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1.
J Gastrointest Cancer ; 54(3): 951-961, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37037952

ABSTRACT

PURPOSE: Pembrolizumab demonstrated antitumor activity in programmed death ligand 1 positive (combined positive score (CPS) ≥ 1) gastric/gastroesophageal junction cancer in KEYNOTE-059 (third line or beyond), KEYNOTE-061 (second line), and KEYNOTE-062 (first line). We characterized efficacy and safety of pembrolizumab monotherapy in Japanese patients across several lines of therapy in these studies. METHODS: This analysis was conducted in 34 patients from KEYNOTE-059 cohort 1 (all pembrolizumab), including 13 patients with CPS ≥ 1, 65 patients with CPS ≥ 1 from KEYNOTE-061 (pembrolizumab, n = 27; chemotherapy, n = 38), and 70 patients with CPS ≥ 1 from KEYNOTE-062 (pembrolizumab, n = 38; chemotherapy, n = 32). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were evaluated. RESULTS: In KEYNOTE-059, ORR with pembrolizumab was 9%, median PFS was 2 months, and median OS was 10 months. In KEYNOTE-061, median OS was 12 months with pembrolizumab versus 10 months with chemotherapy (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.39-1.15). Median PFS (pembrolizumab vs. chemotherapy) was 2 months versus 4 months (HR, 1.21; 95% CI, 0.69-2.13); ORR was 7% versus 18%. In KEYNOTE-062, median OS was 20 months with pembrolizumab versus 18 months with chemotherapy (HR, 0.76; 95% CI, 0.43-1.33). Median PFS (pembrolizumab vs. chemotherapy) was 6 months versus 7 months (HR, 1.03; 95% CI, 0.61-1.74); ORR was 29% versus 34%. CONCLUSIONS: The current analysis provides valuable information that anti-PD-1 therapies are worthy of further assessment for gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02335411 (KEYNOTE-059), NCT02370498 (KEYNOTE-061), and NCT02494583 (KEYNOTE-062).


Subject(s)
Antibodies, Monoclonal, Humanized , Esophageal Neoplasms , Stomach Neoplasms , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , East Asian People , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Esophagogastric Junction/pathology , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy
2.
Rinsho Ketsueki ; 63(10): 1363-1372, 2022.
Article in Japanese | MEDLINE | ID: mdl-36351641

ABSTRACT

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Receptors, Chimeric Antigen , Humans , Receptors, Chimeric Antigen/therapeutic use , Retrospective Studies , Receptors, Antigen, T-Cell , Lymphoma, Large B-Cell, Diffuse/drug therapy , Immunotherapy, Adoptive/adverse effects , Antigens, CD19
3.
Cancer Sci ; 113(8): 2814-2827, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35701865

ABSTRACT

The KEYNOTE-659 study evaluated the efficacy and safety of first-line pembrolizumab plus S-1 and oxaliplatin (SOX) (cohort 1) or S-1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open-label phase IIb study enrolled patients with advanced programmed death-ligand 1 (PD-L1)-positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)-negative G/GEJ adenocarcinoma. The primary end-point was the objective response rate (ORR). Other end-points were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow-up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment-related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD-L1-positive, HER2-negative G/GEJ adenocarcinoma.


Subject(s)
Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , Stomach Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen/metabolism , Cisplatin/therapeutic use , Esophageal Neoplasms , Humans , Oxaliplatin/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology
4.
BMC Cancer ; 22(1): 640, 2022 Jun 11.
Article in English | MEDLINE | ID: mdl-35690729

ABSTRACT

BACKGROUND: Synchronous multiple primary malignant tumors (sMPMTs) are sometimes diagnosed in patients with malignant lymphoma. We herein investigated the prognostic impact of sMPMT in lymphoma patients and the optimal treatment strategy. METHODS: Seventy-five patients with sMPMTs (5.8%) among 1285 patients with lymphoma newly diagnosed between August 2004 and April 2020 were enrolled. RESULTS: In patients with indolent lymphoma, those with sMPMTs had a worse prognosis than those without sMPMTs (5-year overall survival [OS]: 73.4% and 87.8%, respectively; P = 0.047). Among those with high and low tumor burden, the cumulative rate of death due to solid tumors was significantly higher in patients with sMPMTs than those without sMPMTs (high tumor burden: 26.7% vs. 1.6%, P < 0.001; low tumor burden: 12.7% vs. 1.0%, P = 0.003). The presence of sMPMTs did not have a significant impact on outcomes in patients with diffuse large B-cell lymphoma (DLBCL) (5-year OS: 65.4% and 66.9%, respectively; P = 0.74; 5-year progression-free survival [PFS]: 65.5% and 59.9%, respectively; P = 0.65). However, the cumulative rate of death from solid tumor in patients with sMPMTs was significantly higher than in patients without sMPMTs (5-year cumulative rate: 7.4% and 2.1%, respectively; P = 0.004). The treatment sequence did not have a significant effect on outcomes or the relative dose intensity of chemotherapy. CONCLUSIONS: In patients with indolent lymphoma, those with sMPMTs had a significantly worse prognosis than those without sMPMTs, mainly because of high mortality due to solid tumors. The presence of sMPMTs was not a significant prognostic factor in patients with DLBCL. It is important to assess the status and need for early treatment of each type of malignancy in patients with sMPMTs.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Neoplasms, Multiple Primary , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Disease-Free Survival , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Neoplasms, Multiple Primary/drug therapy , Prognosis , Retrospective Studies , Rituximab/therapeutic use
5.
Medicine (Baltimore) ; 101(10): e29028, 2022 Mar 11.
Article in English | MEDLINE | ID: mdl-35451406

ABSTRACT

ABSTRACT: Maintaining relative dose intensity (RDI) of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Pegfilgrastim was approved in Japan in November 2014 to prevent febrile neutropenia (FN) and maintain RDI.In this retrospective study, we reviewed 334 patients with DLBCL who received 6 or more courses of R-CHOP and analyzed the differences in the RDI, overall survival (OS), and progression-free survival between patients whose treatment started after November 2014 (postapproval group) and those whose treatment started before October 2014 (pre-approval group).The incidence of FN was lower (20% vs 38.3%, P < .001) and the RDI of R-CHOP was higher (86.8% vs 67.8%, P < .001) in the postapproval group. Pegfilgrastim was administered to many of these patients (76.8%) and was thought to have contributed to the high RDI maintenance in the postapproval group. Interrupted time-series analysis showed a significant rise of the RDI at the timing of pegfilgrastim approval in patients aged <70 years (estimated change: 18.1%, P < .001). The 5-year OS (85.7% vs 69.9%, P = .009) and progression-free survival (81.4% vs 64.4%, P = .011) were superior in the postapproval group. However, the differences were not significant in matched-pair analysis matching National Comprehensive Cancer Network-International Prognostic Index scores. Improved survival outcomes in this group were observed only among patients with Ann Arbor stage 3/4 (5-year OS: 83.7% vs 61.3%, P = .019) and high-risk on the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 80.7% vs 32.4%, P = .014). Multivariate analysis showed that a high RDI and low lactate dehydrogenase were associated with superior OS (RDI ≥ 85%, hazard ratio: 0.48, P = .016; lactate dehydrogenase > institutional upper limit of normal, hazard ratio: 2.38, P = .005).The RDI of R-CHOP was able to be maintained at higher levels, the incidence of FN was lower, and significantly better clinical outcomes were achieved in clinically high-risk groups after pegfilgrastim approval. Maintaining a high RDI in R-CHOP by administering pegfilgrastim to those who are likely to have low RDI without it is important for achieving favorable outcomes in patients with DLBCL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Large B-Cell, Diffuse , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Filgrastim , Humans , Lactate Dehydrogenases , Polyethylene Glycols , Prednisone/therapeutic use , Retrospective Studies , Rituximab/therapeutic use , Vincristine/therapeutic use
6.
Commun Biol ; 5(1): 20, 2022 01 11.
Article in English | MEDLINE | ID: mdl-35017627

ABSTRACT

Transcriptome analysis of circulating tumor cells (CTCs), which migrate into blood vessels from primary tumor tissues, at the single-cell level offers critical insights into the biology of metastasis and contributes to drug discovery. However, transcriptome analysis of single CTCs has only been reported for a limited number of cancer types, such as multiple myeloma, breast, hepatocellular, and prostate cancer. Herein, we report the transcriptome analysis of gastric cancer single-CTCs. We utilized an antigen-independent strategy for CTC isolation from metastatic gastric cancer patients involving a size-dependent recovery of CTCs and a single cell isolation technique. The transcriptomic profile of single-CTCs revealed that a majority of gastric CTCs had undergone epithelial-mesenchymal transition (EMT), and indicated the contribution of platelet adhesion toward EMT progression and acquisition of chemoresistance. Taken together, this study serves to employ CTC characterization to elucidate the mechanisms of chemoresistance and metastasis in gastric cancer.


Subject(s)
Neoplastic Cells, Circulating , Stomach Neoplasms , Transcriptome/genetics , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Humans , Neoplastic Cells, Circulating/metabolism , Neoplastic Cells, Circulating/pathology , Single-Cell Analysis , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology
7.
Medicine (Baltimore) ; 100(44): e27733, 2021 Nov 05.
Article in English | MEDLINE | ID: mdl-34871273

ABSTRACT

RATIONALE: Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy. PATIENTS CONCERNS: We report a case of a 61-year-old, male patient with intravascular large B-cell lymphoma who suffered a CNS relapse after standard chemotherapy. DIAGNOSIS: A diagnosis of intravascular large B-cell lymphoma with CNS involvement was made. INTERVENTIONS: We treated the patient using CAR T-cell therapy following a conditioning regimen consisting of thiotepa and busulfan and autologous stem cell transplantation. Although he experienced grade 1 cytokine release syndrome, no other serious adverse events, such as immune effector cell-associated neurotoxicity syndrome or pseudoprogression, were observed. OUTCOMES: The patient achieved complete remission after the CAR T-cell infusion. LESSONS: CAR T-cell therapy following autologous stem cell transplantation is a viable option for relapsed/refractory lymphoma with CNS infiltration. Further clinical studies are warranted to verify its safety and efficacy.


Subject(s)
Central Nervous System Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive/methods , Lymphoma, Large B-Cell, Diffuse/therapy , Neoplasms, Second Primary/therapy , Neurotoxicity Syndromes , Receptors, Chimeric Antigen , Transplantation, Autologous/adverse effects , Central Nervous System , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Receptors, Antigen, T-Cell
8.
Jpn J Clin Oncol ; 51(6): 879-885, 2021 May 28.
Article in English | MEDLINE | ID: mdl-33561262

ABSTRACT

OBJECTIVE: We evaluated the efficacy and safety of first-line S-1 plus cisplatin in combination with cetuximab for Japanese patients with advanced gastric cancer, including gastroesophageal junction adenocarcinoma. METHODS: This open-label, single arm, multicenter, phase 2 trial was conducted to assess first-line cetuximab plus S-1 plus cisplatin for advanced gastric cancer. A total of 40 patients from 10 centers were enrolled. Cetuximab was administered weekly, with the initial infusion at 400 mg/m2 and then 250 mg/m2 each subsequent week. S-1 plus cisplatin chemotherapy was concomitantly conducted in a 5-week cycle: S-1 (40-60 mg, adjusted for body surface area) was given twice daily for 3 consecutive weeks, followed by a 2-week rest period, and cisplatin (60 mg/m2) was given on day 8 of each cycle for a maximum of 8 cycles. Treatment continued until the occurrence of radiographically confirmed progressive disease, unacceptable toxicity or withdrawal of consent. The primary endpoint was the best overall response. Secondary endpoints included progression-free survival and safety. RESULTS: A total of 40 patients were evaluable. One patient (2.5%) had a complete response; 15 patients (37.5%) had a partial response. The observed overall response rate according to the independent review committee was 40.0% (95% confidence interval, 24.9-56.7; P = 0.7043 [one-sided null hypothesis: overall response rate ≤ 43%]); median PFS was 5.6 months (95% confidence intervals, 4.2-8.3). No adverse events leading to death were reported during the study, and no specific safety concerns were observed. CONCLUSIONS: Overall, the addition of cetuximab to S-1 plus cisplatin was well tolerated in patients with advanced gastric cancer but provided no additional clinical benefit in this study. ClinicalTrials.gov identifier: NCT01388790.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cetuximab/administration & dosage , Cisplatin/administration & dosage , Oxonic Acid/administration & dosage , Stomach Neoplasms/drug therapy , Tegafur/administration & dosage , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Cetuximab/adverse effects , Cetuximab/therapeutic use , Cisplatin/adverse effects , Drug Administration Schedule , Drug Combinations , Female , Humans , Japan/epidemiology , Male , Middle Aged , Oxonic Acid/adverse effects , Remission Induction , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Tegafur/adverse effects , Treatment Outcome
9.
Clin Drug Investig ; 41(1): 53-64, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33355909

ABSTRACT

BACKGROUND AND OBJECTIVE: Gastric cancer has been associated with notable geographic heterogeneity in previous multi-regional studies. In particular, patients from Japan have better outcomes compared with patients from other regions. Here, we assess patient-focused outcomes for the subgroup of Japanese patients in the global RAINBOW study. METHODS: Quality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) at baseline and 6-week intervals. Investigators assessed performance status before each 4-week cycle. Time-to-deterioration in each QLQ-C30 scale was defined as randomization to first worsening of ≥ 10 points (on a 100-point scale). Time-to-deterioration in performance status was defined as first worsening to ≥ 2. Hazard ratios were estimated using Cox proportional hazards models. RESULTS: The Japan subgroup contained 140 patients (ramucirumab plus paclitaxel, n = 68; placebo plus paclitaxel, n = 72); baseline QoL data were available for all patients. At baseline, QLQ-C30 scores were similar between study arms. Of the 15 QLQ-C30 scales, nine had a hazard ratio < 1, indicating similar or numerically longer time-to-deterioration in QoL for ramucirumab plus paclitaxel; all 95% confidence intervals included 1. Best mean change from baseline numerically favored ramucirumab plus paclitaxel in most QoL scales. The hazard ratios for time-to-deterioration of performance status to ≥ 2 were 0.64 in the Japan subgroup and 0.88 in the non-Asian subgroup. The Japan subgroup had better QoL at baseline compared with the non-Asian subgroup. CONCLUSIONS: Treatment with ramucirumab plus paclitaxel maintained QoL and performance status over time compared with placebo plus paclitaxel in the Japan subgroup of the RAINBOW trial. These data suggest that the heterogeneity in gastric cancer between geographic regions includes multiple measures of QoL. TRIAL REGISTRATION NUMBER: NCT01170663 (first submitted 21 July, 2010).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Quality of Life , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Double-Blind Method , Female , Humans , Japan , Male , Middle Aged , Paclitaxel/administration & dosage , Young Adult , Ramucirumab
10.
Int J Clin Oncol ; 26(3): 485-493, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33225396

ABSTRACT

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of coronavirus disease 2019 (COVID-19), data on the clinical characteristics of COVID-19 patients with cancer are limited. This study aimed to evaluate the clinical characteristics and outcomes including mortality and viral shedding period in COVID-19 patients with cancer in Japan. METHODS: We retrospectively analyzed 32 patients with a history of cancer who were referred to our hospital between January 31, 2020 and May 25, 2020. We evaluated the association between clinical outcomes and potential prognostic factors using univariate analyses. RESULTS: The median age was 74.5 (range 24-90) years and 22 patients (69%) were men. A total of 11 patients (34%) died. Our analyses demonstrated that the mortality was significantly associated with lymphocyte count, albumin, lactate dehydrogenase, serum ferritin, and C-reactive protein on admission. The median period between illness onset and the first effective negative SARS-CoV-2 PCR result was 22 days (interquartile range 18-25) in survivors. Of four patients with hematological malignancy who developed COVID-19 within the rest period of chemotherapy, three died and the other patient, who received bendamustine plus rituximab therapy, had the longest duration of viral shedding (56 days). CONCLUSION: Our study suggested that the risk factors for mortality previously reported in general COVID-19 patients, including lymphocytopenia, were also effective in cancer patients. Patients who received cytotoxic chemotherapy recently or were treated with chemotherapy, which can lead to lymphocyte reduction, had poor prognosis and prolonged periods of viral shedding.


Subject(s)
COVID-19 , Neoplasms , Adult , Aged , Aged, 80 and over , China , Humans , Japan/epidemiology , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Tokyo , Young Adult
11.
Gan To Kagaku Ryoho ; 47(8): 1205-1208, 2020 Aug.
Article in Japanese | MEDLINE | ID: mdl-32829355

ABSTRACT

Standard regimens for extrapulmonary neuroendocrine carcinomas(EPNEC)are not established. Treatment used for small cell lung cancer is also used for EPNECs. Amrubicin(AMR) monotherapy is used as salvage therapy for small cell lung cancer, but its efficacy in EPNEC is not clear. The aim of this study was to estimate the efficacy of AMR monotherapy in EPNEC. We retrospectively investigated patients with EPNEC who received first-line platinum-based chemotherapy between April 2007 and March 2019. The time to treatment failure(TTF)and the efficacy and toxicity was analyzed in the patients who received AMR monotherapy. Among 43 patients with EPNEC, 14(13 males, one female; median age, 58 years)received AMR monotherapy. Primary site included the pancreas(n=3), stomach(n=3), rectum(n=1), anal canal(n=1), salivary glands(n= 1), urothelial(n=1), bladder(n=1), prostate(n=1), and 2 patients had primary unknown cancer. Pathological type included small cell(n=4), large cell(n=2), and other types(n=8). Prior chemotherapy comprised CDDP plus CPT-11(n =5), CDDP plus ETP(n=2), and CBDCA plus ETP(n=6). The median TTF was 49(20-61)days. One patient had a partial response and the disease control rate was 33%. The common adverse events of >Grade 3 were leukopenia(69%), neutropenia(62%), and febrile neutropenia(23%). AMR monotherapy was clinically effective and safe for EPNEC.


Subject(s)
Anthracyclines/therapeutic use , Carcinoma, Neuroendocrine , Antineoplastic Agents , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Neuroendocrine/drug therapy , Female , Humans , Lung Neoplasms , Male , Middle Aged , Platinum , Retrospective Studies , Treatment Outcome
12.
Oxf Med Case Reports ; 2020(6): omaa040, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32617167

ABSTRACT

A 46-year-old female patient with glioblastoma multiforme (GBM), IDH wild type developed severe pancytopenia 5 months after postoperative chemoradiotherapy. Bone marrow aspirate showed normocellular marrow with 70.0% abnormal cells, which suggested the possibility of acute myeloid leukemia. Immunophenotypic analysis did not show any hematological lineage markers, except for cluster of differentiation 56. The results of immunohistochemical staining of glial fibrillary acidic protein and oligodendrocyte transcription Factor 2 were positive. Based on these findings, the patient was diagnosed with bone marrow metastasis from GBM. Bone marrow metastasis from GBM is rare and little is known about the morphological characteristics of bone marrow aspiration smear findings. We experienced a rare case with marrow metastasis from GBM mimicking acute myeloid leukemia.

13.
Gan To Kagaku Ryoho ; 47(1): 49-53, 2020 Jan.
Article in Japanese | MEDLINE | ID: mdl-32381862

ABSTRACT

FOLFOX therapy has been used for gastric cancer in Japan since 2017. We retrospectively analyzed the efficacy of FOLFOX therapy compared to that of FP. Forty-seven cases were evaluated between January 2010 and December 2018. Eighteen patients received mFOLFOX6 therapy, and 29 patients received FP therapy. The median time to treatment failure was 206 days in the mFOLFOX6 group and 58 days in the FP group. The response rate was 50% in the mFOLFOX6 group and 17% in the FP group. Neutropenia(56%), thrombocytopenia(50%), and peripheral neuropathy(56%)were the common adverse events in the mFOLFOX6 group, and leukopenia(69%)and neutropenia(69%)were the common adverse effects in the FP group. Based on our results, we conclude that, unlike FP, FOLFOX is an effective therapy for of gastric cancer.


Subject(s)
Stomach Neoplasms , Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Fluorouracil , Humans , Japan , Leucovorin , Organoplatinum Compounds , Retrospective Studies , Treatment Outcome
14.
Eur J Cancer ; 129: 97-106, 2020 04.
Article in English | MEDLINE | ID: mdl-32145474

ABSTRACT

AIM: The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab). METHODS: This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status. RESULTS: Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%). CONCLUSIONS: SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer. TRIAL REGISTRATION: NCT03382600/JapicCTI-183829.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , B7-H1 Antigen/analysis , Esophageal Neoplasms/drug therapy , Esophagogastric Junction/pathology , Stomach Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , Drug Combinations , Esophageal Neoplasms/immunology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagogastric Junction/immunology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Oxaliplatin/administration & dosage , Oxaliplatin/adverse effects , Oxonic Acid/administration & dosage , Oxonic Acid/adverse effects , Progression-Free Survival , Receptor, ErbB-2/analysis , Receptor, ErbB-2/metabolism , Remission Induction/methods , Stomach Neoplasms/immunology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Tegafur/administration & dosage , Tegafur/adverse effects
15.
Hematol Oncol ; 38(3): 309-317, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32223021

ABSTRACT

The controlling nutritional status (CONUT) score is a nutritional index calculated from serum albumin and total cholesterol levels and lymphocyte counts. Its role in predicting clinical outcomes of diffuse large B-cell lymphoma (DLBCL) has not been evaluated. In this retrospective study, data from 476 patients with DLBCL were analyzed. The cutoff value of the CONUT score was set as 4. CONUT score significantly stratified the overall survival (OS) and the progression-free-survival (PFS) (5-year OS, 49.0% vs 83.2%, P < .001; 5-year PFS, 46.1% vs 73.1%, P < .001) of the patients. Among patients at high-intermediate or high risk, as per the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), 5-year OS was lower in patients with high CONUT scores than in those with low CONUT scores (high-intermediate risk, 51.2% vs 75.5%, P < .001; high risk, 29.9% vs 63.3%, P = .007). Additionally, in patients with high CONUT scores, maintenance of relative dose intensity (RDI) of chemotherapy did not affect the 5-year OS (RDI > 80% vs RDI ≤ 80%: 59.8% vs 50.9%, P = .73). In the present study, we have demonstrated that the CONUT score is an independent prognostic factor in patients with DLBCL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/mortality , Nutrition Assessment , Nutritional Status , Adult , Aged , Aged, 80 and over , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Predictive Value of Tests , Prednisone/administration & dosage , Retrospective Studies , Rituximab/administration & dosage , Survival Rate , Vincristine/administration & dosage
16.
Asia Pac J Clin Oncol ; 16(1): 5-13, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31721447

ABSTRACT

AIM: The phase II/III GATSBY study (NCT01641939) showed that trastuzumab emtansine did not have an efficacy benefit over taxane in patients with previously treated, human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic gastric or gastroesophageal junction cancer. We evaluated patients from Japanese centers within GATSBY. METHODS: In stage one, patients (randomized 2:2:1) received trastuzumab emtansine 3.6 mg/kg every 3 weeks, trastuzumab emtansine 2.4 mg/kg weekly, or physician's choice of taxane (docetaxel 75 mg/m² every 3 weeks or paclitaxel 80 mg/m² weekly). In stage two, patients (randomized 2:1) received trastuzumab emtansine 2.4 mg/kg weekly or taxane. Eligible patients had centrally assessed HER2-positive disease and progression during or after first-line therapy. Primary endpoint was overall survival. We present the 2.4 mg/kg weekly data. RESULTS: Eighty-two patients were randomized (intention-to-treat: 48 to trastuzumab emtansine 2.4 mg/kg weekly, 23 to taxane; September 2012-August 2014) at 19 sites. Median overall survival was 11.8 months (95% confidence interval [CI], 9.3-16.3) with trastuzumab emtansine 2.4 mg/kg weekly and 10.0 months (95% CI, 7.1-18.2) with taxane (unstratified hazard ratio = 0.94, 95% CI, 0.52-1.72). Trastuzumab emtansine 2.4 mg/kg weekly, versus taxane, was associated with fewer grade ≥3 adverse events (AEs; 52.1% vs 68.2%) and serious AEs (14.6% vs 18.2%). There were no fatal AEs. CONCLUSIONS: Efficacy in Japanese patients within GATSBY was consistent with the overall population; overall survival was not prolonged with trastuzumab emtansine 2.4 mg/kg weekly versus taxane. The safety profile of trastuzumab emtansine was similar to the overall population.


Subject(s)
Adenocarcinoma/drug therapy , Ado-Trastuzumab Emtansine/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Esophagogastric Junction/drug effects , Receptor, ErbB-2/metabolism , Salvage Therapy , Stomach Neoplasms/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Adult , Aged , Esophagogastric Junction/metabolism , Esophagogastric Junction/pathology , Female , Humans , Japan , Male , Middle Aged , Prognosis , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Survival Rate , Young Adult
17.
Case Rep Oncol ; 12(2): 657-665, 2019.
Article in English | MEDLINE | ID: mdl-31572155

ABSTRACT

Fluorouracil plus oxaliplatin (L-OHP) (FOLFOX) plus bevacizumab (BV) therapy is commonly administered to patients with metastatic colorectal cancer. However, few reports have described L-OHP therapy in hemodialysis patients, and the efficacy and safety remain uncertain in this population. Here, we report three cases of hemodialysis patients with colorectal cancer who received a modified FOLFOX-6 (mFOLFOX-6, or FOLFOX plus folinic acid) plus BV regimen every 3 weeks. One patient, a 65-year-old man with chronic renal failure consequent to diabetic nephropathy, underwent hemodialysis 3 times/week. He exhibited a partial response after 7 cycles of mFOLFOX-6 plus BV, with the major adverse events of Grade 1 peripheral neuropathy and Grade 2 thrombocytopenia. He died of perforation-related septic shock. A 71-year-old man previously treated with bosutinib for chronic myelocytic leukemia received 9 cycles of mFOLFOX-6 plus BV and achieved stable disease. Chemotherapy was administered every 4 weeks, and the 5-fluorouracil dose was reduced after he developed Grade 4 neutropenia. A 71-year-old woman with chronic renal failure consequent to diabetic nephropathy underwent hemodialysis 3 times a week. She received 3 cycles of mFOLFOX-6 plus BV, but exhibited disease progression and developed Grade 4 neutropenia, which necessitated a reduced 5-fluorouracil dose. After completing FOLFOX therapy, she began second-line irinotecan/5-fluorouracil/leucovorin (FOLFIRI) plus BV therapy. In two cases, bone marrow suppression increased the difficulty of L-OHP dose escalation. We conclude that mFOLFOX-6 plus BV, with appropriate dose reduction, is acceptable for patients with chronic renal failure. Further data are needed to determine the adequate chemotherapy dose.

18.
JAMA Netw Open ; 2(8): e198243, 2019 08 02.
Article in English | MEDLINE | ID: mdl-31373648

ABSTRACT

Importance: Ramucirumab, a human IgG 1 antibody against vascular endothelial growth factor receptor 2, has been shown to improve progression-free survival and overall survival in patients with advanced gastric cancer in the second-line setting. Objective: To compare progression-free survival for S-1 and oxaliplatin plus ramucirumab with that for S-1 and oxaliplatin plus placebo in patients with advanced gastric cancer. Design, Setting, and Participants: This phase 2, double-blind randomized clinical trial (RAINSTORM [First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab in Patients With Advanced Gastric Cancer]) was conducted from October 12, 2015, to April 11, 2018, at 36 sites in Japan, South Korea, and Taiwan. Participants were chemotherapy-naive patients (n = 189) with metastatic gastric or gastroesophageal adenocarcinoma. Analyses of the full analysis set and safety population were conducted between November 27, 2017, and June 4, 2018. Interventions: Patients randomized to the ramucirumab plus S-1 and oxaliplatin arm received S-1, 80 to 120 mg/d twice daily, on days 1 to 14 and oxaliplatin, 100 mg/m2, on day 1 with ramucirumab, 8 mg/kg, on days 1 and 8 in part A (21-day cycle). Patients randomized to the placebo plus S-1 and oxaliplatin arm received the same S-1 and oxaliplatin dosage as well as placebo on days 1 and 8 in part A. Eligible patients received second-line paclitaxel, 80 mg/m2, on days 1, 8, and 15 and ramucirumab, 8 mg/kg, on days 1 and 15 in part B (28-day cycle). Main Outcomes and Measures: The primary end point was progression-free survival, analyzed using the stratified log-rank test; the hazard ratio (HR) was estimated using the stratified Cox proportional hazards regression model. Secondary end points included overall survival and adverse events. Results: In total, 189 patients were randomized and received treatment: 96 to the ramucirumab plus S-1 and oxaliplatin arm and 93 to the placebo plus S-1 and oxaliplatin arm. Among the 189 patients, 121 (64.0%) were male, and the median (range) age was 62.0 (26-84) years. Median progression-free survival was not prolonged in the ramucirumab plus S-1 and oxaliplatin arm compared with the placebo plus S-1 and oxaliplatin arm (6.34 [80% CI, 5.65-6.93] vs 6.74 [80% CI, 5.75-7.13] months; HR, 1.07; 80% CI, 0.86-1.33; P = .70). Median overall survival was 14.65 (80% CI, 12.39-15.67) months in the ramucirumab plus S-1 and oxaliplatin arm and 14.26 (80% CI, 13.83-17.31) months in the placebo plus S-1 and oxaliplatin arm (HR, 1.11; 80% CI, 0.89-1.40; P = .55). The most commonly reported grade 3 or higher treatment-emergent adverse events in the ramucirumab plus S-1 and oxaliplatin arm in part A were decreased neutrophil count (14 patients [14.6%]), hypertension (10 patients [10.4%]), and anemia (10 patients [10.4%]). Conclusions and Relevance: In this randomized clinical trial, the addition of ramucirumab to first-line S-1 and oxaliplatin treatment did not prolong progression-free survival or overall survival compared with S-1 and oxaliplatin alone among East Asian patients with advanced gastric cancer; no new safety signals for ramucirumab were identified. Trial Registration: ClinicalTrials.gov identifier: NCT02539225.


Subject(s)
Adenocarcinoma/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Agents/therapeutic use , Oxaliplatin/therapeutic use , Paclitaxel/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asia , Double-Blind Method , Female , Humans , Male , Middle Aged , Ramucirumab
19.
Intern Med ; 58(20): 2957-2962, 2019 Oct 15.
Article in English | MEDLINE | ID: mdl-31243233

ABSTRACT

Gemcitabine plus nab-paclitaxel is the current standard chemotherapy for patients with metastatic pancreatic cancer. We conducted a phase I/II study in Japan, in which high response rates and manageable toxicity were observed. In this study, two patients were reported as experiencing pancreatitis due to chemotherapy. In general, pancreatitis is sometimes observed when the tumor involves the pancreatic duct, and the onset is observed before the diagnosis or at the initial stage. The onset of pancreatitis in these cases was unique and observed after the start of chemotherapy. Pancreatitis may be induced by the alleviation of stenosis of the pancreatic duct associated with tumor shrinkage.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/secondary , Pancreatic Neoplasms/drug therapy , Pancreatitis/chemically induced , Acute Disease , Aged , Albumins/administration & dosage , Albumins/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Pancreatic Ductal/diagnostic imaging , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Pancreatitis/diagnostic imaging , Tomography, X-Ray Computed , Gemcitabine
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