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1.
J Gastrointest Oncol ; 14(2): 676-691, 2023 Apr 29.
Article in English | MEDLINE | ID: mdl-37201044

ABSTRACT

Background: Little is known about the biweekly combined use of cetuximab and chemotherapy as second-line treatment of metastatic colorectal cancer (mCRC). Recently, DNA methylation status has been reported to be a new possible predictor of the efficacy from the anti-epidermal growth factor receptor (EGFR) antibody treatment. The purpose of this study was to examine the efficacy and safety of biweekly cetuximab plus mFOLFOX6 or mFOLFIRI as a second-line treatment for KRAS exon 2 wild-type mCRC. We also investigated the predictability of DNA methylation status on the efficacy of the EGFR antibody-containing treatment. Methods: Patients who were refractory or intolerant to the first-line chemotherapy were enrolled and received biweekly cetuximab plus mFOLFOX6 or mFOLFIRI. The primary endpoint was progression-free survival (PFS). Tumor evaluations were performed every 2 months using Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. DNA methylation status of colorectal cancer cells was defined by a modified MethyLight assay. Results: Sixty-six cases were enrolled. The median PFS (mPFS) was 5.1 [95% confidence interval (CI), 3.8-7.6] months. The median overall survival (mOS) was 12.7 (95% CI, 7.5-15.3) months. Grade 3 or higher neutropenia occurred in 53.0% of patients, whereas skin disorders with a grade 3 or higher occurred in <15% of patients. In multivariate analysis, DNA methylation status could not be an independent predictor of PFS [hazard ratio (HR), 1.43; P=0.39] and OS (HR, 2.13; P=0.086). However, in RAS/BRAF wild-type patients, the mPFS and mOS in the low-methylated colorectal cancer (LMCC) group was numerically better than those in the highly-methylated colorectal cancer (HMCC) group, although the difference was not statistically significant [mPFS: 8.5 (95% CI, 6.1-10.9) vs. 3.3 (95% CI, 1.2-not reached) months, P=0.79; ΔmPFS, 5.2 months; mOS: 15.3 (95% CI, 11.9-23.5) vs. 6.5 (95% CI, 3.1-not reached) months, P=0.53; ΔmOS, 8.8 months]. Conclusions: Biweekly cetuximab plus mFOLFOX6 or mFOLFIRI is a useful second-line therapy for mCRC. DNA methylation status warrants further exploration as a predictive biomarker for anti-EGFR efficacy in mCRC.

2.
Tohoku J Exp Med ; 254(1): 49-55, 2021 05.
Article in English | MEDLINE | ID: mdl-34053967

ABSTRACT

Whether trastuzumab use beyond disease progression is beneficial in second-line treatment for patients with unresectable human epidermal growth factor receptor 2 (HER2)-positive gastric cancer remains to be elucidated. We conducted this phase II study to assess whether trastuzumab plus docetaxel was effective for patients with previously treated advanced HER2-positive gastric cancer. This trial was a single-arm, open-label, multicenter, phase II study, conducted by Tohoku Clinical Oncology Research and Education Society (T-CORE). Patients aged 20 years or older who had advanced HER2-positive gastric cancer and were refractory to trastuzumab, fluoropyrimidine, and cisplatin were enrolled. Patients were treated with 6 mg/kg trastuzumab and 60 mg/m2 docetaxel every 3 weeks. The primary endpoint was the overall response rate. The threshold overall response rate was estimated to be at 15%. Secondary endpoints were progression-free survival, 6-month survival rate, overall survival, and toxicities. A total of 27 patients were enrolled from 7 hospitals. The median age was 67 years. Partial response was seen in 3 patients among the 26 evaluated patients. The overall response rate was at 11.5% (90% confidence interval 1.2%-21.8%). The median progression-free survival was 3.2 months, the 6-month survival rate was 85%, and the median overall survival was 11.6 months. Febrile neutropenia was observed in 14.8%. The most frequently observed grade 3 non-hematologic toxicity was anorexia (14.8%). The primary endpoint was not achieved. The results support a current consensus that the continuation of trastuzumab in second-line therapy for gastric cancer is not a recommended option.


Subject(s)
Breast Neoplasms , Stomach Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Docetaxel/therapeutic use , Female , Humans , Progression-Free Survival , Stomach Neoplasms/drug therapy , Trastuzumab/therapeutic use
3.
BMC Cancer ; 21(1): 116, 2021 Feb 04.
Article in English | MEDLINE | ID: mdl-33541293

ABSTRACT

BACKGROUND: Irinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC. METHODS: This meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: Nineteen trials involving 4571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82-0.98, P = 0.02), but not with OS (pooled HR = 0.91, 95% CI = 0.80-1.03, P = 0.15). CONCLUSION: Although the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. The combination of anti-VEGF antibody and IRI was associated with better PFS compared with anti-VEGF antibody and Ox. Both regimens could be used as the first-line treatments for mCRC with consideration of the patients' condition or toxicity profiles.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Humans , Irinotecan/administration & dosage , Oxaliplatin/administration & dosage , Prognosis , Systematic Reviews as Topic
4.
Future Oncol ; 17(8): 869-875, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32954810

ABSTRACT

Nivolumab is an increasingly used standard care treatment for heavily pretreated patients with advanced gastric cancer, with increasing clinical use in Japan. Data from retrospective studies on various tumors have shown the objective response rate to cytotoxic chemotherapy potentially improves after an exposure to immune checkpoint inhibitors. Based on these data, we conducted the multicenter observational REVIVE study to evaluate the efficacy and safety of cytotoxic chemotherapy in nivolumab-refractory or nivolumab-intolerant patients with advanced gastric cancer. Patients who are refractory or intolerant to nivolumab and scheduled to receive irinotecan monotherapy, oxaliplatin combination treatment or oral trifluridine/tipiracil hydrochloride therapy will be included. The primary end point is overall survival of nivolumab-pretreated patients with advanced gastric cancer after the cytotoxic chemotherapy. Clinical trial registration: UMIN000032182 (umin.ac.jp).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Nivolumab/pharmacology , Stomach Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Combinations , Drug Resistance, Neoplasm , Humans , Irinotecan/pharmacology , Irinotecan/therapeutic use , Japan/epidemiology , Multicenter Studies as Topic , Neoplasm Staging , Nivolumab/therapeutic use , Observational Studies as Topic , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Progression-Free Survival , Prospective Studies , Pyrrolidines/pharmacology , Pyrrolidines/therapeutic use , Stomach Neoplasms/diagnosis , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Thymine/pharmacology , Thymine/therapeutic use , Trifluridine/pharmacology , Trifluridine/therapeutic use
5.
BMC Cancer ; 20(1): 338, 2020 Apr 21.
Article in English | MEDLINE | ID: mdl-32316940

ABSTRACT

BACKGROUND: Ramucirumab monotherapy as a second-line treatment for advanced gastric cancer (AGC) prolongs survival compared to the best supportive care. However, in clinical practice, ramucirumab monotherapy is sometimes used as third- or later-line treatment for AGC refractory to fluoropyrimidine and taxanes. This study evaluated the efficacy and safety of salvage-line ramucirumab monotherapy for treating AGC. METHODS: The subjects of this retrospective study were advanced gastric or gastro-esophageal junction adenocarcinoma patients who received ramucirumab monotherapy after failure of 2 or more prior regimens containing fluoropyrimidine and taxanes but not ramucirumab. RESULTS: From June 2015 to April 2017, 51 patients were enrolled. The median progression-free survival (PFS) and overall survival (OS) were 1.8 (95% confidence interval [CI] = 1.6-2.2) and 5.1 (95% CI = 4.0-6.8) months, respectively. The objective response and disease control rates were 2 and 17%, respectively. Grade 3 adverse events (AEs; e.g., anemia, fatigue, hypertension, proteinuria, intestinal bleeding) occurred in seven (13%) patients, but no grade 4 AEs and treatment-related deaths were observed. A neutrophil-lymphocyte ratio (NLR) of < 2.5 and previous gastrectomy were associated with better PFS. CONCLUSIONS: Salvage-line ramucirumab monotherapy has acceptable toxicity and comparable efficacy to second-line treatment; therefore, we consider physicians might choose this therapy as a salvage-line treatment option for AGC refractory to the standard therapies.


Subject(s)
Adenocarcinoma/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Esophagogastric Junction/drug effects , Salvage Therapy , Stomach Neoplasms/drug therapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Esophagogastric Junction/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology , Survival Rate , Ramucirumab
6.
Int J Clin Oncol ; 25(2): 258-266, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31620932

ABSTRACT

BACKGROUND: Prophylactic percutaneous endoscopic gastrostomy (PEG) has been widely performed before concurrent chemoradiotherapy (CCRT) for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) because severe oral mucositis and dysphagia induced by CCRT lead to difficulty with oral intake. However, it is controversial whether all patients require prophylactic PEG for adjuvant CCRT. This study evaluated predictive factors for the feasibility of oral intake in adjuvant CCRT for patients with LASCCHN. METHODS: This study retrospectively analyzed 117 LASCCHN patients who underwent surgery followed by adjuvant CCRT with cisplatin at Shizuoka Cancer Center between April 2008 and December 2018. To investigate predictive factors for the feasibility of oral intake, tumor factors, treatment factors and social factors were included in multivariate analyses. RESULTS: Of the 117 patients, 25 received total laryngectomy and 92 received other surgery. In multivariate analysis, total laryngectomy [HR (hazard ratio) 0.09, P = 0.001] and oral cavity of primary tumor location (HR 0.21, P = 0.031) were significantly associated with the feasibility of oral intake. Difficulty obtaining adequate nutrition via oral intake from initiation of CCRT until 1 year after its completion was significantly rarer in the total laryngectomy group than in the other surgery group (16% vs. 57%, P < 0.001). CONCLUSION: Our study suggests that majority of patients who underwent total laryngectomy are able to maintain oral intake during adjuvant chemoradiotherapy.


Subject(s)
Chemoradiotherapy, Adjuvant , Gastroscopy/methods , Gastrostomy/methods , Head and Neck Neoplasms/therapy , Squamous Cell Carcinoma of Head and Neck/therapy , Administration, Oral , Adult , Aged , Antineoplastic Agents/administration & dosage , Chemoradiotherapy, Adjuvant/adverse effects , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Deglutition Disorders/etiology , Feasibility Studies , Female , Head and Neck Neoplasms/surgery , Humans , Laryngectomy , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/surgery
7.
Clin Colorectal Cancer ; 19(1): 13-21.e3, 2020 03.
Article in English | MEDLINE | ID: mdl-31732439

ABSTRACT

BACKGROUND: Regorafenib demonstrated survival benefits as salvage therapy for patients with metastatic colorectal cancer. However, severe toxicities frequently occurred early in the treatment with the standard dose (160 mg/day), resulting in a dose reduction or interruption. To improve the tolerability and maintain sufficient efficacy, we conducted a phase II study of regorafenib with a lower starting dose (120 mg/day). PATIENTS AND METHODS: Regorafenib was initiated at 120 mg/day, and the dosage was increased to 160 mg/day on day 15 of the first cycle for patients who had met the dose escalation criteria. The primary endpoint was the disease control rate (DCR). The pharmacokinetics of the total and unbound regorafenib and its active metabolites (M2, M5) were assessed. RESULTS: A total of 70 patients were enrolled from September 2016 to December 2017. Only 6 patients achieved dose escalation to 160 mg on day 15 as planned. For the 68 evaluable patients, the DCR was 32.4% (95% confidence interval, 21.5%-44.8%), which was less than the threshold (30%) of our statistical hypothesis. The serum concentrations of total regorafenib for patients whose dose was escalated to 160 mg/day were significantly lower than those of the patients whose dose was not escalated (median, 3978 vs. 7244 nM; P = .027). The serum unbound concentrations of the sum of regorafenib and the active metabolites correlated significantly with the maximum grade of regorafenib-related symptomatic adverse events in the first cycle (11,138 vs. 19,096 pM; P = .035). CONCLUSION: Regorafenib with a low starting dose of 120 mg/day did not achieve the expected DCR. A relationship of unbound exposure with toxicity was found.


Subject(s)
Adenocarcinoma/drug therapy , Colorectal Neoplasms/drug therapy , Phenylurea Compounds/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Pyridines/administration & dosage , Adenocarcinoma/blood , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Japan , Male , Middle Aged , Phenylurea Compounds/pharmacokinetics , Phenylurea Compounds/toxicity , Prospective Studies , Protein Kinase Inhibitors/pharmacokinetics , Protein Kinase Inhibitors/toxicity , Pyridines/pharmacokinetics , Pyridines/toxicity
8.
World J Gastroenterol ; 25(35): 5334-5343, 2019 Sep 21.
Article in English | MEDLINE | ID: mdl-31558877

ABSTRACT

BACKGROUND: Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients' survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM: To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS: We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders; we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS: Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR) = 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and N-classification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION: The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.


Subject(s)
Antineoplastic Agents/therapeutic use , Image Interpretation, Computer-Assisted/methods , Neoadjuvant Therapy , Stomach Neoplasms/therapy , Stomach/diagnostic imaging , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Gastrectomy , Humans , Male , Microscopy/methods , Middle Aged , Neoplasm Staging , Neoplasm, Residual , Prognosis , Proportional Hazards Models , Retrospective Studies , Stomach/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Treatment Outcome , Young Adult
9.
Jpn J Clin Oncol ; 49(10): 910-918, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31219161

ABSTRACT

BACKGROUND: The nutritional status of patients with esophageal squamous cell carcinoma (ESCC) harboring dysphagia is often poor. The efficacy and safety of enteral nutrition (EN) versus total parenteral nutrition (TPN) have not been addressed in patients with ESCC requiring nutritional support during definitive chemoradiotherapy (dCRT). METHODS: We performed a retrospective analysis of 51 locally advanced unresectable ESCC patients with dysphagia receiving EN (n = 28) or TPN (n = 23) during dCRT between 2009 and 2016. RESULTS: Patient characteristics in EN vs. TPN were as follows: median age (range), 67 (34 to 82) vs. 66 (57 to 83); ECOG performance status 0/1/2, 11/15/2 vs. 7/14/2; dysphagia score 2/3/4, 11/15/2 vs. 14/8/1; and primary tumor location Ce/Ut/Mt/Lt/Ae, 4/6/14/3/1 vs. 2/2/16/1/2. Median changes in serum albumin level one month after dCRT were +8.8% (-36 to 40) in EN and -12% (-64 to 29) in TPN (P = 0.00377). Weight, body mass index, and skeletal muscle area were not significantly different between the groups. Median durations of hospitalization were 50 days (18 to 72) in EN and 63 days (36 to 164) in TPN (P = 0.00302). Adverse events during dCRT in EN vs. TPN were as follows: catheter-related infection, 0 vs. 6 (27%); aspiration pneumonia, 3 (11%) vs. 2 (9%); mediastinitis, 3 (11%) vs. 1 (5%); grade ≥3 neutropenia, 6 (21%) vs. 14 (64%) (P = 0.00287); and febrile neutropenia, 0 vs. 6 (27%) (P = 0.00561). CONCLUSIONS: EN may be advantageous for improving serum albumin level, and reducing hematological toxicity and duration of hospitalization compared with TPN during dCRT in ESCC patients.


Subject(s)
Chemoradiotherapy , Deglutition Disorders/complications , Enteral Nutrition , Esophageal Neoplasms/complications , Esophageal Neoplasms/therapy , Parenteral Nutrition, Total , Adult , Aged , Aged, 80 and over , Body Mass Index , Body Weight , Esophageal Neoplasms/blood , Esophageal Neoplasms/pathology , Female , Hospitalization , Humans , Male , Middle Aged , Muscle, Skeletal/pathology , Neoplasm Staging , Nutritional Status , Retrospective Studies , Serum Albumin/metabolism , Treatment Outcome
10.
Int J Clin Oncol ; 23(6): 1189-1195, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29948238

ABSTRACT

BACKGROUND: The efficacy of primary prophylactic granulocyte colony-stimulating factor (G-CSF) in preventing febrile neutropenia (FN) in patients treated with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy remains controversial. We compared the incidence of FN in patients treated with and without primary prophylactic G-CSF. METHODS: We performed a retrospective analysis of 142 patients with locally advanced head and neck or esophageal cancer treated with TPF between January 2009 and March 2017. Among them, 116 patients started TPF without primary prophylactic G-CSF (control group) while 26 patients were given primary prophylactic G-CSF from day 7 of the first cycle of TPF (prophylactic group). RESULTS: The incidence of grade 4 neutropenia during the first cycle of TPF was significantly higher in the control group than in the prophylactic group [58.6% (n = 68) vs. 30.8% (n = 8), p = 0.02]. However, the incidence of FN in the first cycle was not significantly different between the two groups [32 patients (27.5%) in the control group and 8 patients (30.8%) in the prophylactic group (p = 0.62)]. In addition, the mean relative dose intensity throughout all cycles of TPF, as well as the survival time and response after TPF, were also not significantly different between the two groups. CONCLUSIONS: Primary prophylactic G-CSF from day 7 of the first cycle of TPF did not reduce the incidence of FN. Our findings suggest that the timing of primary prophylactic G-CSF, as recommended by the American Society of Clinical Oncology guidelines, should be modified to reduce the incidence of FN in TPF.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Febrile Neutropenia/prevention & control , Granulocyte Colony-Stimulating Factor/therapeutic use , Neoplasms/drug therapy , Practice Guidelines as Topic/standards , Adult , Aged , Cisplatin/administration & dosage , Docetaxel/administration & dosage , Febrile Neutropenia/chemically induced , Febrile Neutropenia/epidemiology , Female , Fluorouracil/administration & dosage , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Neoplasms/pathology , Prognosis , Retrospective Studies , Survival Rate , Young Adult
11.
Int J Clin Oncol ; 23(6): 1084-1089, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29931597

ABSTRACT

PURPOSE: Although oxaliplatin 130 mg/m2 every 3 weeks was approved for advanced gastric cancer in Japan, data regarding S-1 plus oxaliplatin 130 mg/m2 (SOX130) are limited in Japanese patients with advanced gastric cancer. We investigated the feasibility and safety of SOX130 in Japanese patients with advanced gastric cancer. METHODS: Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0-1 were treated with SOX130. The primary endpoint was the 3-cycle completion rate, defined as the proportion of patients who completed the first three cycles with ≥ 80% relative dose intensity of oxaliplatin. RESULTS: Twenty-five patients were enrolled from April 2015 to 2016. The 3-cycle completion rate was 72.0% (90% confidence interval: 53.8-86.1), which was higher than the predetermined threshold rate of 50%. With the median number of cycles being 6 (range, 1-19+), grade 3 or 4 adverse events occurred in 10 patients (40%). Major grade 3 adverse events were anorexia (24%), thrombocytopenia (16%), and neutropenia (12%). No febrile neutropenia or treatment-related deaths occurred. Among 12 patients with measurable lesions, the overall response rate was 58.3%. Median progression-free and overall survival were 5.7 months (95% confidence interval 2.9-8.5) and 13.1 months (95% confidence interval 7.4-19.0), respectively. CONCLUSION: Results indicated that SOX130 was feasible in Japanese patients with advanced gastric cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Asian People , Drug Combinations , Female , Humans , Male , Middle Aged , Neutropenia/chemically induced , Oxaliplatin/administration & dosage , Oxonic Acid/administration & dosage , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Analysis , Tegafur/administration & dosage , Thrombocytopenia/chemically induced , Treatment Outcome
12.
Int J Clin Oncol ; 23(4): 790-798, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29511940

ABSTRACT

BACKGROUND: Recombinant human soluble thrombomodulin (rTM) has been established and introduced in the clinic as a standard treatment for disseminated intravascular coagulation (DIC). However, the efficacy and safety of rTM for DIC associated with solid tumors (DIC-STs) have not been fully established. Here, we performed a retrospective analysis of the clinical outcomes of rTM for DIC-STs and considered a treatment strategy with rTM for DIC-STs. METHODS: Patients with DIC-STs between November 2009 and March 2016 in 2 cancer core hospitals were retrospectively analyzed. Data, including patient background, treatment course, and clinical outcomes of rTM for DIC-STs, were extracted. The clinical outcomes were evaluated by comparing the DIC score, resolution rate, and overall survival (OS) duration. RESULTS: The study included 123 patients with DIC-STs. The median OS in all patients was 41 days. The DIC resolution rate was 35.2%. DIC scores and DIC-related blood test data (fibrin degradation product and prothrombin time-international normalized ratio) significantly improved at the end of rTM administration (P < 0.001). The OS duration was longer in patients who were treated with chemotherapy after DIC onset than in those who were not treated with chemotherapy (median, 178 days vs. 17 days, P < 0.001). In both univariate and multivariate analyses, chemotherapy after DIC onset showed the strongest association with OS. CONCLUSIONS: rTM can at least temporarily improve or maintain the state of DIC-STs. It is suggested that prolongation of survival can be expected when control of DIC and treatment of the underlying disease are compatible.


Subject(s)
Disseminated Intravascular Coagulation/drug therapy , Neoplasms/drug therapy , Recombinant Proteins/therapeutic use , Thrombomodulin/administration & dosage , Adult , Aged , Aged, 80 and over , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/pathology , Female , Humans , Male , Middle Aged , Neoplasms/complications , Neoplasms/pathology , Retrospective Studies , Survival Rate , Syndrome , Treatment Outcome
13.
Gastric Cancer ; 21(2): 338-344, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28577228

ABSTRACT

BACKGROUND: Several studies have demonstrated the benefit of hepatectomy for treating gastric cancer (GC) with liver-limited metastases (LLM). The survival benefit of hepatectomy compared with that of systemic chemotherapy is unknown, particularly in patients with multiple LLM. This study investigated the survival benefit of hepatectomy compared with that of systemic chemotherapy administered to patients with GC with multiple LLM. METHODS: We retrospectively reviewed the data of consecutive patients with GC with two or three LLM who underwent hepatectomy or received systemic chemotherapy as initial treatment at the Shizuoka Cancer Center between December 2004 and December 2015. RESULTS: Nine of 24 patients who met the inclusion criteria underwent hepatectomy, and 15 received chemotherapy. In the hepatectomy group, all patients achieved R0 resection and none died during hospitalization. Three patients received adjuvant chemotherapy. Disease recurred in eight patients (88.9%). In the chemotherapy group, three patients underwent hepatectomy following initial chemotherapy and did not experience recurrence or death during follow-up. Median follow-up was 47.9 months and median overall survival (OS) was 38.1 and 24.8 months in the chemotherapy and hepatectomy groups, respectively. Multivariate analysis of OS, including initial treatment, revealed that unilobar liver metastasis was the only independent favorable prognostic factor. CONCLUSIONS: Although hepatectomy for patients with GC with multiple LLM is not recommended as the initial therapy, it prolonged the survival of patients with tumors controlled using systemic chemotherapy.


Subject(s)
Adenocarcinoma/secondary , Adenocarcinoma/surgery , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Stomach Neoplasms/pathology , Adenocarcinoma/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Hepatectomy/mortality , Humans , Kaplan-Meier Estimate , Liver Neoplasms/drug therapy , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery
14.
Gan To Kagaku Ryoho ; 44(11): 1021-1023, 2017 Nov.
Article in Japanese | MEDLINE | ID: mdl-29138380

ABSTRACT

According to the REGARD and RAINBOW trials, ramucirumab(RAM)was introduced as second-line therapy for advanced or metastatic gastric cancer. RAM may impair wound healing due to the inhibition of angiogenesis; details on the postoperative course of patients who underwent surgery during RAM treatment remain unclear. Between 2011 and 2016, 93 patients with incurable gastric cancer were treated with RAM in our institute. Among them, 3 patients underwent surgery after RAM treatment. Case 1: A 74-year-old man with liver metastasis from gastric cancer was treated with a paclitaxel(PTX)plus RAM regimen. Perforation of the stomach was observed 3 days after final RAM administration. He was successfully treated with omental repair and discharged 19 days after surgery. Case 2: A 31-year-old woman with peritoneal recurrence after total gastrectomy received the PTX plus RAM regimen as second-line treatment. Stenting was performed for rectal stenosis. Perforation of the rectum just proximal of the stent was observed 5 days after final RAM administration. Ileostomy was performed. Closure of the perforation was not obtained until the patient died 210 days after surgery. Case 3: A 60-year-old man with remnant gastric cancer received the PTX plus RAM regimen. Accidentally, the enteral feeding tube was removed. Six weeks after the cessation of RAM administration, the enteral feeding tube was inserted under general anesthesia. He was discharged 4 days after surgery. If surgery is required in patients receiving RAM treatment, sufficient drug withdrawal is desirable. If emergency surgery is needed, less invasive procedures should be selected to the maximum extent possible.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized , Combined Modality Therapy , Female , Gastrectomy , Humans , Male , Middle Aged , Neoplasm Metastasis , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Treatment Outcome , Ramucirumab
15.
Pancreatology ; 17(6): 983-989, 2017.
Article in English | MEDLINE | ID: mdl-29066391

ABSTRACT

BACKGROUND/OBJECTIVE: Whether gastrojejunostomy (GJJ) or duodenal stent (DS) placement is preferable for treatment of gastric outlet obstruction (GOO) in patients with unresectable pancreatic cancer is unclear. We compared the usefulness of GJJ with that of DS placement in these patients. METHODS: We retrospectively reviewed 66 consecutive patients with unresectable pancreatic cancer who underwent GJJ or DS placement for symptomatic GOO. RESULTS: We analyzed 30 patients who underwent GJJ and 23 who underwent DS placement. Peritoneal metastasis was more common in the DS group. Median survival after the first intervention was similar in both groups. Although clinical success (maintaining a GOO Scoring System score ≥2 for more than 7 days) rate was significantly higher in the GJJ group (100% vs. 81%), clinical benefit (maintaining a score ≥2 for more than half of their survival after the first intervention) rate was similar between the GJJ and DS groups (66.7% vs. 69.7%), even among patients who survived for ≥90 days (73.3% vs. 75.0%). Further, the proportion of patients who could receive planned chemotherapy after the first intervention was higher and the time to administration of chemotherapy was significantly shorter in the DS group (9 vs. 32 days). Major complication rate was similar in both groups. CONCLUSIONS: These findings suggest that DS placement is as effective as GJJ for the treatment of GOO in patients with unresectable pancreatic cancer, even in those with a long life expectancy. DS placement might be more beneficial than GJJ in patients for whom chemotherapy is planned.


Subject(s)
Duodenum/surgery , Gastric Bypass , Gastric Outlet Obstruction/surgery , Pancreatic Neoplasms/surgery , Stents , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Female , Humans , Male , Middle Aged , Palliative Care , Retrospective Studies , Treatment Outcome , Pancreatic Neoplasms
16.
Cancer Chemother Pharmacol ; 80(3): 575-582, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28730292

ABSTRACT

PURPOSE: Taxane monotherapy is widely used for advanced gastric cancer (AGC) after failure of standard first-line chemotherapy with fluoropyrimidine and cisplatin. Triplet chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is a promising regimen for first-line chemotherapy of AGC. The aim of this study was to evaluate the efficacy of taxane monotherapy in patients refractory to DCS. METHODS: We retrospectively evaluated the efficacy and safety of taxane monotherapy in patients with AGC refractory to first-line therapy with DCS between January 2010 and April 2015. Selection criteria were as follows: ECOG PS of 0-2, treatment with taxane monotherapy in second-line or third-line therapy after failure of second-line irinotecan, absence of massive ascites, and adequate organ function. RESULTS: A total of 30 patients were included in this study. Of these, 15 patients received paclitaxel while another 15 received nanoparticle albumin-bound paclitaxel in either second- or third-line treatment. Median age for the second/third-line group was 64.0/62.0 (range 27-75/42-75); 14/13 (93.3/86.7%) had ECOG PS of 0 or 1. No patients achieved complete or partial response and stable disease was observed in 37.5/35.7% of the patients in the second/third line. Median progression-free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line group, respectively. The incidences of any grade ≥3 adverse events in the second-line group and the third-line group were 60.0 and 33.3%, respectively. There was no treatment-related death. CONCLUSIONS: Taxane monotherapy after DCS failure had acceptable toxicities but was ineffective in AGC patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bridged-Ring Compounds/therapeutic use , Cisplatin/therapeutic use , Oxonic Acid/therapeutic use , Stomach Neoplasms/drug therapy , Taxoids/therapeutic use , Tegafur/therapeutic use , Adult , Aged , Docetaxel , Drug Combinations , Female , Humans , Male , Middle Aged , Retrospective Studies , Stomach Neoplasms/pathology
17.
BMC Cancer ; 17(1): 59, 2017 01 17.
Article in English | MEDLINE | ID: mdl-28095814

ABSTRACT

BACKGROUND: Chemoradiotherapy (CRT) and bio-radiotherapy (BRT) are recognized as standard therapies for head and neck cancer (HNC). Aspiration pneumonia after CRT or BRT is a common late adverse event. Our aim in this study was to evaluate the cause-specific incidence of aspiration pneumonia after CRT or BRT and to identify its clinical risk factors. METHODS: We performed a retrospective analysis of 305 patients with locally advanced HNC treated by CRT or BRT between August 2006 and April 2015. RESULTS: Of these 305 patients, 65 (21.3%) developed aspiration pneumonia after treatment. The median onset was 161 days after treatment. The two-year cause-specific cumulative incidence by CRT or BRT was 21.0%. Multivariate analysis revealed five independent risk factors for aspiration pneumonia, namely, habitual alcoholic consumption, use of sleeping pills at the end of treatment, poor oral hygiene, hypoalbuminemia before treatment, and the coexistence of other malignancies. A predictive model using these risk factors and treatment efficacy was constructed, dividing patients into low- (0-2 predictive factors), moderate- (3-4 factors), and high-risk groups (5-6 factors), the two-year cumulative incidences of aspiration pneumonia of which were 3.0, 41.6, and 77.3%, respectively. Aspiration pneumonia tended to be associated with increased risk of death, although this was not statistically significant (multivariate-adjusted hazard ratio 1.39, P = 0.18). CONCLUSION: The cause-specific incidence and clinical risk factors for aspiration pneumonia after definitive CRT or BRT were investigated in patients with locally advanced HNC. Our predictive model may be useful for identifying patients at high risk for aspiration pneumonia.


Subject(s)
Cetuximab/adverse effects , Chemoradiotherapy/adverse effects , Head and Neck Neoplasms/therapy , Pneumonia, Aspiration/epidemiology , Case-Control Studies , Female , Humans , Incidence , Male , Pneumonia, Aspiration/etiology , Retrospective Studies
18.
Cancer Chemother Pharmacol ; 78(4): 809-14, 2016 10.
Article in English | MEDLINE | ID: mdl-27566700

ABSTRACT

PURPOSE: Although irinotecan monotherapy is often used in third-line treatment after the failure of taxanes in Japanese clinical practice, its survival benefit is still unclear. The aim of this study is to investigate the efficacy and safety of irinotecan monotherapy as third-line treatment. METHODS: Clinical data from consecutive patients in whom irinotecan had been initiated as third-line treatment between December 2003 and July 2015 in Shizuoka Cancer Center were retrospectively analyzed. Patients who were refractory or intolerant to fluoropyrimidine with or without platinum in first-line treatment and subsequent therapy with taxanes were included in this study. Irinotecan was administered at 150 mg/m(2) every 2 weeks. RESULTS: The data of 50 patients who met the inclusion criteria were analyzed. The overall response rate was 18.4 % (7/38) among the patients with measurable disease. The median progression-free survival time was 66 days, and the median survival time was 180 days from the initiation of irinotecan therapy. The major grade 3 or 4 adverse events including neutropenia, fatigue, and anorexia were observed in 12 (24 %), 8 (16 %), and 7 (14 %), respectively. No treatment-related deaths occurred. Thirteen patients (26 %) required a dose reduction to 120 mg/m(2) or less from the initiation of irinotecan. CONCLUSIONS: This study suggests that irinotecan as third-line treatment has an anti-tumor effect and is feasible with optimal dose modification for advanced gastric cancer.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/analogs & derivatives , Stomach Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/therapeutic use , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Irinotecan , Kaplan-Meier Estimate , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome
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