Efficacy and safety of adapalene gel as a reactive treatment for cetuximab-induced skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck: A historical cohort comparison study.

INTRODUCTION: Despite the common occurrence of cetuximab (Cmab)-induced skin toxicity, management strategies are not well established. The traditional mainstay method consists of topical steroids, which, if used excessively, may give rise to other concerns. Alternatively, adapalene can activate epidermal growth factor receptor pathways to potentially alleviate these toxicities. METHODS: We prospectively studied 31 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who were eligible to use adapalene gel as a reactive treatment for topical steroid-refractory skin toxicity. For comparison, we retrospectively reviewed 99 patients with R/M SCCHN (historical control cohort) whose skin toxicity was mainly treated with topical steroids. We compared the frequency and severity of Cmab-induced skin toxicity, Cmab therapy status (e.g., dose modification), side effects caused by topical steroids and adapalene gel itself, and other medical interventions. RESULTS: Adapalene gel was used by eight patients (25.8%) in the prospective cohort. Patients in the historical control cohort more frequently required escalation of topical steroid potency (34.3% vs. 12.9%, p = 0.022). Although there was no statistically significant difference in the frequency of grade ≥3 facial skin rash and paronychia between the two cohorts, the prospective cohort showed a significantly shorter time to complete recovery from grade 2/3 paronychia (16 vs. 47 days, p = 0.017). Further, while no skin infections were observed in the prospective cohort, 13 patients in the historical control cohort developed skin infections, especially periungual infection (0% vs. 13.1%, p = 0.024). In addition, no patients in the prospective cohort received a dose reduction of Cmab due to skin toxicities, compared to 20 patients in the historical control cohort (0% vs. 20.2%, p = 0.003). No apparent adapalene gel-related side effects were observed. CONCLUSIONS: Adapalene gel may be an effective management option for topical steroid-refractory Cmab-induced skin toxicities and could improve compliance with Cmab therapy.

A pharmacist-led opioid de-escalation program after completion of chemoradiotherapy in locally advanced head and neck cancer.

Background: Persistent opioid use frequently leads to substantial negative impacts on quality of life, and as the outlook for numerous cancer types continues to improve, these complications become increasingly crucial. It is essential to acknowledge that extended or excessive opioid use may result in adverse effects in patients who completed radiation therapy (RT). Methods: In this time-series analysis, we compared the outcomes of patients who participated in the pharmacist-led opioid de-escalation (PLODE) program after completing concurrent radiotherapy (CRT) between June 2018 and February 2019 against patients who completed CRT between June 2017 and March 2018 and did not participate in the program. Results: Among 61 patients, 16 (26%) used opioids after completing CRT and participated in the PLODE program. Before starting the program, 93 patients completed CRT between June 2017 and March 2018 and 32 (34%) used opioids at CRT completion. These patients were deemed the control group. In the PLODE group, outpatient pharmacist intervention was performed, with 29 total interventions related to opioid use, of which 16 (55%) recommended tapering or discontinuing opioids according to the definition of this program. Patients who participated in the PLODE program discontinued opioids significantly earlier than those in the control group (median time to opioid discontinuation 11 days vs. 24.5 days, p < 0.001). None of the patients in the PLODE group resumed opioid use following discontinuation or escalated opioid dosing due to worsening pain. Conclusion: This study showed the utility of pharmacist-initiated interventions for opioid use in patients with head and neck cancer who had completed CRT.

A Case Series on Pain Accompanying Photoimmunotherapy for Head and Neck Cancer.

One of the most severe side effects of photoimmunotherapy (PIT) for head and neck cancer is pain. As there are presently no detailed reports on pain and pain management in PIT, we conducted a retrospective case series study. We conducted a retrospective study of five patients who had received PIT at the National Cancer Center Hospital East between January 2021 and June 2022 using medical chart data. All patients experienced pain, evidenced by an increased numerical rating scale (NRS) after PIT, regardless of the illumination method. The daily change in mean NRS rating shows that the pain was highest on the day of PIT, with ratings of 6.8 and 7.8 for the frontal and cylindrical diffuser methods, respectively; it dropped the following day quickly. Four of the five patients received fentanyl injections for postoperative pain management beginning on postoperative day (POD) 0. All patients who underwent therapy using a cylindrical diffuser required postoperative pain management with opioid drugs. Pain after PIT tended to be most intense immediately after or one hour after illumination and declined the following day, suggesting the need to have a pain relief plan in place in advance.

Impact of outpatient pharmacy interventions on management of thyroid patients receiving lenvatinib.

OBJECTIVES: Medical oncologists and pharmacists at our institution established an integrated support program aimed at preventing unnecessary treatment interruption or dose reduction during oral targeted therapy with lenvatinib. Here, we evaluated the benefits of this program in managing patients with thyroid cancer receiving lenvatinib. METHODS: We retrospectively evaluated thyroid cancer patients who received lenvatinib between May 2015 and March 2017. This descriptive study collected records in which pharmacists contributed to changing doctors' prescriptions and categorized the interventions. RESULTS: During the study period, 24 thyroid cancer patients were treated with lenvatinib. Among patients, the incidence of temporary interruption and dose reduction of lenvatinib due to adverse drug reactions was 100% (n = 24) and 83.3% (n = 20), respectively. There were 193 temporary interruptions of lenvatinib due to adverse drug reactions. A total of 501 outpatient pharmacy services were conducted by pharmacists in collaboration with oncologists, of which 125 were interventions (24.9%). In addition, pharmacists conducted 156 telephone follow-up services; 18 (11.5%) of these were to consult an oncologist about a patient's confirmed problems and resulted in the decision to continue observation with no medical intervention while 41 (26.2%) resulted in the oncologist deciding to temporarily interrupt lenvatinib treatment after the report of an adverse drug reaction from the pharmacist. CONCLUSION: Pharmacist interventions in collaboration with medical oncologists improved lenvatinib therapy. Interventions for outpatients were conducted not only in outpatient clinics but also by telephone follow-up, clarifying the importance of continuous management for patients at risk of adverse reactions and misuse of oral medicine.

Electric-field penetration depth and dielectric spectroscopy observations of human skin.

BACKGROUND: The dynamic behavior of water molecules remains an important subject for understanding human skin. The change in the dynamics of water molecules from those in bulk water can be effectively observed by dielectric spectroscopy. To study water in the human skin in vivo, non-invasive and non-destructive measurements are essential. Since many unknowns remain from previous research, in this report we employ a two-layer dielectric model to evaluate the penetration depth of the electric field and use the results in measurements on human skin. MATERIALS AND METHODS: We used open-ended coaxial probes with different diameters to perform time-domain reflectometry (TDR) measurements for an acetone-Teflon double-layer model and for human skin from various parts of the body. RESULTS: The electric-field penetration depth obtained from model measurements increases with the increasing outer diameter of open-ended coaxial electrodes. For skin measurements, the relaxation strength corresponding to the water content shows a clear dependence on the epidermal thickness of the measured body parts. CONCLUSION: We determined the depth distribution of the water content of skin from results of dielectric measurements obtained using electrodes with various electric-field penetration depths. We found exponential decays with the thickness of the epidermis of each body part for several examinees. This study suggests an effective method for detailed evaluations of human skin.

Impact of pharmacy collaborating services in an outpatient clinic on improving adverse drug reactions in outpatient cancer chemotherapy.

BACKGROUND: Collaboration between pharmacists, doctors, and nurses in outpatient treatment is beneficial; however, such services are limited in Japan due to the lack of a healthcare reimbursement fee for outpatient pharmacy services at outpatient clinic. OBJECTIVE: We evaluated the impact of a service in which clinical pharmacists collaborated with an oncologist at an outpatient clinic in the treatment of adverse drug reactions in outpatient cancer chemotherapy. METHODS: We performed a retrospective cohort study using patients' medical records and treatment diaries. Subjects were patients who received outpatient chemotherapy via a clinical pharmacist collaboration service provided by six outpatient pharmacists and an oncologist at an outpatient clinic between June and August 2016. RESULTS: During the study period, the total number of outpatient services was 2508, with 2055 (81%) related to chemotherapy. The six outpatient pharmacists provided interventions to 498 of the 2055 cases (24%). Of the 498 interventions, 103 (20%), in addition to oncologist's prescription, were suggested treatments for adverse drug reactions due to cancer chemotherapy. Oncologists approved a total of 82 prescription suggestions from pharmacists (79%) to 63 patients. Fifty-seven percent (n = 47) of the adverse drug reactions were improved following the pharmacists' suggested prescriptions. CONCLUSIONS: This is the first study to clarify the benefits of outpatient pharmacy services in which pharmacists collaborate with oncologists at an outpatient clinic for the management of adverse drug reactions in cancer patients in Japan.

Predictive Value of Cetuximab-Induced Skin Toxicity in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and NECK.

Background: Skin toxicity is a common adverse event during cetuximab (Cmab) treatment. However, few reports have investigated the correlation between skin toxicity and the efficacy of Cmab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Methods: We retrospectively reviewed 112 R/M SCCHN patients who received palliative chemotherapy with Cmab. Main eligibility criteria included primary disease in the oral cavity, hypopharynx, nasopharynx, oropharynx, or larynx; no prior history of EGFR-directed therapy; receipt of Cmab plus chemotherapy as first-line therapy for recurrent or metastatic disease; and follow-up for more than 90 days. We analyzed the time to first occurrence and time of maximum grade skin toxicity, and its predictive value with regard to treatment efficacy. Results: After a median follow-up of 393 days (range 109-1501 days), 105 (94%) and 20 (18%) patients had skin toxicity of any grade and grade 3, respectively. Among them, 8 patients with grade 3 acneiform rash, skin rash, or paronychia within 90 days after treatment initiation ("early skin toxicity") had improved progression-free survival (PFS) (log-rank test, P = 0.045; 2-year PFS, 25.0 vs. 2.9%) and overall survival (OS) (log-rank test, P = 0.023, 2-year OS, 50.0 vs. 14.4%) compared with those with < grade 3 toxicity. A greater proportion of patients with early skin toxicity than patients without this toxicity could proceed with Cmab maintenance (88 vs. 44%, P = 0.021). Multivariate analysis identified early skin toxicity as an independent predictor of better PFS (hazard ratio [HR] = 0.363, 95% confidence interval [CI] 0.142-0.924, P = 0.034) and OS (HR = 0.187, 95% CI: 0.045-0.781, P = 0.022). Conclusion: Grade 3 Cmab-induced skin toxicity within 90 days was associated with better survival in R/M SCCHN. Effective rash management therefore seems necessary to realize the benefit of Cmab treatment.