Osamu Kanai

Repetitive responses to nanoparticle albumin-bound paclitaxel and carboplatin in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare tumor with a poor prognosis. Although cisplatin plus pemetrexed is the standard chemotherapy for patients with unresectable MPM, few agents are available for MPM patients who do not tolerate pemetrexed. Here, we report the first case of an MPM patient for whom the combination of nanoparticle albumin‐bound paclitaxel and carboplatin (nabPC) repetitively achieved tumor regression. A 76‐year‐old man was diagnosed with epithelioid MPM. One cycle of carboplatin plus pemetrexed and two cycles of gemcitabine were administered but failed to inhibit tumor progression. By contrast, four cycles of nabPC resulted in a good response. Upon disease progression, four cycles of nabPC were performed again and resulted in a modest response. In conclusion, based on the present case, nabPC is a potential alternative chemotherapeutic agent for MPM, especially for MPM patients who do not tolerate pemetrexed.

Small cell lung cancer transformation during immunotherapy with nivolumab: A case report

We report a rare case of transformation of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC), without epidermal growth factor receptor (EGFR) gene mutation, during immunotherapy treatment with nivolumab. A 75-year-old man was referred to our hospital following the observation of a 64 mm mass in a chest computed tomography (CT) scan. A transbronchial biopsy of the mass identified the pathological presence of poorly differentiated NSCLC, with no histological signs of SCLC. No mutations were identified in the EGFR gene. A clinical diagnosis of NSCLC (cT3N3M1a, stage IV) was made following a positron emission tomography (PET)–CT scan and enhanced brain magnetic resonance imaging. Docetaxel and bevacizumab were selected as the first-line chemotherapy regimen; however, after two cycles, the patient developed a gastrointestinal perforation, and discontinuation of cytotoxic chemotherapy was recommended. Owing to gradual disease progression, immunotherapy with nivolumab was selected as the second-line regimen. During the immunotherapy, the tumor continued to progress and some subcutaneous tumors emerged. Biopsy of a subcutaneous tumor revealed SCLC, with positive immunostaining for cluster of differentiation 56, synaptophysin, and thyroid transcription factor-1. Serum tumor markers of SCLC were also elevated. Based on these results, we concluded that in this case NSCLC had transformed to SCLC during immunotherapy with nivolumab.

Retreatment with pembrolizumab in advanced non-small cell lung cancer patients previously treated with nivolumab: emerging reports of 12 cases

PurposeAfter approval of anti-programmed cell death (PD)-1 antibodies, treatment for non-small cell lung cancer (NSCLC) has drastically changed. However, even in patients with favorable effects, therapeutic efficacy does not last long. Recently, retreatment with anti-PD-1 antibody has received attention. The aim of this study was to evaluate the efficacy and safety of retreatment with pembrolizumab in NSCLC patients previously treated with nivolumab.Patients and methodsWe retrospectively reviewed NSCLC patients retreated with pembrolizumab who were previously treated with nivolumab. We collected the following data: patient characteristics, number of cycles of nivolumab and pembrolizumab, treatment interval between nivolumab and pembrolizumab, best response, and immune-related adverse events.ResultsTwelve patients were reviewed. The median number of cycles of nivolumab was 12.5 (range 2–32 cycles). Seven patients (58.3%) achieved a partial response (PR) and two patients (16.7%) achieved stable disease (SD). Eight patients (66.7%) received cytotoxic chemotherapy between nivolumab and pembrolizumab. The median number of cycles of chemotherapy treatment was 4 (range 1–9 cycles). The median number of cycles of pembrolizumab was 3.5 (range 1–17 cycles). One patient (8.3%) achieved PR and four patients (33.3%) achieved SD as their best response to pembrolizumab. All patients showing response to pembrolizumab had very high (≥ 80%) tumor PD-Ligand 1 expression.ConclusionsThis study suggested that retreatment with anti-PD-1 antibody is a reasonable option for selected NSCLC patients.

Concurrence of nivolumab-induced interstitial lung disease and cancer invasion

Nivolumab improves overall survival rates of patients with advanced or recurrent non‐small‐cell lung cancer (NSCLC). Among immune‐related adverse events caused by nivolumab, interstitial lung disease (ILD) is a clinically serious and potentially life‐threatening toxicity, for which appropriate treatment is needed immediately. However, ILD is sometimes difficult to distinguish from invasive lung adenocarcinoma using only computed tomography (CT) findings. A 71‐year‐old man was diagnosed with advanced lung adenocarcinoma. The patient developed dyspnoea after eight cycles of nivolumab, when chest CT indicated ILD classified with a cryptogenic organizing pneumonia (COP) pattern. Although immunosuppressive therapies improved the CT findings temporarily, dyspnoea was re‐exacerbated 2 months later. The CT findings helped in making the diagnosis of a combination of ILD and invasive lung cancer, confirmed by a transbronchial lung biopsy. In conclusion, nivolumab‐related ILD and cancer invasion may concur and aggressive biopsy should be considered if nivolumab‐related ILD is refractory to immunosuppressive therapy.

Nasogastric tube‐administered alectinib achieved long‐term survival in a crizotinib‐refractory nonsmall cell lung cancer patient with a poor performance status

Alectinib shows remarkable efficacy against anaplastic lymphoma kinase (ALK)‐positive nonsmall cell lung cancer (NSCLC), with minimal adverse effects. Therefore, alectinib may provide a survival benefit to ALK‐positive NSCLC patients with a poor performance status. If the medication cannot be taken by mouth, the patient may be given alectinib through a nasogastric tube.

Efficacy and safety of nivolumab in non-small cell lung cancer with preexisting interstitial lung disease: Nivolumab in patients with ILD

The risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non‐small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI‐related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD.

Cutaneous lymphangitis carcinomatosa made cervicofacial oedema intractable in a patient with superior vena cava syndrome

Cutaneous lymphangitis carcinomatosa (CLC) is a rare form of cutaneous metastasis that causes lymphoedema and various eruptions. We report a case of lung cancer with CLC that caused both superior vena cava (SVC) stenosis and cervicofacial oedema, suggestive of SVC syndrome. A 64-year-old woman with lung adenocarcinoma presented with cervicofacial oedema and erythema, followed by severe dyspnoea 2 months after four cycles of carboplatin, pemetrexed and bevacizumab triplet therapy. Although chest CT indicated SVC stenosis, cervicofacial oedema remained despite treating the SVC stenosis via balloon dilation. A skin biopsy of the erythematic sample confirmed CLC as the cause of the patient’s symptoms. CLC should be considered as a differential diagnosis of cervicofacial oedema in addition to SVC syndrome, especially when it is observed in combination with skin erythema and induration. Moreover, a skin biopsy should be performed promptly for accurate diagnosis of CLC and to decide on appropriate treatment.