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Papers by Masanori Toyoda

Microsatellite instability-high colorectal cancer patient-derived xenograft models for cancer immunity research

Journal of Cancer Research and Therapeutics

Phase 1 study of Gemcitabine/Nab-paclitaxel/S-1 in patients with unresectable pancreatic cancer (GeNeS1S trial)

Cancer Chemotherapy and Pharmacology

Phase I study of the antiprogrammed cell death‐1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies

Cancer Science

Abstract 653: A comparative analysis of pathological features and molecular genetics between salivary duct carcinoma and adenocarcinoma, not otherwise specified

Clinical Research (Excluding Clinical Trials)

P1-006Remarkable response to cetuximab-containing chemotherapy for tongue cancer refractory to immune checkpoint inhibitors

Annals of Oncology

Annals of Oncology

Background: Spartalizumab, a humanized IgG4 anti-PD1 mAb, blocks interaction with the ligand PD-L... more Background: Spartalizumab, a humanized IgG4 anti-PD1 mAb, blocks interaction with the ligand PD-L1. Previously published clinical data show a favorable safety profile and antitumor activity in non-Japanese patients (pts). Methods: This Phase I, open-label, dose-escalation study (NCT02678260) characterized the safety, PK, and efficacy of spartalizumab in Japanese pts with advanced malignancies who progressed on standard therapy. The primary objective was to determine the recommended dose (RD)/maximum tolerated dose (MTD). Results: 18 pts received spartalizumab Q2W in 3 dose groups: 1, 3, and 10 mg/kg (n ¼ 6 each). Median age was 53 yrs (range 29-75), 39% of pts were male, 83% had received !3 prior medications (all were pretreated). Most common cancer types were ovarian (17%), head and neck, cervical, and triple negative breast cancer (11% each). No DLTs were reported at any tested dose; MTD was not reached. Treatment-related AEs were reported for 11 pts (61%); most commonly (>10%) maculopapular rash (22%), malaise, alkaline phosphatase increased (each 11%). Treatment-related G3/G4 AEs (1 pt each, 6%) were creatine phosphokinase increased and alkaline phosphatase increased. ORR (per RECIST 1.1) was 11% (2/18); partial responses were seen in pts with HCC and transitional cell carcinoma. Stable disease was the best overall response in 22% of pts (4/18); disease control rate was 33%. PK exposure increased dose-proportionally, half-life was 12-22 days, and AUC accumulation was approximately 2-fold. PK data did not suggest ethnic difference. Conclusion: Spartalizumab was well tolerated in Japanese pts. As safety and PK profiles were comparable with previous trials in non-Japanese pts, RDs selected for non-Japanese pts (400 mg Q4W; 300 mg Q3W) were considered suitable for Japanese pts (pending further investigation). Preliminary efficacy was observed in a heavily pretreated and heterogenous population. Data support further clinical development of spartalizumab for Japanese pts.

Efficacy of the Two-Dose Influenza Vaccine in Cancer Patients Receiving Chemotherapy: A Prospective Study

Blood

Background: Cancer patients who are receiving chemotherapy are at risk for influenza infections a... more Background: Cancer patients who are receiving chemotherapy are at risk for influenza infections and its severe complications. Although influenza vaccination is recommended, preliminary data have raised questions about the immune response to vaccination in such patients. Furthermore, recent studies suggest that some tyrosine kinase inhibitors (TKIs) induce significant impairment of B cell responses and reduce vaccine efficacy. The two-dose influenza vaccination is proposed to be one of the strategies to increase the efficacy of influenza vaccination in cancer patients, but its efficacy has yet to be confirmed. Methods: This was a prospective multicenter study to evaluate the efficacy of the two-dose influenza vaccination in cancer patients receiving chemotherapy. We administered a triple-strain (A/California/7/2009 [H1N1], A/Texas/50/2012 [H3N2], and B/Massachusetts/2/2012) 2013/14 influenza vaccine to patients with pathologically confirmed malignancies. All patients were under the t...

Annals of Oncology

Background: Nivolumab improved overall survival (OS) in patients with platinumrefractory recurren... more Background: Nivolumab improved overall survival (OS) in patients with platinumrefractory recurrent or metastatic head and neck squamous cell carcinoma in the phase III CheckMate 141 clinical trial. Following this result, nivolumab was approved in Japan for recurrent or metastatic head and neck cancer regardless of histological subtype. However, the clinical efficacy of nivolumab for non-squamous head and neck cancer (non-Sq. HNC) remains unclear. Methods: To evaluate the efficacy of nivolumab for non-Sq. HNC, we retrospectively reviewed 28 patients (pts) treated with nivolumab for recurrent or metastatic head and neck cancer at our institution between March 2017 and January 2018. Results: Among the 28 pts, we identified 5 pts with recurrent or metastatic non-Sq. HNC. These 5 pts all received prior platinum-based chemotherapy, with 4 pts having platinum-refractory disease and 1 intolerant to platinum. Primary site was salivary glands/hypopharynx in 4/1. Pathological diagnosis was adeno carcinoma/basaloid carcinoma/salivary duct carcinoma/carcinoma ex-pleomorphic adenoma in 2/1/1/1, respectively. Median age (range) was 63 (58-81), and male/female was 4 /1. Four pts received at least 4 cycles of nivolumab, with a median cycle of 4 (1-15). According to RECIST ver1.1, one patient achieved PR, 2 pts showed SD and 2 pts had PD, corresponding to a disease control rate of 60%. The safety profile was equivalent to those in previous reports and no severe adverse reactions were seen. Conclusions: Nivolmab appeared to be beneficial and well-tolerated in pts with non-Sq. HNC and warrants further investigation for this rare disease subtype.

Exploratory analysis of prognostic factors for lenvatinib in radioiodine‐refractory differentiated thyroid cancer

Head & Neck

Case Reports in Oncology

Standard therapy for radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) is m... more Standard therapy for radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) is multi-targeted kinase inhibitors (m-TKIs), represented by sorafenib and lenvatinib. One of the main target molecules of m-TKIs is vascular endothelial growth factor receptor (VEGF-R). m-TKIs are known to cause adverse reactions such as hypertension and proteinuria as a class effect. In particular, proteinuria is thought to result from vascular endothelial damage and podocytopathy in glomeruli, and the development of thrombotic microangiopathy (TMA) has been reported for VEGF inhibitors. We encountered a patient with RAI-refractory (RR) papillary thyroid carcinoma (PTC) who developed proteinuria and renal dysfunction due to lenvatinib. Renal biopsy demonstrated that these changes were caused by TMA. To our knowledge, this is the first reported case of TMA due to lenvatinib in a Japanese patient with RR-PTC. A 70-year-old woman developed proteinuria, renal impairment and hypertension while ...

Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site

Journal of Clinical Oncology

PURPOSE Although gene expression profiling is a promising diagnostic technique to determine the t... more PURPOSE Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP. PATIENTS AND METHODS Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate. RESULTS One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in ...

Auris, nasus, larynx, 2018

Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory di... more Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib. She continued to receive lenvatinib but with repeated dose interruptions and reductions due to continuous proteinuria. Because of severe and persistent proteinuria as well as newly developed renal impairment, lenvatinib was suspended after two years of treatment. After the 7-month suspension, her proteinuria and renal impairment were partially improved, but her lung metastases progressed. Because she was unable to tolerate pre...

Oncotarget, Jan 6, 2018

The development of skin rashes is the most common adverse event observed in cancer patients treat... more The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm; = 0.009 in paired -test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm; = 0.028 in paired -test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, < 0.0001). Focal distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin r...

A phase I study for adjuvant chemotherapy of gemcitabine plus S-1 in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1202)

Cancer chemotherapy and pharmacology, 2018

To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected ... more To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy. A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1-14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level - 1), and 800/50 (Level - 2). Thirty-one patients (17 men and 14 women; median age, 70 years) were enrolled. Level 1 was chosen as the starting dose. Three of seven patients developed dose-limiting toxicities at Level 1 and the dose was de-escalated to Level - 1. Five of 12 patients developed Grade 4 neutropenia at Level - 1 and the dose was de-escalated to Level - 2. One patient developed Grade 4 neutropenia at Level - 2. Another patient was unable to receive the day 8 dose due to Grade 3 neutropenia at Level - 2. Level - 1 was confi...

O1-20-3A Prospective Study of the Efficacy of Influenza Vaccination for Cancer Patients Receiving Chemotherapy

Annals of Oncology, 2014

O1-6-4A Retrospective Analysis of Dacarbazine Monotherapy for Recurrent or Metastatic Mucosal Melanoma

Annals of Oncology, 2014

O1-4-1Relationship between Adverse Events and Efficacy of Lenvatinib for Thyroid Cancer

Annals of Oncology, 2016

International journal of hematology, 2017

Constitutional translocations that coincide with t(9;22)(q34;q11.2) may lead to unnecessary treat... more Constitutional translocations that coincide with t(9;22)(q34;q11.2) may lead to unnecessary treatments in chronic myeloid leukemia (CML) patients, as, under the standard criteria, a diagnosis of CML with additional chromosomal abnormalities indicates an accelerated phase (AP). In the present report, a 47-year-old male had pain in the right foot due to gout. Peripheral blood examination showed leukocytosis with left shift. Bone marrow aspiration revealed myeloid hyperplasia with megakaryocytosis. RT-PCR revealed the major BCR-ABL fusion transcript, and CML in the chronic phase was diagnosed, followed by nilotinib treatment. Although WBC counts decreased immediately, G-banding analysis showed 46,XY,t(8;22)(q24;q11.2),t(9;22)(q34;q11.2) [20]. The t(8;22)(q24;q11.2) translocation is known to be recurrent in Burkitt's lymphoma. The diagnosis was changed to CML in AP, leading to B-lymphoid crisis. Unexpectedly, the karyotype was 46,XY,t(8;22)(q24;q11.2) [20] in hematological complete ...

Anticancer Research, Jul 1, 2014

Aim: We evaluated the potential of TYRO3 as a therapeutic target in various types of breast cance... more Aim: We evaluated the potential of TYRO3 as a therapeutic target in various types of breast cancer cell lines. Materials and Methods: The effects of TYRO3-knockdown by small interfering RNA (siRNA) on proliferation, cell-cycle distribution, and cell signaling in four estrogen receptor (ER)-positive/HER2-non-amplified (luminal-type), two ERnegative/HER2-amplified (HER2-type), and two ERnegative/HER2-non-amplified (triple negative [TN]-type) cell lines were compared. Results: Whereas TYRO3 knockdown induced the greatest proliferation suppression in luminaltype cells, and to a lesser extent in HER2-type cells, no proliferation inhibition was observed in TN-type cells. The TYRO3 siRNA-induced proliferation inhibition in luminaltype cells was observed in both estradiol (E2)-rich and-null conditions. The proliferation suppression was correlated with G0-G1/S cell-cycle arrest. Western blot analysis showed a decrease in phosphorylation of ERK1/2 or STAT3, and in cyclin D1 only in cell lines sensitive to TYRO3-knockdown. Conclusion: TYRO3 is a potential therapeutic target in breast cancer, particularly in luminal-type cells.

Japanese Journal of Clinical Oncology, 2016

Objective: Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. ... more Objective: Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. Twodose vaccination is a proposed strategy for increasing vaccination efficacy; however, this has yet to be confirmed in this population. The purpose of this study was to clarify the efficacy and safety of this strategy. Methods: We conducted a multicentre prospective study on a two-dose vaccination regimen in cancer patients receiving chemotherapy. Second vaccinations were performed in patients who did not respond to all three viral strains after the first vaccination. Serum haemagglutination inhibition titres were measured to determine the patients' immunological response, 2 weeks prior to the first vaccination, 3-5 weeks after each vaccination, and at the end of the influenza season. Results: We enrolled 109 patients, including 70 with solid tumours, 36 with haematological malignancies, and 3 with both cancer types. Among the total patients, the proportion of patients with protective titres against the three viral strains increased significantly from 3 to 27% (P < 0.01) following vaccination. Among the 79 patients who received a second vaccination, the proportion of those with protective titres against the individual strains increased by 10% (H1N1), 8% (H3N2), and 3% (B) compared with after the first vaccination. Serious adverse events were not observed. Conclusions: We recommend influenza vaccinations for cancer patients, including those receiving chemotherapy. Also, the additional benefit of the second vaccination may be limited.

Microsatellite instability-high colorectal cancer patient-derived xenograft models for cancer immunity research

Journal of Cancer Research and Therapeutics

Phase 1 study of Gemcitabine/Nab-paclitaxel/S-1 in patients with unresectable pancreatic cancer (GeNeS1S trial)

Cancer Chemotherapy and Pharmacology

Phase I study of the antiprogrammed cell death‐1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies

Cancer Science

Abstract 653: A comparative analysis of pathological features and molecular genetics between salivary duct carcinoma and adenocarcinoma, not otherwise specified

Clinical Research (Excluding Clinical Trials)

P1-006Remarkable response to cetuximab-containing chemotherapy for tongue cancer refractory to immune checkpoint inhibitors

Annals of Oncology

Annals of Oncology

Background: Spartalizumab, a humanized IgG4 anti-PD1 mAb, blocks interaction with the ligand PD-L... more Background: Spartalizumab, a humanized IgG4 anti-PD1 mAb, blocks interaction with the ligand PD-L1. Previously published clinical data show a favorable safety profile and antitumor activity in non-Japanese patients (pts). Methods: This Phase I, open-label, dose-escalation study (NCT02678260) characterized the safety, PK, and efficacy of spartalizumab in Japanese pts with advanced malignancies who progressed on standard therapy. The primary objective was to determine the recommended dose (RD)/maximum tolerated dose (MTD). Results: 18 pts received spartalizumab Q2W in 3 dose groups: 1, 3, and 10 mg/kg (n ¼ 6 each). Median age was 53 yrs (range 29-75), 39% of pts were male, 83% had received !3 prior medications (all were pretreated). Most common cancer types were ovarian (17%), head and neck, cervical, and triple negative breast cancer (11% each). No DLTs were reported at any tested dose; MTD was not reached. Treatment-related AEs were reported for 11 pts (61%); most commonly (>10%) maculopapular rash (22%), malaise, alkaline phosphatase increased (each 11%). Treatment-related G3/G4 AEs (1 pt each, 6%) were creatine phosphokinase increased and alkaline phosphatase increased. ORR (per RECIST 1.1) was 11% (2/18); partial responses were seen in pts with HCC and transitional cell carcinoma. Stable disease was the best overall response in 22% of pts (4/18); disease control rate was 33%. PK exposure increased dose-proportionally, half-life was 12-22 days, and AUC accumulation was approximately 2-fold. PK data did not suggest ethnic difference. Conclusion: Spartalizumab was well tolerated in Japanese pts. As safety and PK profiles were comparable with previous trials in non-Japanese pts, RDs selected for non-Japanese pts (400 mg Q4W; 300 mg Q3W) were considered suitable for Japanese pts (pending further investigation). Preliminary efficacy was observed in a heavily pretreated and heterogenous population. Data support further clinical development of spartalizumab for Japanese pts.

Efficacy of the Two-Dose Influenza Vaccine in Cancer Patients Receiving Chemotherapy: A Prospective Study

Blood

Background: Cancer patients who are receiving chemotherapy are at risk for influenza infections a... more Background: Cancer patients who are receiving chemotherapy are at risk for influenza infections and its severe complications. Although influenza vaccination is recommended, preliminary data have raised questions about the immune response to vaccination in such patients. Furthermore, recent studies suggest that some tyrosine kinase inhibitors (TKIs) induce significant impairment of B cell responses and reduce vaccine efficacy. The two-dose influenza vaccination is proposed to be one of the strategies to increase the efficacy of influenza vaccination in cancer patients, but its efficacy has yet to be confirmed. Methods: This was a prospective multicenter study to evaluate the efficacy of the two-dose influenza vaccination in cancer patients receiving chemotherapy. We administered a triple-strain (A/California/7/2009 [H1N1], A/Texas/50/2012 [H3N2], and B/Massachusetts/2/2012) 2013/14 influenza vaccine to patients with pathologically confirmed malignancies. All patients were under the t...

Annals of Oncology

Background: Nivolumab improved overall survival (OS) in patients with platinumrefractory recurren... more Background: Nivolumab improved overall survival (OS) in patients with platinumrefractory recurrent or metastatic head and neck squamous cell carcinoma in the phase III CheckMate 141 clinical trial. Following this result, nivolumab was approved in Japan for recurrent or metastatic head and neck cancer regardless of histological subtype. However, the clinical efficacy of nivolumab for non-squamous head and neck cancer (non-Sq. HNC) remains unclear. Methods: To evaluate the efficacy of nivolumab for non-Sq. HNC, we retrospectively reviewed 28 patients (pts) treated with nivolumab for recurrent or metastatic head and neck cancer at our institution between March 2017 and January 2018. Results: Among the 28 pts, we identified 5 pts with recurrent or metastatic non-Sq. HNC. These 5 pts all received prior platinum-based chemotherapy, with 4 pts having platinum-refractory disease and 1 intolerant to platinum. Primary site was salivary glands/hypopharynx in 4/1. Pathological diagnosis was adeno carcinoma/basaloid carcinoma/salivary duct carcinoma/carcinoma ex-pleomorphic adenoma in 2/1/1/1, respectively. Median age (range) was 63 (58-81), and male/female was 4 /1. Four pts received at least 4 cycles of nivolumab, with a median cycle of 4 (1-15). According to RECIST ver1.1, one patient achieved PR, 2 pts showed SD and 2 pts had PD, corresponding to a disease control rate of 60%. The safety profile was equivalent to those in previous reports and no severe adverse reactions were seen. Conclusions: Nivolmab appeared to be beneficial and well-tolerated in pts with non-Sq. HNC and warrants further investigation for this rare disease subtype.

Exploratory analysis of prognostic factors for lenvatinib in radioiodine‐refractory differentiated thyroid cancer

Head & Neck

Case Reports in Oncology

Standard therapy for radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) is m... more Standard therapy for radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) is multi-targeted kinase inhibitors (m-TKIs), represented by sorafenib and lenvatinib. One of the main target molecules of m-TKIs is vascular endothelial growth factor receptor (VEGF-R). m-TKIs are known to cause adverse reactions such as hypertension and proteinuria as a class effect. In particular, proteinuria is thought to result from vascular endothelial damage and podocytopathy in glomeruli, and the development of thrombotic microangiopathy (TMA) has been reported for VEGF inhibitors. We encountered a patient with RAI-refractory (RR) papillary thyroid carcinoma (PTC) who developed proteinuria and renal dysfunction due to lenvatinib. Renal biopsy demonstrated that these changes were caused by TMA. To our knowledge, this is the first reported case of TMA due to lenvatinib in a Japanese patient with RR-PTC. A 70-year-old woman developed proteinuria, renal impairment and hypertension while ...

Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site

Journal of Clinical Oncology

PURPOSE Although gene expression profiling is a promising diagnostic technique to determine the t... more PURPOSE Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP. PATIENTS AND METHODS Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate. RESULTS One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in ...

Auris, nasus, larynx, 2018

Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory di... more Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib. She continued to receive lenvatinib but with repeated dose interruptions and reductions due to continuous proteinuria. Because of severe and persistent proteinuria as well as newly developed renal impairment, lenvatinib was suspended after two years of treatment. After the 7-month suspension, her proteinuria and renal impairment were partially improved, but her lung metastases progressed. Because she was unable to tolerate pre...

Oncotarget, Jan 6, 2018

The development of skin rashes is the most common adverse event observed in cancer patients treat... more The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm; = 0.009 in paired -test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm; = 0.028 in paired -test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, < 0.0001). Focal distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin r...

A phase I study for adjuvant chemotherapy of gemcitabine plus S-1 in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1202)

Cancer chemotherapy and pharmacology, 2018

To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected ... more To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy. A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1-14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level - 1), and 800/50 (Level - 2). Thirty-one patients (17 men and 14 women; median age, 70 years) were enrolled. Level 1 was chosen as the starting dose. Three of seven patients developed dose-limiting toxicities at Level 1 and the dose was de-escalated to Level - 1. Five of 12 patients developed Grade 4 neutropenia at Level - 1 and the dose was de-escalated to Level - 2. One patient developed Grade 4 neutropenia at Level - 2. Another patient was unable to receive the day 8 dose due to Grade 3 neutropenia at Level - 2. Level - 1 was confi...

O1-20-3A Prospective Study of the Efficacy of Influenza Vaccination for Cancer Patients Receiving Chemotherapy

Annals of Oncology, 2014

O1-6-4A Retrospective Analysis of Dacarbazine Monotherapy for Recurrent or Metastatic Mucosal Melanoma

Annals of Oncology, 2014

O1-4-1Relationship between Adverse Events and Efficacy of Lenvatinib for Thyroid Cancer

Annals of Oncology, 2016

International journal of hematology, 2017

Constitutional translocations that coincide with t(9;22)(q34;q11.2) may lead to unnecessary treat... more Constitutional translocations that coincide with t(9;22)(q34;q11.2) may lead to unnecessary treatments in chronic myeloid leukemia (CML) patients, as, under the standard criteria, a diagnosis of CML with additional chromosomal abnormalities indicates an accelerated phase (AP). In the present report, a 47-year-old male had pain in the right foot due to gout. Peripheral blood examination showed leukocytosis with left shift. Bone marrow aspiration revealed myeloid hyperplasia with megakaryocytosis. RT-PCR revealed the major BCR-ABL fusion transcript, and CML in the chronic phase was diagnosed, followed by nilotinib treatment. Although WBC counts decreased immediately, G-banding analysis showed 46,XY,t(8;22)(q24;q11.2),t(9;22)(q34;q11.2) [20]. The t(8;22)(q24;q11.2) translocation is known to be recurrent in Burkitt's lymphoma. The diagnosis was changed to CML in AP, leading to B-lymphoid crisis. Unexpectedly, the karyotype was 46,XY,t(8;22)(q24;q11.2) [20] in hematological complete ...

Anticancer Research, Jul 1, 2014

Aim: We evaluated the potential of TYRO3 as a therapeutic target in various types of breast cance... more Aim: We evaluated the potential of TYRO3 as a therapeutic target in various types of breast cancer cell lines. Materials and Methods: The effects of TYRO3-knockdown by small interfering RNA (siRNA) on proliferation, cell-cycle distribution, and cell signaling in four estrogen receptor (ER)-positive/HER2-non-amplified (luminal-type), two ERnegative/HER2-amplified (HER2-type), and two ERnegative/HER2-non-amplified (triple negative [TN]-type) cell lines were compared. Results: Whereas TYRO3 knockdown induced the greatest proliferation suppression in luminaltype cells, and to a lesser extent in HER2-type cells, no proliferation inhibition was observed in TN-type cells. The TYRO3 siRNA-induced proliferation inhibition in luminaltype cells was observed in both estradiol (E2)-rich and-null conditions. The proliferation suppression was correlated with G0-G1/S cell-cycle arrest. Western blot analysis showed a decrease in phosphorylation of ERK1/2 or STAT3, and in cyclin D1 only in cell lines sensitive to TYRO3-knockdown. Conclusion: TYRO3 is a potential therapeutic target in breast cancer, particularly in luminal-type cells.

Japanese Journal of Clinical Oncology, 2016

Objective: Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. ... more Objective: Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. Twodose vaccination is a proposed strategy for increasing vaccination efficacy; however, this has yet to be confirmed in this population. The purpose of this study was to clarify the efficacy and safety of this strategy. Methods: We conducted a multicentre prospective study on a two-dose vaccination regimen in cancer patients receiving chemotherapy. Second vaccinations were performed in patients who did not respond to all three viral strains after the first vaccination. Serum haemagglutination inhibition titres were measured to determine the patients' immunological response, 2 weeks prior to the first vaccination, 3-5 weeks after each vaccination, and at the end of the influenza season. Results: We enrolled 109 patients, including 70 with solid tumours, 36 with haematological malignancies, and 3 with both cancer types. Among the total patients, the proportion of patients with protective titres against the three viral strains increased significantly from 3 to 27% (P < 0.01) following vaccination. Among the 79 patients who received a second vaccination, the proportion of those with protective titres against the individual strains increased by 10% (H1N1), 8% (H3N2), and 3% (B) compared with after the first vaccination. Serious adverse events were not observed. Conclusions: We recommend influenza vaccinations for cancer patients, including those receiving chemotherapy. Also, the additional benefit of the second vaccination may be limited.