We evaluated patient characteristics, incidence of adverse events, clinical benefit (rate of complete response, partial response, and stable disease), progression-free survival, and overall survival. Twenty-seven patients were included in the study. Median age was 63 years (range, 41-77 years). The median number of cycles of PLD was 3 (range, 1-6). The clinical benefit rate was 33.3%, and progressive disease was noted in 18 patients (66.7%). Median overall survival was 6.7 months (range, 1.1-41 months). Compared with patients with grade 0/1 HFS and oral mucositis, patients with grade 2-4 toxicity (n = 9, 33.3%) had a significantly higher rate of clinical benefit (11.1% vs 77.7%; P < 0.001) and a longer median overall survival (3.7 months vs 20.8 months; P < 0.001). Severity of HFS and mucositis may be a predictive marker of PLD efficacy. The prevention and management of HFS and mucositis are important for continued treatment.

Risks associated with sunitinib use and monitoring to improve patient outcomes

Risks associated with sunitinib use and monitoring to improve patient outcomes

The effect of seasonal variation and secretion of sunitinib in sweat on the development of hand–foot syndrome

Hand-foot syndrome (HFS) is a side effect of sunitinib with considerable impact on quality of life. Seasonal variation and hyperhydrosis are possibly correlated to occurrence of HFS. Therefore, we proposed to study the prevalence of HFS in different seasons retrospectively and to study the relationship between sunitinib sweat secretion and HFS prospectively. A retrospective cohort of 19 patients treated with sunitinib was used to determine seasonal prevalence of HFS. In a prospective study, sunitinib and N-desethyl sunitinib levels in sweat patches of 25 patients treated with sunitinib were quantified and correlated to severity of HFS. In the retrospective cohort, the patients suffered from more severe HFS during summertime compared with the rest of the year. In the prospective study, the cumulative amounts of sunitinib plus metabolite measured in the patches of the on-treatment phase (median 129.4 ng/patch) were higher than the off-treatment phase (median 39.5 ng/patch). A tendency was observed towards increasing amounts of drug per patch with increasing severity of HFS. Patients experienced more HFS in summer time compared to other seasons. However, no statistically significant correlation between sunitinib sweat secretion and severity of HFS could be demonstrated within our patient cohort.

Significant Association between Hand-Foot Syndrome and Efficacy of Capecitabine in Patients with Metastatic Breast Cancer

Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), is a promising treatment for colorectal, breast and gastric cancers, but often causes hand-foot syndrome (HFS), the most common dose-limiting toxicity. The current study was conducted to investigate the relationship between HFS and efficacy of capecitabine in 98 patients with metastatic breast cancer. Possible associations between HFS and efficacy endpoints, including time-to-treatment failure (TTF), tumor response in metastatic lesions and changes in tumor markers, were investigated retrospectively using electronic medical records. The TTF of group with HFS of grade 1 and ≥2 was significantly longer than that of group with no HFS, respectively (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.18-0.87 for group with grade 1; HR, 0.42, 95% CI, 0.19-0.90 for group with grade ≥2). Significantly higher disease control rates for the liver metastasis were observed in patients with HFS (grade 1 and greater) than in those without HFS (92.9 vs. 42.9%, p=0.009). Furthermore, prevention of increases in tumor marker levels (carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3) and National Cancer Center-Stomach-439 (NCC-ST439)) was evident in patients with HFS. This study clearly showed a significant correlation between HFS and some efficacy markers of capecitabine therapy in patients with metastatic breast cancer, and suggests that early dose adjustment based on severity of HFS might improve efficacy. Studies are needed to explore predictive biomarkers for HFS/efficacy, so that capecitabine therapy can be further tailored to patient response.

Investigation of hand-foot syndrome (HFS) observed in pazopanib (P)-treated patients (pts) with renal cell carcinoma (RCC).

3061 Background: HFS is an adverse-effect of several agents used to treat cancer, particularly the VEGF TKIs. HFS can be debilitating for patients, affecting their physical, mental, and social well-being. This study sought to explore demographic, pharmacokinetic (PK) and pharmacogenetic (PGx) factors which may contribute to pazopanib-related HFS in pts with RCC. Methods: Week (wk) 4 plasma P trough concentrations (Cmin) were determined for 204 out of 225 pts with advanced RCC from a phase II study (VEG102616). Logistic and ordinal regression analyses were used to evaluate the effect of demographic (gender, race, baseline weight and height) and wk 4 Cmin on occurrence and severity of HFS, respectively. For the PGx analyses, DNA samples were collected from consenting pts with advanced RCC from three P clinical studies; VEG102616 (phase II), VEG105192 (phase III), and VEG107769. Pts were defined as HFS cases (NCI-CTCv3 grade ≥ 1, n=33) or controls (grade = 0 with treatment duration >28 days, n=321). A total of 3012 SNPs in 89 candidate genes were evaluated. The penalized maximum likelihood logistic regression was used to evaluate the effect of genotypes on the HFS case-control status. Results: While the overall incidence was low (7.7%), a high proportion of east and south-east Asians exhibited HFS (21/71, 30%) compared to Caucasians (22/489, 4%). Wk4 Cmin (P = 0.0005) and race (P = 0.03) were significantly associated with occurrence of HFS by logistic regression. A similar correlation was observed between maximal HFS grades (CTC v3) and wk4 Cmin (P < 0.0001) and race (P = 0.0045). None of the genetic markers were significantly associated with HFS after correction for multiple comparisions. Five SNPs in ABCG2, PDGFRA, GZMB and TPCN2 genes showed suggestive association with HFS at a nominal significance level P<0.01 and with a plausible genetic model. Conclusions: Both race (Asian vs. Caucasian) and wk4 P Cmin concentrations are significant predictors of HFS. Candidate gene analyses revealed that some genetic markers may be associated with P- related HFS. However, as none of the markers passed the significance level of multiple testing corrections, further evaluation in independent data sets is required to confirm or refute these findings.