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 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.

Paclitaxel Plus Cetuximab as 1st Line Chemotherapy in Platinum-Based Chemoradiotherapy-Refractory Patients With Squamous Cell Carcinoma of the Head and Neck.

Purpose: We sought to evaluate the efficacy and safety of the combination of cetuximab (Cmab) and paclitaxel (PTX) in patients with squamous cell carcinoma of the head and neck (SCCHN) who had unresectable recurrent or metastatic (R/M) disease after platinum-based chemoradiotherapy. Materials and Methods: Data on 23 patients with SCCHN who received paclitaxel and cetuximab (Cmab) for R/M disease no more than 6 months after CRT completion were retrospectively reviewed. PTX and Cmab were given in a 28-day cycle (PTX, 80 mg/m2 on days 1, 8, and 15; Cmab, loading dose 400 mg/m2 followed by a weekly 250 mg/m2). The differences in prognosis between subgroups in different clinical settings were also assessed. Results: CRT had been delivered as definitive treatment in 13 cases (57%) and as adjuvant treatment in 10 (43%). Median time from CRT completion to disease recurrence or metastasis was 73 days (1-152). The best objective response and disease control rates were 52 and 83%, respectively, with 12 partial responses and seven cases of stable disease by Response Evaluation Criteria in Solid Tumors (RECIST). A total of 17 of 23 patients (74%) achieved a degree of tumor shrinkage. Median progression-free survival (PFS) and overall survival (OS) were 7.0 (95% confidence interval [CI]: 3.7-8.4) and 16.3 months (95% CI: 7.8-23.3), respectively. Patients with a longer duration (≥60 d) from CRT completion to disease progression had a statistically significantly longer OS than the others (median OS 22.3 vs. 8.1 months, log-rank test; p = 0.034). Main Grade 3 toxicities included neutropenia (13%), anemia (13%), and hypomagnesemia (13%). No Grade 4 toxicity or treatment-related death was seen. Conclusion: PTX and Cmab is a tolerable and effective option in SCCHN patients with symptomatic CRT-refractory disease. Its favorable effects on tumor shrinkage will help relieve tumor-associated symptoms.

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.

Gemcitabine monotherapy in patients with heavily treated nasopharyngeal cancer: a case series.

BACKGROUND: Although gemcitabine is thought to play a critical role in the treatment of nasopharyngeal cancer, no research to evaluate the efficacy and toxicity of gemcitabine monotherapy has been conducted in Japan. METHODS: We retrospectively reviewed eight nasopharyngeal carcinoma patients treated with gemcitabine monotherapy at National Cancer Center Hospital East between May 2015 and August 2016. The main eligibility criteria were (1) histopathologically proven NPC; (2) tumor recurrence or an initial M1 TNM stage diagnosis; (3) at least two other types of systemic chemotherapy prior to gemcitabine; (4) no other active malignant tumor during treatment. RESULTS: All patients were administered gemcitabine 800-1000 mg/m2 on days 1, 8, and 15, repeated every 4 weeks. Gemcitabine was given as third-line systemic chemotherapy in six (74%) patients, as fourth-line in one (13%) and as fifth-line in one (13%). One patient had a complete response and one had a partial response, giving an overall response rate of 25%; four patients (50%) had stable disease and two (25%) experienced disease progression. The main toxicity was myelosuppression, with grade 3 leukopenia in three (38%) patients and neutropenia in four (50%). There were no treatment-related deaths. Median dose intensity and relative dose intensity of gemcitabine were 620 mg/m2/week and 97.5%, respectively. CONCLUSION: Our findings suggest that GEM monotherapy is well tolerated and has potential as an active agent in Japanese patients with recurrent/metastatic NPC who have been heavily pretreated.