Managing the Adverse Events Associated with Pembrolizumab and Lenvatinib Therapy in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynaecological cancer. The combination of lenvatinib and pembrolizumab has exhibited efficacy as the second line treatment for advanced EC, with a significant benefit in terms of progression free survival (PFS) and overall survival, but the adverse events (AE) profile is complex. AEs associated with the treatment may represent a limitation to this combination. Here, we report the case of a 38-year-old female patient diagnosed with stage IV EC elsewhere, whose disease progressed after the first line of treatment and was referred to a specialised cacncer centre in Muscat, Oman, in 2021. We treated her with the combination of lenvatinib and pembrolizumab. During the course of the treatment, she developed hand-foot syndrome grade III and hypothyroidism grade II. The AEs were managed with supportive medications, dose interruptions, dose reductions and multidisciplinary care, which allowed the continuation of the treatment. The patient achieved a good partial response and an ongoing PFS of more than 12 months.

Hand-foot syndrome in cancer patients on capecitabine: examining prevalence, impacts, and associated risk factors at a cancer centre in Malaysia.

INTRODUCTION: Hand-foot syndrome (HFS) significantly impacts quality of life in cancer patients undergoing capecitabine treatment. This study assessed capecitabine-associated HFS prevalence, its impacts on chemotherapy treatment, and identified risk factors in multiracial Malaysian patients. METHODS: We included adult cancer patients receiving capecitabine at Sarawak General Hospital for at least two cycles from April 1, 2021 to June 30, 2022. HFS rates, time to HFS, and proportions of HFS-related treatment modifications were determined. Characteristics between patients with and without HFS were compared and multivariable logistic regression was used to identify risk factors for all-grade HFS and grade ≥2. RESULTS: Among 369 patients, 185 (50.1%) developed HFS, with 14.6% experiencing grade ≥2 and 21.6% (40/185) underwent treatment modifications. Risk factors for all-grade HFS include older age (OR 1.03 95%CI 1.01, 1.06), prior chemotherapy (OR 2.09 95%CI 1.22, 3.58), higher capecitabine dose (OR 2.96 95%CI 1.62, 5.38), prolonged treatment (OR 1.36 95%CI 1.21, 1.51), folic acid intake (OR 3.27 95%CI 1.45, 7.35) and lower neutrophil count (OR 0.77 95%CI 0.66, 0.89). For HFS grade ≥2, older age (OR 1.04 95%CI 1.01, 1.08), female sex (OR 2.10 95%CI 1.05, 4.18), Chinese race (OR 2.10 95%CI 1.06, 4.18), and higher capecitabine dose (OR 2.62 95%CI 1.28, 5.35) are significant risk factors. Use of calcium channel blockers were associated with reduced risks of all-grade HFS (OR 0.27, 95%CI 0.12, 0.60) and grade ≥2 (OR 0.21 95%CI 0.06, 0.78). CONCLUSION: This study provides real-world data on capecitabine-induced HFS in Malaysian patients and identifies risk factors that may offer insights into its understanding and management.

A novel animal model of tegafur-induced hand-foot syndrome.

Hand-foot syndrome (HFS) is a common side effect of fluoropyrimidine anticancer drugs and often becomes a dose-limiting manifestation of toxicity once it occurs. The precise mechanism of HFS remains unclear, and effective measures to prevent or relieve it are currently limited. To investigate the pathogenesis of HFS and effective measures for treating or preventing it, establishment of animal models is crucial. Here, we gave male SD rats 170 mg/kg of tegafur (prodrug of 5-FU) daily for 35 days and evaluated their clinical and histopathological characteristics and pain-related behavioral tests. TUNEL-positive apoptotic cells and 5-FU concentrations in the plantar skin were also evaluated to investigate the mode of toxicity. Tegafur treatment induced hypersensitivity to mechanical pressure on the plantar surface beginning in Week 3, with decreased locomotor activity. Focal desquamation of the plantar skin was observed almost concomitantly and gradually worsened to palmar and plantar skin thickening with severe desquamation, cracks, or both. Histopathological lesions in the plantar skin at treatment end included desquamation and thickening, with epidermal cell swelling and spongiosis and focal inflammation in the dermis. The time-course of development and the characteristics of the tegafur-induced skin lesions were highly similar to those in human fluoropyrimidine-induced HFS, indicating that a HFS rat model was successfully established. Localized high concentrations of 5-FU in the palmar and plantar skin, with increased apoptosis, are likely involved in the mode of toxicity. Our model should clarify the pathogenesis of HFS, providing new insights into the best supportive care and prevention.

[Cutaneous adverse events to systemic anticancer therapies : Hand-foot syndrome and nail changes]. / Kutane Nebenwirkungen onkologischer Systemtherapien : Hand-Fuß-Syndrom und Nagelveränderungen.

BACKGROUND: Hand-foot syndrome (HFS) and nail changes are frequent adverse events of anticancer therapies. OBJECTIVES: To provide a review of current evidence in HFS and nail disorders associated with medical tumor treatment. MATERIALS AND METHODS: Basis is the current German S3 guideline "Supportive therapy in oncologic patients" and literature on this topic published since the guideline was finalized. RESULTS: Two variants of HFS are distinguished: a chemotherapy-associated and a kinase-inhibitor-associated variant. In the first form, painful erythema, blisters and ulceration can occur, also in other areas with a high number of sweat glands such as axillary and inguinal regions. Thus, the secretion of toxic substances through sweat glands is a proposed pathogenetic mechanism. For the second form, which results in callus-like painful thickening of the horny layer on areas of mechanic pressure, a vascular mechanism is proposed. For prophylaxis of HFS, avoidance of mechanical stress, regular cleaning of predisposed areas, and also urea- and diclofenac-containing ointments are recommended; in case of infusions (taxanes, doxorubicine), cooling of hands and feet during infusion is recommended. In case of manifest HFS, dose reduction or prolongation of intervals of the associated treatment are recommended. Nail changes often develop under therapy with chemotherapeutic agents but also under treatment with agents such as checkpoint inhibitors or under targeted therapy. Different components of the nail unit may be involved such as the nail matrix, nail bed, nail plate, hyponychium, lunula and proximal and lateral nail folds. CONCLUSION: This work gives insight into the pathophysiology of HFS and nail disorders that develop under systemic oncologic treatments and gives recommendations for prophylaxis and treatment.

A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer.

BACKGROUND: Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer. METHODS: Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25. RESULTS: Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks. CONCLUSIONS: The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT02393755.

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

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

A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Effect of Topical Urea for Secondary Prophylaxis of Hand Foot Skin Reaction in Renal Cell Cancer Patients on Sunitinib Therapy.

INTRODUCTION: Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. OBJECTIVE: In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. METHODS: Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. RESULTS: The results showed that urea-based cream was not superior to placebo (P = .075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. CONCLUSION: The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib.

Relationship between hand-foot skin reaction and external force on patients with hepatocellular carcinoma: A cohort study.

PURPOSE: Hand-foot skin reaction (HFSR), a side effect of tyrosine kinase inhibitor (TKI) treatment, makes it difficult to walk and perform daily activities because of pain in the limbs. HFSR occurs predominantly in the sites where external forces (pressure and shear stress) are applied. This study aimed to determine whether pressure or shear stress induces the occurrence of HFSR. METHODS: This cohort study was conducted in patients who received TKI treatment for hepatocellular carcinoma. The external forces applied to the sole of the patients' foot while walking was measured, and its association with the occurrence of HFSR was examined. The degree of HFSR was assessed by the patient's response during the examination and by photographs of their feet. The patients' feet were divided into low (grade <2) or high (grade ≥2) HFSR foot group, and the differences in external forces between the groups were analyzed using t-test and Cox hazard analysis. RESULTS: Analysis of the feet of 55 study participants (n = 110) showed no significant difference between the groups on t-test (p ≥ 0.05), however, Cox hazard analysis showed an increased risk of HFSR with higher peak shear stress values at the fifth metatarsal head (hazard ratio = 1.01, p = 0.047; 95% confidence interval = 1.00-1.02). CONCLUSION: Shear stress is possibly related to HFSR occurrence. Nurses should assess whether patients' shoes fit their feet before initiating TKI treatment. They should instruct patients to wear shoes that are fit of both diameter and width for their feet.

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

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

TXB-001, a newly-developed polymer-conjugated anthracycline: Significantly lower adverse effects in animal models of alopecia and hand-foot syndrome.

Anthracycline anti-cancer drugs have been widely used in the treatment of several cancers; however, their use is limited by adverse effects (AEs). Alopecia is a common AE that is minimally invasive, but adversely affects mental health and reduces quality of life (QoL). Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL, a liposomal formulation of doxorubicin (DOX). Although it is not a life-threatening condition, HFS affects function and reduces QoL. TXB-001 is a new candidate polymer-conjugated anthracycline anti-cancer drug, and modified and optimized polymerized pirarubicin (THP), known as P-THP, is expected to have low toxicity and high efficacy. The anti-cancer effects of TXB-001 were examined using the 4T1 mouse model. An alopecia mouse model and HFS rat model were used to evaluate the alopecia- and HFS-inducing effects of TXB-001 and compare their severity with existing anthracycline anti-cancer drugs. A pharmacokinetic analysis of plasma as well as chest, palmar, and plantar skin samples after the single intravenous administration of DOXIL and TXB-001 to rats was also performed. The results obtained revealed that TXB-001 exerted similar anti-cancer effects to those of DOXIL in mice, weaker alopecia-inducing effects than DOX, DOXIL, and THP in mice, and no or markedly weaker HFS-like changes than DOXIL, which induced significant histopathological changes. The results of the pharmacokinetic analysis showed the accumulation of DOXIL, but not TXB-001, in skin, particularly palmar and plantar skin samples, and these differences were considered to contribute to their HFS-inducing effects.

Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial.

PURPOSE: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS. METHODS: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression. RESULTS: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4). CONCLUSION: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

Chemotherapeutic metabolism presenting as a recalcitrant case of hand-foot syndrome and mucositis.

INTRODUCTION: Mercaptopurine (6MP) and methotrexate (MTX) are commonly used for maintenance chemotherapy for acute lymphoblastic leukemia (ALL). These medications have been associated with various side effects such as myelosuppression, colitis, and thyroiditis in addition to numerous cutaneous adverse events. Cutaneous side-effects most reported include mucositis, alopecia, xerosis, and pruritus. We report an interesting case of hand-foot syndrome to 6MP in a child on maintenance therapy for B-cell ALL from an alteration in medication metabolism. CASE: We report a 10-year-old male on maintenance chemotherapy for pre-Bcell ALL who presented to the hospital with worsening oral lesions and erythematous, fissured plaques on the palms and soles. Maintenance therapy consisted of IV vincristine and 5-day pulse of steroids every 12 weeks, daily 6MP, and weekly MTX, which were increased to ≥ 150% of standard dosing due to persistent absolute neutrophil counts > 1500. Metabolites obtained on admission demonstrated elevated 6MMP metabolites at 35,761 (normal < 5700). TPMT and NUDT15 enzyme activity were normal and no alterations in genotyping were discovered. OUTCOME: Patient's oral chemotherapy, including both 6MP and MTX, were stopped and allopurinol 100 mg daily was initiated, which lead to overall improvement. DISCUSSION: Clinical findings of acute mucositis and worsening of hand-foot syndrome, in the setting of inadequate myelosuppression in a child on maintenance therapy for ALL should raise concerns to consider altered metabolism pathway leading to toxic metabolite buildup. Allopurinol can play in improving cutaneous manifestation and chemotherapeutic dosing in patients with altered metabolism.

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

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

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

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

Paclitaxel-induced dorsal hand-foot syndrome.

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

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

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

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

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

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

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

Capecitabine and Hand-foot Syndrome: A Case Report.

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