[Retrospective Analysis of the Afatinib Clinical Pathway during the 28-Day Introductory Period-The Japanese Style of Collaborative Drug Therapy Management(J-CDTM)].

Afatinib is a newly approved second-generation epidermal growth factor receptor-tyrosine kinase inhibito r(EGFR-TKI). Afatinib has been shown to prolongthe overall survival of patients with non-small cell lungcancer (NSCLC) with EGFR mutations compared with the standard chemotherapy. However, Grade 3 or 4 toxicities, includingdiarrhea, rash, paronychia, and stomatitis, have been observed more frequently in patients treated with afatinib than in those treated with first-generation EGFR-TKIs. Accordingly, our institution developed an afatinib clinical pathway (the afatinib pathway), which was designed by certified nurses, medical physicians, and certified pharmacists, with the goal of reducing the severity of diarrhea and rash that occur most frequently duringthe 28-day introductory period of afatinib treatment. Between May and October 2014, afatinib was administered accordingto the afatinib pathway to 14 patients with NSCLC and EGFR mutations. Of these patients, only one (7.1%) experienced Grade 3 diarrhea. No other patient experienced Grade 3 or 4 toxicity. The afatinib pathway was effective in reducingthe severities of the diarrhea and rash duringthe 28-day introductory period of the afatinib treatment. Our implementation of the afatinib pathway could be considered the Japanese style of collaborative drugtherapy management (J-CDTM).

[Denosumab for bone metastasis of thoracic tumors-preparation of a practice manual and evaluation of its effectiveness].

The anti-receptor activator of nuclear factor-kB ligand (RANKL) antibody denosumab is thought to be useful in the improvement of the quality of life of patients with bone metastasis from thoracic tumors, given the ease of its subcutaneous administration. However, attention has to paid to the onset of hypocalcemia when determining the optimal dosage, especially since data and methods on its prevention are limited. Our project team monitored serum calcium levels in patients receiving denosumab treatment, evaluated methods to supplement calcium and vitamin D in cases of hypocalcemia, and developed an evidence-based common manual. Subsequently, denosumab administration and hypocalcemia were evaluated as per the manual. Grade 3 hypocalcemia was observed in 2 cases before the preparation, with no new cases seen since adopting the new protocol in the manual. We conclude that the development of severe hypocalcemia associated with denosumab treatment can be avoided by prompt management of this condition in the early stages and by adopting measures listed in the practice manual.

Extracellular Water-to-total Body Water Ratio as an Objective Biomarker for Frailty in Lung Cancer Patients.

BACKGROUND/AIM: Our previous study revealed the association between extracellular water-to-total body water ratio (ECW/TBW) and the therapeutic durability of chemotherapy and/or immune checkpoint inhibitors in advanced lung cancer. We retrospectively examined the usefulness of ECW/TBW in detecting frailty compared to other bioelectrical impedance (BIA) parameters in a larger number of patients. PATIENTS AND METHODS: Lung cancer patients underwent BIA before anti-cancer therapy at our hospital between June 1, 2018 and July 31, 2020. RESULTS: Of 99 patients, 26 were assigned to ECW/TBW≥0.4 (higher group: HG) and 57 to ECW/TBW<0.4 (lower group: LG). ECW/TBW increased significantly with performance deterioration and ageing. HG patients had significantly shorter time-to-treatment failure (TTF) than LG patients. In patients with performance status 0-1, those in the HG had shorter TTF than those in the LG. ECW/TBW was the only independent predictor of TTF according to multivariate analysis. CONCLUSION: ECW/TBW is an objective biomarker for detecting frailty among lung cancer patients.

Skin Rash Can Be a Useful Marker for Afatinib Efficacy.

BACKGROUND/AIM: Although afatinib has a strong efficacy, it can be toxic; hence, we aimed to determine markers of response to afatinib in order to assess prognosis. PATIENTS AND METHODS: Information on clinical background, therapeutic effects, and adverse events was collected retrospectively at one Institution from patients treated with afatinib as initial epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). We examined the relationship between different adverse events and their effects on prognosis. RESULTS: Afatinib was used in 32 patients as the initial EGFR-TKI. Adverse events of grade 3 or higher including diarrhoea (12.5%), paronychia (6.3%), and stomatitis (3.1%) were experienced by patients. The median progression-free survival (PFS) was 15.4 months. A relationship between skin rash severity and PFS was observed. CONCLUSION: Grade 2 or higher skin rash might be a marker for long-term efficacy of afatinib when administered as a first-line treatment.

Mandatory dexamethasone strictly monitored by pharmacists reduces the severity of pemetrexed-induced skin rash.

OBJECTIVE: The present study aimed to retrospectively examine the effectiveness of mandatory dexamethasone (m-DEX) strictly monitored by pharmacists collaborating with medical physicians and nurses for reducing pemetrexed (PEM)-induced skin rash in patients with non-squamous non-small-cell lung cancer (ns-NSCLC). METHODS: We compared the rash grades during the first cycle of PEM-containing regimens between patients who received m-DEX after February 2012 and those who received dexamethasone (DEX) at their physician's discretion (d-DEX) before January 2012. RESULTS: Of 163 patients with ns-NSCLC included in this study, 89 received d-DEX and 74 received m-DEX. The mean DEX doses the night before and the day after PEM administration were significantly higher in the m-DEX group than in the d-DEX group. The frequency of grade ≥2 skin rash was significantly lower in the m-DEX group than in the d-DEX group. CONCLUSIONS: The use of m-DEX strictly monitored by pharmacists might significantly reduce the severity of PEM-induced skin rash.