Tyrosine kinase inhibitor nilotinib induced palmoplantar erythrodysesthesia: A rare case

Introduction Nilotinib is a second generation Tyrosine Kinase inhibitor (TKI) used in the treatment of Chronic Myeloid Leukemia (CML). The development of tyrosine kinase inhibitors has transformed chronic phase chronic myeloid leukemia from a disease with a poor prognosis to a treatable chronic disease. Long-term treatment with tyrosine kinase inhibitors means that patients must be clinically managed and monitored for years. While under Nilotinib tretament, the development of palmoplantar erythrodyesthesia is a very rare condition compared to other oncological drugs. Case report A 66-year-old male patient, who was diagnosed with chronic phase CML in 2019 had been placed under imatinib treatment . He had major molecular response loss in 2021, and was started on second generation TKI nilotinib 2 × 400mg/day, considering his comorbidities. We present a case of a 66-year-old patient with CML who developed palmoplantar erythrodysesthesia on the 21st day starting nilotinib treatment. Conclusion It is important to manage the side effects that develop in long-term treatments. Adverse events can have a negative impact on patient compliance and quality of life and lead to poor clinical outcomes Our case is the first to develop PPE after beginning nilotinib use. We present this phenomenon to raise awareness and ignite a review of management strategies.In this case, we wanted to emphasize the importance of managing side effects.

Moist Exposed Burn Ointment Effectiveness for Capecitabine Associated Grade II and III Hand Foot Syndrome on Stage III Colonic

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.

Safety and Tolerability of BRAF Inhibitor and BRAF Inhibitor-Based Combination Therapy in Chinese Patients With Advanced Melanoma: A Real World Study

The toxicity spectrum between Chinese and Caucasian patients with melanoma who were treated with BRAF inhibitors (BRAFi) may differ. The purpose of the present study was to assess the safety and tolerability of BRAFi and BRAFi-based combination therapies [MEK inhibitors (MEKi) or anti-programmed death-1 (PD-1) antibody] in Chinese patients with BRAF V600E/K mutation-positive metastatic melanoma. We also investigated whether treatment-related adverse events (AEs) correlated with the prognosis. This retrospective study collected data from 43 patients with BRAF V600E/K mutation-positive metastatic melanoma from a single Chinese cancer center. Of the 43 patients, 12 patients received BRAFi monotherapy, 12 patients received BRAFi+MEKi, and 19 patients received BRAFi combined with the anti-PD-1 antibody. The median follow-up time was 19 months. In the BRAFi group, the most common AEs were rashes, palmoplantar erythrodysesthesia, and arthralgia. Four out of 12 (30%) patients experienced grade 3–4 treatment-related AEs. All grades of AEs in the BRAFi+MEKi group were similar to the BRAFi group, except for higher pyrexia (58.3%) and fewer cutaneous AEs. Three out of 12 (25%) patients experienced grade 3–4 AEs, especially pyrexia (16.7%). In the BRAFi+anti-PD-1 antibody group, AEs were similar to the BRAFi group, except for an increased aminotransferase level (36.8%), increased bilirubin (31.6%), and hypothyroidism (15.8%). Eleven out of 19 (57.9%) patients experienced grade 3–4 AEs and four out of 19 (21%) patients discontinued the therapy due to AEs. Treatment-related hepatotoxicity (trHE), defined as an increase in either alanine aminotransferase (ALT), aspartate transaminase (AST), or bilirubin levels, was the only AE identified as a significant poor-prognosis indicator in this study. The median progression-free survival of patients with trHE (41.9%) was 8 months, whereas it was 18 months for those without trHE [p = 0.046, hazard ratio (HR) = 2.116]. Moreover, this association was independent of medication regimens (p = 0.014, HR = 2.971). The overall response rate of patients with trHE was significantly lower than those without trHE (44.4 vs. 60.0%, p = 0.024), and we observed a similar trend in patients treated with BRAFi, BRAFi+MEKi, and BRAFi+anti-PD-1 antibody. In conclusion, BRAFi and BRAFi-based combination therapies were tolerable with reversible AEs in Chinese patients with melanoma. The trHE in patients receiving BRAFi and BRAFi-based regimens might indicate a poor therapy-related prognosis.

Analysis of first-line treatment in older patients with metastasic colorectal cancer

Objective The purpose of this study was to analyse the effectiveness and safety of first-line treatment of metastatic colorectal cancer (CRCm) in older patients treated in a tertiary hospital. Material and methods This was an observational and retrospective study, including patients aged 75 years or older, with CRCm, who received chemotherapy treatment in 2017. The main variables studied were type of treatment, Progression-Free Survival (PFS), Overall Survival (OS), dose reductions, and treatment delays due to adverse events. Results A total of 59 patients (71.2% men) with a median age of 76 years were enrolled in this study. About 70% presented colon cancer, with the left colon being the most frequent location. They were treated with 9 different schemes, in most cases using polychemotherapy and biological agents. The median PFS and OS was 12 and 30 months, respectively. A total of 23/59 of patients started treatment at doses lower than recommended in the clinical practice guidelines. In terms of safety, 34/59 of patients had at least one dose reduction, and 30/59 suffered one treatment delay. The most frequent adverse reactions were asthenia, peripheral neuropathy, diarrhoea, and palmoplantar erythrodysesthesia. Conclusion Our patients presented baseline clinical characteristics similar to the general adult population, with no tumour characteristics associated with advanced age. The efficacy and toxicity were similar to those in the clinical trials, although our patients had more dose reductions. Considering the heterogeneity of patients and in the absence of clinical trials in the older population, real-life studies can be very useful.

Hyperproliferative keratinocytic cutaneous adverse events and inflammatory palmoplantar erythrodysesthesia in melanoma patients treated with encorafenib compared to other BRAF inhibitors.

9590 Background: BRAF inhibitor (BRAFi) an MEK inhibitor (MEKi) monotherapies have shown to cause more cutaneous adverse events (cuAEs) in monotherapy compared to combination therapy. Encorafenib in combination with binimetinib showed improved PFS in patients with BRAF mutant melanoma (14.9 months). Furthermore, encorafenib showed superiority over vemurafenib. Objective: The aim of this study was to investigate cuAEs of melanoma patients treated with encorafenib and/or binimetinib and compare them to other BRAFi and MEKi induced cuAEs reported in the literature and observed in our control population. Methods: Patients treated with encorafenib, binimetinib, and other BRAFi/MEKi within approved clinical trials at the University Hospital of Zurich were collected and analyzed. Clinical and histological assessments were performed. Results: In 111 patients treated with BRAFi and/or MEKi, 212 related or possibly related cuAEs were identified. The percentage of patients with at least one cuAE is shown in the table below. The most frequent cuAEs observed in patients treated with encorafenib where palmoplantar hyperkeratosis (PPH, 50%), palmoplantar erythrodysesthesia (PPD, 53.8%) and alopecia (42.3%), whereas acanthopapillomas (83%), maculopapular exanthemas (63.3%), PPH and PPD (each 50%) prevailed in patients treated with vemurafenib. The most frequent observed cuAE in patients with dabrafenib/trametinib combination therapy were maculopapular exanthemas (18.2%) and erythema-annulare-like eruptions (18.2%), with encorafenib/binimetinib combination therapy PPH (10.6%) respectivly. Conclusions: Encorafenib showed less hyperproliferative cuAEs as previous BRAFi. However, PPH and PPD seem to occur more often compared to the literature of other BRAFi. Both is supporting the argument that encorafenib is a second generation BRAFi with a longer dissociation time. [Table: see text]