Papers - HOSOKAWA Ayumu
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The Efficacy and Safety of Nivolumab Plus mFOLFOX6 in Gastric Cancer with Severe Peritoneal Metastasis. Reviewed
Nakayama Y, Ando T, Takahashi N, Tsukada K, Takagi H, Goto Y, Nakaya A, Nakada N, Yoshita H, Motoo I, Ueda A, Ueda Y, Sakumura M, Kajiura S, Ogawa K, Hosokawa A, Yasuda I
Journal of clinical medicine 13 ( 3 ) 2024.1
Language：English Publishing type：Research paper (scientific journal)
DOI： 10.3390/jcm13030834
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Takagi H., Kajiura S., Hosokawa A., Horikawa N., Terada I., Hata T., Kobayashi Y., Tsukioka Y., Yabushita K., Matsuo T., Yoshita H., Ueda A., Ogawa K., Ando T., Hayashi R., Yasuda I.
Traditional and Kampo Medicine 10 ( 3 ) 278 - 284 2023.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Traditional and Kampo Medicine
Aim: 5-Fluorouracil/folinic acid and oxaliplatin plus bevacizumab (FOLFOX + BV) is a standard chemotherapy regimen for metastatic colorectal cancer (mCRC). This study was aimed at evaluating the preventive effects of shakuyakukanzoto against oxaliplatin-induced neurotoxicity associated with FOLFOX + BV administration. Methods: In this single-arm, open-label, phase II clinical trial, we enrolled patients with previously untreated, histologically confirmed mCRC from six hospitals in Japan who were aged 20 years and older and had an Eastern Cooperative Oncology Group performance status of 0–1. The patients received shakuyakukanzoto 2.5 g thrice daily, orally, until disease progression and/or unacceptable toxicity was noted. The primary endpoint was the incidence of neurotoxicity following oxaliplatin administration at a dose of 500 mg/m2. Neurotoxicity was evaluated according to the Neurotoxicity Criteria of Debiopharm (DEB-NTC). The trial was registered in the UMIN Clinical Trials Registry of Japan (UMIN000001853). Results: Forty-one non-pretreated mCRC patients were included between April 2009 and September 2013. At an oxaliplatin dose of 500 mg/m2, neurotoxicity of DEB-NTC grade 1–2 developed in 25.0% of patients; no patient had DEB-NTC grade 3 neurotoxicity. The most common grade 3/4 adverse events were neutropenia (34.1%), hypertension (24.4%), and fatigue (9.8%). The response rate of the 38 patients with measurable lesions was 55.2%. The median progression-free and overall survival was 14.9 and 35.2 months respectively. Conclusion: Shakuyakukanzoto substantially reduced oxaliplatin-induced neurotoxicity without negatively affecting tumor response or survival in FOLFOX + BV-treated patients with CRC.
DOI： 10.1002/tkm2.1389
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Motoo I., Ando T., Hamashima T., Kajiura S., Sakumura M., Ueda Y., Murayama A., Ogawa K., Tsukada K., Ueda A., Suzuki N., Nakada N., Nakashima K., Hosokawa A., Yasuda I.
Frontiers in Oncology 13 1193533 2023.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers in Oncology
Introduction: The efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patients with GC, and we analyzed its mechanism focusing on the intratumoral immune cells. Methods: Patients who received ICIs were retrospectively classified into non-systemic and systemic progression groups based on their radiological assessments. Moreover, the best percentage change in target lesions from each organ was compared. Results: Among 148 patients, the non-systemic progression group showed a significant improvement in overall survival (OS) compared with the systemic progression group (median, 5.6 months vs. 3.3 months; HR, 0.53; 95%CI, 0.32–0.89; p = 0.012). Poor performance status (HR, 1.73, 95%CI, 1.00–2.87) and systemic progression (HR, 3.09, 95%CI, 1.95–4.82) were associated with OS. Of all metastatic sites, the liver showed the poorest percentage change, and liver metastasis (OR, 2.99, 95%CI, 1.04–8.58) was associated with systemic progression. Hence, intratumoral CD8+ T-cell density was lower in patients with liver metastasis than in those without liver metastasis after ICIs, although the density of CD4+ T-cells (Th1, Th17, and Treg) and CD163+ cells (TAM) were not significantly different. Conclusion: The new progression pattern was associated with OS in GC. Liver metastasis may be a predictive factor of systemic progression during ICIs by regulating intratumoral CD8+ T-cells.
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Kai K., Hamada T., Sato Y., Hiyoshi M., Imamura N., Yano K., Ikeda T., Ichihara A., Ogata S., Choijookhuu N., Hishikawa Y., Hosokawa A., Nanashima A.
Journal of Oncology 2023 1440257 2023.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Oncology
Background. Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Methods. Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Results. Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Conclusions. Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy.
DOI： 10.1155/2023/1440257
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Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer. Reviewed
Ando T, Hosokawa A, Sakumura M, Motoo I, Kajiura S, Hirano K, Miwa T, Yokota T, Nakada N, Ueda Y, Ueda A, Tsukada K, Ogawa K, Nakaya A, Teramoto A, Nanjo S, Mihara H, Fujinami H, Fujii T, Yasuda I
Oncology 101 ( 1 ) 59 - 68 2023.1
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Feasibility of edoxaban for asymptomatic cancer-associated thrombosis in Japanese patients with gastrointestinal cancer: ExCAVE study. Reviewed
Nakamura M, Ishiguro A, Dazai M, Kawamoto Y, Yuki S, Sogabe S, Hosokawa A, Sawada K, Muto O, Izawa N, Nakashima K, Horie Y, Yagisawa M, Kajiura S, Ando T, Mitsuhashi Y, Sunakawa Y, Kikuchi Y, Komatsu Y
BMC cancer 22 ( 1 ) 1322 2022.12
Language：English Publishing type：Research paper (scientific journal)
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Efficacy and Safety of FOLFOX in Advanced Gastric Cancer Initially Presenting With Disseminated Intravascular Coagulation. Reviewed
Takahashi N, Ando T, Motoo I, Sakumura M, Ueda Y, Kajiura S, Nakashima K, Hosokawa A, Ueda A, Suzuki N, Nakaya A, Yasuda I
In vivo (Athens, Greece) 36 ( 5 ) 2447 - 2452 2022.9
Language：English Publishing type：Research paper (scientific journal)
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Rare resected eight cases of duodenal adenocarcinomas. Reviewed
Nanashima A, Tanoue Y, Imamura N, Hiyoshi M, Yano K, Hamada T, Nishida T, Kai K, Suzuki Y, Sato Y, Nakashima K, Hosokawa A, Nagayasu T
International journal of surgery case reports 86 106384 2021.9
Language：English Publishing type：Research paper (scientific journal)
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A phase II study of chemoselection with docetaxel, cisplatin, and 5–fluorouracil as a strategy for organ preservation in patients with resectable esophageal cancer (CROC trial).
Chikatoshi Katada, Hiroki Hara, Hirofumi Fujii, Takako Eguchi Nakajima, Takayuki Ando, Motoo Nomura, Takashi Kojima, Keishi Yamashita, Tetsuji Yokoyama, Yasutoshi Sakamoto, Hiroki Sasaki, Yusuke Inoue, Shogo Kawakami, Hideki Ishikawa, Ayumu Hosokawa, Yasuo Hamamoto, Manabu Muto, Makoto Tahara, Wasaburo Koizumi
Journal of Clinical Oncology 39 ( 15_suppl ) 4027 - 4027 2021.5
Publishing type：Research paper (scientific journal) Publisher：American Society of Clinical Oncology (ASCO)
<jats:p> 4027 </jats:p><jats:p> Background: In patients with resectable esophageal squamous cell carcinoma (SCC), the outcomes of chemoradiotherapy (CRT) for good responders after three courses of induction chemotherapy (IC) with docetaxel, cisplatin, and 5–fluorouracil (DCF chemotherapy) were unclear. Methods: Patients with clinical stage IB–III (UICC 7th) resectable esophageal SCC were eligible. IC included docetaxel 75 mg/m<jats:sup>2</jats:sup> on day 1, cisplatin 75 mg/m<jats:sup>2</jats:sup> on day 1, and 5–fluorouracil 750 mg/m<jats:sup>2</jats:sup> on days 1–5, repeated every 3 weeks for 3 cycles. The response was evaluated after 2 and 3 courses of IC. Patients were considered to have a “remarkable response (RR)” if an endoscopic examination with a central review showed shrinking of the primary lesion equivalent to T1 and the short axis of the metastatic lymph nodes were all < 1 cm on computed tomography—in other words, down staging to T1N0M0 stage IA. Patients were considered to have a “poor response (POR)” if they had progressive disease or no signs of reduction. Patients who did not achieve RR or POR were deemed to have “limited partial response (LPR)”. CRT was administered to patients who achieved RR, and surgery was performed in patients who achieved LPR or POR. CRT included cisplatin 75 mg/m<jats:sup>2</jats:sup> on day 1 and 5–fluorouracil 1000 mg/m<jats:sup>2</jats:sup> on days 1–4, repeated every 4 weeks for 2 cycles. Radiotherapy was administered as 50.4 Gy in 28 fractions. The primary endpoint was a 1–year progression free survival (PFS) for RR followed by CRT. Results: A total of 92 patients were enrolled. Two patients with non–SCC (n = 1) and distant metastasis (n = 1) were excluded. Therefore, 90 patients were included in the analysis group. Although 1 patient could not continue IC due to renal failure, the remaining 89 patients completed 3 courses of IC. The response after IC were RR in 58.4% (52/89), LPR in 41.6% (37/89), and POR in 0.0% (0/89). Three patients who achieved RR underwent surgery owing to renal dysfunction (n = 1), curative irradiation difficulty due to intestinal malrotation (n = 1), and CRT refusal (n = 1). Six patients who achieved LPR underwent CRT owing to surgery refusal (n = 3), unresectable tumors (n = 2), and respiratory dysfunction due to emphysema (n = 1). The complete response rate for RR followed by CRT was 89.8%. During the median follow–up period of 33 months (range: 1–85), the 1 and 3–years overall survival (OS) for the analysis group were 96.6% and 74.1%, respectively. The 1 and 3–years organ preservation survival for the analysis group were 56.8% and 45.3%, respectively. The 1 and 3–years OS for RR followed by CRT (n = 49) vs. LPR followed by surgery (n = 31) were 100% vs. 93.1% and 83.7% vs. 62.8%, respectively (p = 0.06). The 1 and 3–years PFS for RR followed by CRT were 89.8% and 70.0%, respectively. Conclusions: Three courses of DCF chemotherapy followed by CRT is an effective treatment for patients with resectable esophageal SCC who respond to the IC regimen. Clinical trial information: 8086. </jats:p>
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Katada C., Sugawara M., Hara H., Fujii H., Nakajima T.E., Ando T., Kojima T., Watanabe A., Sakamoto Y., Ishikawa H., Hosokawa A., Hamamoto Y., Muto M., Tahara M., Koizumi W.
Japanese Journal of Clinical Oncology 51 ( 2 ) 199 - 204 2021.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology
Background: An exploratory study was designed to evaluate the efficacy of granulocyte colony stimulating factor support for chemotherapy consisting of docetaxel, cisplatin and 5-fluorouracil chemotherapy in patients with oesophageal cancer. Methods: The inclusion criteria were as follows: (1) oesophageal squamous cell carcinoma, (2) a schedule to receive three courses of induction chemotherapy (docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, 5-fluorouracil 750 mg/m2 days 1-5, every 3 weeks), (3) stage IB-III, (4) 20-75 years old, (5) 0-1 performance status, (6) preserved organ functions and (7) written informed consent. The endpoints were to evaluate the efficacy of granulocyte colony stimulating factor support including secondary prophylactic usage for docetaxel, cisplatin and 5-fluorouracil chemotherapy. Patients who previously had 'febrile neutropenia', or 'Grade 3 or 4 infection accompanied by grade 3 or 4 neutropenia' prophylactically received granulocyte colony stimulating factor support from day 7. Results: A total of 91 patients were included in the analysis. Granulocyte colony stimulating factor support was given to 81.3%. The incidence of grade 4 neutropenia and febrile neutropenia were 81.3 and 32.9%, respectively. The dose of anticancer agents was reduced in 48.4%. There were no treatment-related deaths. The relative dose intensity of docetaxel, cisplatin and 5-fluorouracil were 92.7 ± 9.8%, 86.0 ± 15.6% and 91.8 ± 10.0%, respectively. In the secondary prophylactic granulocyte colony stimulating factor support group, the neutrophil count significantly increased between day 7 and day 13 as compared with the non-prophylactic granulocyte colony stimulating factor support group (P < 0.05 for each day). Conclusions: Granulocyte colony stimulating factor support including secondary prophylactic usage may be feasible for maintaining the intensity of docetaxel, cisplatin and 5-fluorouracil chemotherapy in patients with oesophageal cancer.
DOI： 10.1093/jjco/hyaa190
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Ioka T., Furuse J., Fukutomi A., Mizusawa J., Nakamura S., Hiraoka N., Ito Y., Katayama H., Ueno M., Ikeda M., Sugimori K., Okano N., Shimizu K., Yanagimoto H., Okusaka T., Ozaka M., Todaka A., Nakamori S., Tobimatsu K., Sata N., Kawashima Y., Hosokawa A., Yamaguchi T., Miyakawa H., Hara H., Mizuno N., Ishii H.
Japanese Journal of Clinical Oncology 51 ( 2 ) 235 - 243 2021.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology
Background: Chemoradiotherapy is a treatment option for locally advanced pancreatic cancer. However, the efficacy of induction chemotherapy prior to chemoradiotherapy is uncertain. The aim of this randomized, multicentre phase II study is to evaluate the efficacy and safety of chemoradiotherapy with and without induction chemotherapy to determine the significance of induction chemotherapy. Methods: Patients with locally advanced pancreatic cancer were randomly assigned to the chemoradiotherapy arm (Arm A) or induction chemotherapy followed by the chemoradiotherapy arm (Arm B). Patients in Arm A underwent radiotherapy with concurrent S-1. Patients in Arm B received induction gemcitabine for 12 weeks, and thereafter, only patients with controlled disease underwent the same chemoradiotherapy as Arm A. After chemoradiotherapy, gemcitabine was continued until disease progression or unacceptable toxicity in both arms. The primary endpoint was overall survival. Results: Amongst 102 patients enrolled, 100 were eligible for efficacy assessment. The probability of survival was greater in Arm B in the first 12 months, but the trend was reversed in the following periods (1-year survival 66.7 vs. 69.3%, 2-year survival 36.9 vs. 18.9%). The hazard ratio was 1.255 (95% confidence interval 0.816-1.930) in favour of Arm A. Gastrointestinal toxicity was slightly more frequent and three treatment-related deaths occurred in Arm A. Conclusions: This study suggested that the chemoradiotherapy using S-1 alone had more promising efficacy with longer-term survival, compared with induction gemcitabine followed by chemoradiotherapy for locally advanced pancreatic cancer. Clinical trial registration: The study was registered at the UMIN Clinical Trials Registry as UMIN000006811.
DOI： 10.1093/jjco/hyaa198
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KUROKI Daisuke, HOSOKAWA Ayumu, KAWAKAMI Hiroshi, NAKASHIMA Kouji, SUZUKI Sho, MIIKE Tadashi, ASHIZUKA Shinya, ABE Hiroo, YAMAMOTO Shojiro, INATSU Haruhiko
GASTROENTEROLOGICAL ENDOSCOPY 63 ( 2 ) 188 - 194 2021.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Gastroenterological Endoscopy Society
<p>A 37-year-old man underwent thymectomy for myasthenia gravis and subsequently received oral medication. Screening upper gastrointestinal endoscopy revealed a 20mm fading concave lesion on the posterior wall of the greater curvature of the stomach. He was diagnosed with signet-ring cell carcinoma based on histopathological examination of a biopsy specimen and was referred to our hospital for further management. Preoperative evaluation led to a diagnosis of early gastric cancer and he was scheduled for endoscopic submucosal dissection (ESD). Benzodiazepines are contraindicated for sedation in patients with myasthenia gravis, and a drug that does not cause muscle relaxation should be administered. Therefore, in this patient, we performed successful ESD using a combination of dexmedetomidine, pentazocine, and hydroxyzine for sedation. Dexmedetomidine is useful for limited sedation that is required during endoscopic procedures in patients with myasthenia gravis.</p>
DOI： 10.11280/gee.63.188
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Sakumura M., Ando T., Hosokawa A., Nakajima T., Motoo I., Mihara H., Ueda A., Kajiura S., Nanjo S., Fujinami H., Ogawa K., Yasuda I.
BMC Gastroenterology 20 ( 1 ) 355 2020.12
Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Gastroenterology
Background: Diarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, limited data are available on the frequency and risk factors of complicated chemotherapy-induced diarrhea (CID) and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE) and determined baseline risk factors associated with complicated CID. Methods: In total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID. Results: Total number of 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 25 (78%) patients, with cramping, vomiting, and sepsis being observed in 15 (60%), 8 (32%), and 3 (12%) patients, respectively. Among the 13 patients who underwent CE, 11 (85%) showed abnormal findings. Multivariate analysis revealed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio 2.95; 95% confidence interval 1.06–8.19). Conclusions: Despite the relatively low incidence of complicated CID, mucosal injury of small intestine was common in patients with complicated fluoropyrimidine-induced diarrhea and oral fluoropyrimidine was an independent risk factor.
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Okuyama H., Ikeda M., Okusaka T., Furukawa M., Ohkawa S., Hosokawa A., Kojima Y., Hara H., Murohisa G., Shioji K., Asagi A., Mizuno N., Kojima M., Yamanaka T., Furuse J.
Neuroendocrinology 110 ( 11-12 ) 988 - 993 2020.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Neuroendocrinology
Background: Platinum-containing regimens are widely used as first-line chemotherapy for unresectable pancreatic neuroendocrine carcinoma (NEC), but second-line chemotherapies have yet to be established. Objectives: We evaluated the safety and efficacy of everolimus in patients with pancreatic NEC refractory or intolerant to platinum-containing chemotherapy. Methods: This study was a prospective, multicenter, phase II trial in patients with pancreatic NEC after platinum-containing chemotherapy. Everolimus treatment was continued until disease progression or intolerable toxicity was observed. The primary endpoint was progression-free survival (PFS). Results: Participants comprised 25 patients. Median age was 63 years, median PFS was 1.2 months (95% confidence interval [CI] 0.9-3.1 months), median overall survival was 7.5 months (95% CI 3.1-13.5 months), overall response rate was 0%, and disease control rate was 39.1%. Common grade 3/4 adverse events were hyperglycemia (20%), thrombocytopenia (16%), and anemia (16%). Conclusion: The efficacy of everolimus was limited in patients with unresectable pancreatic NEC.
DOI： 10.1159/000505550
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Hosokawa A., Yamazaki K., Matsuda C., Ueda S., Kusaba H., Okamura S., Tsuda M., Tamura T., Shinozaki K., Tsushima T., Tsuda T., Shirakawa T., Yamashita H., Morita S., Hironaka S., Muro K.
Medicine 99 ( 36 ) e22060 2020.9
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Medicine
The phase III West Japan Oncology Group (WJOG) 4407G study showed noninferiority of folinic acid, bolus/continuous fluorouracil, and irinotecan plus bevacizumab to modified folinic acid, bolus/continuous fluorouracil, and oxaliplatin 6 plus bevacizumab in progression-free survival (PFS) as first-line chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to evaluate the predictive and prognostic value of morphologic response in patients with colorectal liver metastases (CLM) as a post hoc analysis of the WJOG4407G study.Morphologic response was assessed by comparing contrast-enhanced computed tomography (CT) images at baseline and week 8. Three blinded radiologists evaluated CT images and classified their response as optimal, incomplete, or no response according to the morphologic criteria. Response evaluation criteria in solid tumors (RECIST) response, early tumor shrinkage (ETS), and depth of response (DpR) were also evaluated.Among 395 patients who were eligible for efficacy analysis in the WJOG4407G study, 70 patients had liver-limited disease. We finally evaluated 55 of these patients. Optimal morphologic response was identified in 19 of 55 patients (34.5%). The median PFS was 10.7 months for patients with optimal response and 10.1 months in those with incomplete/no response (log-rank, P = .96). The median overall survival (OS) was 26.2 and 35.5 months, respectively (log-rank, P = .062). According to univariate analysis, morphologic response was not associated with PFS or OS, whereas RECIST response was significantly associated with both PFS and OS, with ETS and DpR being associated with significantly longer PFS.Morphologic response might be neither a predictive nor a prognostic factor in patients with CLM undergoing chemotherapy containing bevacizumab, whereas RECIST response was significantly associated with both PFS and OS.
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Sakai D., Taniguchi H., Sugimoto N., Tamura T., Nishina T., Hara H., Esaki T., Denda T., Sakamoto T., Okuda H., Satoh T., Tsushima T., Makiyama A., Tsuda T., Hosokawa A., Kuramochi H., Tokunaga S., Moriwaki T., Yasui H., Ishida H., Tsuji A., Otsu S., Shimokawa H., Baba E., Sato M., Matsumoto S., Ozaki Y., Shinozaki K., Tamagawa H., Goto M., Kadowaki S., Fujii H., Koh Y., Yamazaki K., Hironaka S., Kishimoto J., Boku N., Hyodo I., Muro K.
European Journal of Cancer 135 11 - 21 2020.8
Language：English Publishing type：Research paper (scientific journal) Publisher：European Journal of Cancer
Background: Cetuximab has been shown to be clinically active when given in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer (mCRC). However, it has remained unclear whether panitumumab is effective when combined with irinotecan. We compared efficacies of both regimens in this randomised phase II study. Patients and methods: Patients with wild-type KRAS exon 2 mCRC previously treated with fluorouracil-, oxaliplatin- and irinotecan-based chemotherapies were randomised (1:1) to either panitumumab plus irinotecan (panitumumab arm) or cetuximab plus irinotecan (cetuximab arm). The primary end-point was progression-free survival (PFS). The planned sample size was 120, expecting a hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (one-sided alpha error 0.2 and power 0.7). Major secondary end-points were overall survival (OS), response rate and safety. Results: From December 2011 to September 2014, 121 patients were enrolled, and 61 and 59 patients were randomised to the panitumumab and cetuximab arms, respectively (1 patient excluded). Most patients (97%) had received prior chemotherapies containing bevacizumab. The median PFS was 5.42 months in the panitumumab arm and 4.27 months in the cetuximab arm (HR = 0.64, 95% confidence interval [CI] = 0.44–0.94, P < 0.001 for non-inferiority, P = 0.058 for superiority), and median OS was 14.85 and 11.53 months (HR = 0.66, 95% CI = 0.44–1.00, P = 0.050 for superiority), respectively. The incidence of grade 3 or 4 hypomagnesaemia was higher in the panitumumab arm than that in the cetuximab arm (17% vs. 7%). Conclusion: Panitumumab may be non-inferior to cetuximab in combination with irinotecan in survival of patients with irinotecan-refractory mCRC.
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Makiyama A., Sukawa Y., Kashiwada T., Kawada J., Hosokawa A., Horie Y., Tsuji A., Moriwaki T., Tanioka H., Shinozaki K., Uchino K., Yasui H., Tsukuda H., Nishikawa K., Ishida H., Yamanaka T., Yamazaki K., Hironaka S., Esaki T., Boku N., Hyodo I., Muro K.
Journal of Clinical Oncology 38 ( 17 ) 1919 - 1927 2020.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Clinical Oncology
PURPOSE This study evaluated the continuous use of trastuzumab beyond progression (TBP) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. PATIENTS AND METHODS Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m2, days 1, 8, and 15, every 4 weeks) or paclitaxel with trastuzumab (PT; initially 8 mg/kg followed by 6 mg/kg, every 3 weeks) arms. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety. Biomarkers such as HER2 expression status in tumor tissue after first-line treatment, HER2 amplification evaluated in serum cell-free DNA, and soluble HER2 levels were analyzed. RESULTS Overall, 91 patients were allocated to the paclitaxel (n = 46) and PT (n = 45) arms. The median PFS in the paclitaxel and PT arms was 3.2 and 3.7 months, respectively (hazard ratio [HR], 0.91; 80% CI, 0.67 to 1.22; P = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; P = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively (P = 1.00), and safety was comparable between the 2 arms. On exploratory analyses, HER2 positivity of tumor tissues was lost after first-line chemotherapy in 11 (69%) of 16 patients whose tumor tissues were available, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients. However, no biomarkers associated with efficacy of TBP were found. CONCLUSION The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.
DOI： 10.1200/JCO.19.03077
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Shitara K., Hara H., Yoshikawa T., Fujitani K., Nishina T., Hosokawa A., Asakawa T., Kawakami S., Muro K.
International Journal of Clinical Oncology 25 ( 2 ) 301 - 311 2020.2
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Clinical Oncology
Background: The phase III JACOB trial (NCT01774786) compared the efficacy and safety of pertuzumab and trastuzumab plus chemotherapy with placebo and trastuzumab plus chemotherapy in patients with previously untreated human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric or gastroesophageal junction cancer. We conducted a subgroup analysis in Japanese patients. Methods: Patients were randomized 1:1 to pertuzumab 840 mg or placebo, plus trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) and chemotherapy (cisplatin 80 mg/m2, and capecitabine 1000 mg/m2 twice daily for 28 doses or 5-fluorouracil 800 mg/m2 every 24 h for 120 h), every 3 weeks. Continuation of chemotherapy after 6 cycles was at the discretion of the patient and the treating physician. Results: A total of 40 Japanese patients were included in each arm. Median overall survival was 22.0 months (95% confidence interval [CI] 13.8–not evaluable) and 15.6 months (95% CI 9.7–19.2) in the pertuzumab and placebo arms, respectively (hazard ratio [HR] 0.64 [95% CI 0.37–1.10]). Median progression-free survival was 12.4 months (95% CI 6.1–14.1) in the pertuzumab arm and 6.3 months (95% CI 4.3–8.1) in the placebo arm (HR 0.50 [95% CI 0.30–0.82]). Grade ≥ 3 adverse events and serious adverse events were more frequent in the pertuzumab arm than the placebo arm. Conclusions: Results from this subgroup analysis of the JACOB trial suggest similar efficacy of pertuzumab in Japanese patients and patients in the overall population, encouraging continued investigation of new agents for gastric cancer in Japanese patients.
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Kawano F., Yonekawa T., Yamaguchi H., Shibata N., Tashiro K., Ikenoue M., Munakata S., Higuchi K., Tanaka H., Sato Y., Hosokawa A., Takeno S., Nakamura K., Nanashima A.
Endocrinology, Diabetes and Metabolism Case Reports 2020 ( 1 ) 1 - 6 2020.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Endocrinology, Diabetes and Metabolism Case Reports
A 54-year-old woman was referred to our hospital with a cervical tumor. CT revealed a cervical tumor extending to the upper mediastinum, tracheal deviation and tumor infiltration in the cervical vessels. She was followed-up because no diagnosis of malignancy was made by cytology. However, 2 months later, a CT scan showed enlargement of the tumor and tracheal stenosis, and a surgical biopsy was performed and she was diagnosed with anaplastic thyroid cancer (ATC). The tracheal tube with tracheal stenosis could not be removed due to the rapid growth of the tumor, necessitating management by mechanical ventilation. Due to the difficulty of surgical resection, she was treated with lenvatinib. A lenvatinib solution was made and administered via a nasogastric tube. After lenvatinib treatment, the tumor volume decreased and the tracheal stenosis improved. The tracheal tube was removed and oral intake became possible. She was discharged and received ambulatory lenvatinib therapy. The tumor was significantly reduced in size, but gradually grew and was exposed through the cervical wound 6 months later. Esophageal perforation occurred 10 months after the start of treatment. Lenvatinib was re-administered via a nasogastric tube. Eleven months later, the patient died of massive bleeding from the exposed cervical tumor. Patients with advanced ATC may require management with mechanical ventilation for airway stenosis or with a nasogastric tube for esophageal stenosis and perforation. We experienced a case in which lenvatinib was safely administered via a nasogastric tube while performing mechanical ventilation.
DOI： 10.1530/EDM-20-0064
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Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Reviewed
Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J.
Ann Oncol 2019
Language：English Publishing type：Research paper (scientific journal)