Shinnosuke Takemoto

Interstitial pneumonia probably associated with sorafenib treatment: An alert of an adverse event

There has been no literature which reports a case of interstitial lung disease associated with sorafenib. However, a recent post-marketing survey in Japan revealed that interstitial pneumonia occurred in 4 among approximately 2 000 Japanese patients treated with sorafenib. In this article, we describe a Japanese patient with severe interstitial pneumonia probably caused by sorafenib treatment for metastatic renal cell carcinoma. Oncologists supervising future clinical trials for lung cancer should be alert to the fact that sorafenib can potentially induce serious interstitial lung disease, although this might depend on racial differences.

Relationship between UGT1A1*27 and UGT1A1*7 polymorphisms and irinotecan-related toxicities in patients with lung cancer

The objective of this study was to evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy.

Phase I study of pemetrexed and concurrent radiotherapy for previously untreated elderly patients with locally advanced non-squamous non-small cell lung cancer

Chemoradiotherapy is the standard treatment for locally advanced non‐small cell lung cancer (NSCLC); however, it is disputed whether this treatment is suitable for patients aged ≥75. This study was conducted to determine the maximum tolerated dose (MTD) of pemetrexed for use in concurrent radiotherapy for elderly patients with locally advanced non‐squamous NSCLC.

Pulmonary Artery Sarcoma Overexpressing Platelet-derived Growth Factor Receptor α

Pulmonary artery sarcoma is highly malignant and easily metastasizes to the systemic organs. Both the introduction of novel diagnostic procedures and the development of new treatment modalities are required to achieve long-term survival. Several studies have shown that platelet-derived growth factor receptor α (PDGFRα) gene amplification is frequently observed in pulmonary artery sarcoma. PDGFRα is known to be involved in cell proliferation in certain malignancies. PDGFRα may become a potential biological marker in pulmonary artery sarcoma. We report a case in which a diagnosis of pulmonary artery sarcoma overexpressing PDGFRα was made using endovascular catheter biopsy following positron emission tomography with integrated computed tomography (PET/CT) scans.

Abstract 5032: The relationship between theUGT1A1*27andUGT1A1*7genetic polymorphisms and irinotecan-related toxicities in patients with lung cancer

Background: Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1), UGT1A7, and UGT1A9 genes are associated with interindividual differences in irinotecan toxicities. The UGT1A1*7, *27, and *29 gene polymorphisms occur within the common exons of UGT1A1 isoforms and cause substantial reductions in their functional activity; however, few clinical studies have examined the effects of these polymorphisms. Purpose: To evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy. Patients and methods: The eligibility criteria were as follows: lung cancer patients who were scheduled to undergo irinotecan therapy, aged ≥20 years, and had a performance status of 0-2. After informed consent had been obtained, patients were enrolled, and their blood was collected and used to examine the frequency of the UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the drug concentrations of irinotecan, SN-38, and SN-38G after irinotecan therapy. Results: Thirty-one patients were enrolled. The patients’ characteristics were as follows: male/female = 25/6, median age (range) = 71 (55-84), stage IIB/IIIA/IIIB/IV = 2/6/11/12, and Ad/Sq/Sm/Oth = 14/10/3/4. The -/-, *6/-, *7/-, *27/-, *28/-, and *29/- UGT1A1 gene polymorphisms were observed in 10 (32%), 10 (32%), 2 (6%), 2 (6%), 7 (23%), and 0 (0%) cases, respectively. There were no homozygous or complex heterozygous polymorphisms. The UGT1A1*27 polymorphism occurred separately from the UGT1A1*28 polymorphism. The lowest leukocyte counts of the patients with the UGT1A1*27 and UGT1A1*6 gene polymorphisms were lower than those seen in the wild-type patients. SN-38 tended to remain in the blood for a prolonged period after the infusion of irinotecan in patients with the UGT1A1*27 or UGT1A1*28 polymorphism. No severe myelotoxicity was seen in the patients with UGT1A1*7. Conclusions: UGT1A1*27 and UGT1A1*7 are both rare gene polymorphisms. UGT1A1*27 can occur separately from UGT1A1*28 in some circumstances and is related to leukopenia during irinotecan treatment. UGT1A1*7 is less relevant to irinotecan-induced toxicities, and UGT1A1*29 seems to have little clinical impact. Citation Format: Minoru Fukuda, Manabu Okumura, Tomomi Iwakiri, Arimori Kazuhiko, Shinnosuke Takemoto, Takaya Ikeda, Takuya Honda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Kazuma Kobayashi, Mitsuko Masutani, Mikio Oka, Kazuto Ashizawa, Hiroshi Mukae. The relationship between the UGT1A1*27 and UGT1A1*7 genetic polymorphisms and irinotecan-related toxicities in patients with lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5032. doi:10.1158/1538-7445.AM2017-5032

Phase I/II study of amrubicin and nedaplatin in patients with untreated, advanced, non-small cell lung cancer.

A phase I/II study of combination chemotherapy with amrubicin and nedaplatin for patients with untreated, advanced, non-small cell lung cancer (NSCLC) was conducted. Amrubicin was given on days 1-3, with nedaplatin given on day 1. The treatment was repeated every 3 weeks. In the phase I trial, the initial amrubicin dose of 25 mg/m2 was escalated in 5-mg/m2 increments until the maximum tolerated dose was reached, with the dose of nedaplatin fixed at 100 mg/m2. In the phase II trial, the primary endpoint was the overall response rate (ORR), assuming 20% for a standard therapy and 40% for a target therapy (α = 0.05 and β = 0.20), and the estimated required total number of patients was 35. In the phase I study, nedaplatin 100 mg/m2 and amrubicin 25 mg/m2 was recommended. In the phase II study, 17 out of 35 patients achieved a partial response, and the ORR was 48.6%. Grade 3/4 neutropenia, grade 3 anemia and grade 3/4 thrombocytopenia occurred in 62.9, 11.4 and 11.4% of cycles, respectively. Febrile neutropenia occurred in 5 cycles (3.9%) and all cases were manageable. The recommended dose of this combination is well tolerated and effective in patients with advanced NSCLC.