The impact of single-hetero UGT1A1 on clinical outcomes of irinotecan monotherapy in gastric cancer after fluoropyrimidine, platinum, and taxanes: Multicenter retrospective study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 296-296
Author(s):  
Ken Ito ◽  
Yoshito Komatsu ◽  
Satoshi Yuki ◽  
Shintaro Nakano ◽  
Hiroshi Nakatsumi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retrospective Study ◽  
Treatment Guidelines ◽  
Performance Status ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Her2 Status ◽  
Gastric Cancer Treatment ◽  
Third Line ◽  
The Impact

296 Background: Japanese gastric cancer treatment guidelines (5th edition) recommend irinotecan (IRI) after fluoropyrimidine, platinum and taxanes as a third line chemotherapy. We previously reported that patients with UGT1A1 single heterozygous (SH) had significantly high frequency of severe hematological adverse events (AEs) compared to patients with UGT1A1 wild type (WT) in IRI monotherapy for advanced gastric cancer (AGC). However, it remains unclear that UGT1A1 SH affect efficacy and safety of IRI after fluoropyrimidine, platinum and taxanes compared to WT as a salvage line. Methods: We retrospectively analyzed the clinical data of patients who received IRI monotherapy after fluoropyrimidine, platinum and taxanes in the multi-institutional retrospective study. From January 2010 to December 2017, 69 eligible patients were registered from 8 centers in Japan. Results: Forty one patients with UGT1A1 WT and 28 patients with UGT1A1 SH were included in this study. In WT/SH patients, performance status 0/1/≥2 was 12/25/4 and 5/17/6, treatment line 3rd/4th or later was 33/8 and 26/2, HER2 status positive/negative was 12/29 and 5/23, respectively. In WT/SH patients, rate of initial dose reduction was 22 and 28% (P = 0.363), median relative dose intensity (RDI) was 82% and 80% (P = 0.309). Of 88 patients who have measurable lesions, the overall response rate (ORR) was 5.7% and 4.2% (P = 1.000), disease control rate (DCR) was 54% and 38% (P = 0.289). Median progression free survival was 3.2 and 2.1 months (HR 0.607, P = 0.058) and median overall survival from initial day of IRI monotherapy was 10.0 and 7.0 months (HR 0.618 P = 0.086). In WT/SH patients, severe hematological AEs (≥G3) were observed more frequently in patients with UGT1A1 SH (WT: 43% and SH: 68%, P = 0.050), although frequency of severe non-hematological AEs (≥G3) were not significantly different in both groups (13% and 25%, P = 0.211). Conclusions: Compared to UGT1A1 WT, UGT1A1 SH status may be associated with poor efficacy and be a risk factor of higher frequency of severe hematological AEs.

Treatment outcome and safety of docetaxel as the third-line chemotherapy in advanced gastric cancer after progression or after failure of FOLFOX and FOLFIRI-based sequential chemotherapy.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 133-133
Author(s):  
I. Hwang ◽  
J. Kang ◽  
B. Park ◽  
S. Park ◽  
M. Jang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Progression ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
The Third ◽  
Third Line ◽  
Grade 3 ◽  
Line Chemotherapy

133 Background: We performed multicenter retrospective study to evaluate the activity and the safety of a docetaxel as the third-line chemotherapy in advanced gastric cancer (AGC) patients who had undergone oxaliplatin (FOLFOX) and irinotecan (FOLFIRI)-based chemotherapy regimens. Methods: Thirty-eight patients with AGC previously treated were eligible for this study. Patients received docetaxel 30 mg/m2 +/- cisplatin 30 mg/m2 IV on day 1, 8 or docetaxel 60 mg/m2 +/- cisplatin 60 mg/m2 IV on day 1 every 3 weeks until disease progression, and responses were assessed after every two cycles according to RECIST criteria and toxicity was evaluated by NCI-CTC. Results: Thirty-two out of 38 patients were evaluable for response. A total of 95.1 cycles of chemotherapy (median 2, range 0.5–7) were administered. Relative dose intensities of docetaxel and cisplatin were 93.4% and 87.8%, respectively. The overall response rate was 15.6% and the disease control rate was 50%. With a median follow-up duration of 3.1 months (range 0.3-14.3 months), 36 patients had disease progression, and 34 patients had died at the time of analysis. The median progression-free survival was 1.8 months (95% CI, 1.3–2.3 months). The median overall survival was 3.1 months (95% CI, 2.3–3.9 months). Grade 3 or 4 hematologic toxicities included neutropenia in thirteen patients (38.3%), febrile neutropenia in four patients (11.7%). and thrombocytopenia in one patient (2.9%). Other grade 3 or 4 toxicities included neuropathy in three patients (8.8%) and mucositis in two patients (5.9%). There were three treatment-related deaths (8.8%) caused by infection associated with neutropenia. Conclusions: Salvage docetaxel chemotherapy in AGC patients failed in oxaliplatin and irinotecan-based treatment is not recommend routinely. However, selected patients with good performance status and sufficient albumin levels may have derived some survival benefits from salvage chemotherapy. No significant financial relationships to disclose.

scholarly journals The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wen-Long Guan ◽  
Yue Ma ◽  
Yue-Hong Cui ◽  
Tian-Shu Liu ◽  
Yan-Qiao Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mismatch Repair ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Clinicopathological Characteristics ◽  
Her2 Status ◽  
Clinical Role ◽  
Record System ◽  
Free Survival ◽  
The Impact

BackgroundThe clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival.MethodsPatients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system.ResultsA total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively).ConclusionsdMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

Efficacy and safety of irinotecan monotherapy as third line treatment for advanced gastric cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 113-113
Author(s):  
Takeshi Kawakami ◽  
Nozomu Machida ◽  
Masahiro Kawahira ◽  
Sadayuki Kawai ◽  
Yosuke Kito ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Peritoneal Dissemination ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Third Line ◽  
Gastric Cancer Patients ◽  
Metastatic Sites ◽  
Line Chemotherapy

113 Background: Several randomized trials demonstrated the survival benefit in advanced gastric cancer patients (AGC pts) receiving irinotecan or taxanes as second-line chemotherapy (SLC). Taxanes are used for SLC in daily clinical practice in Japan because of its less toxicity, especially in AGC pts with peritoneal dissemination, compared with irinotecan. Although irinotecan is often administered after refractory or intolerant to taxanes as SLC, the efficacy and safety of irinotecan as third-line chemotherapy (TLC) is still unclear. Methods: We retrospectively investigated the data of AGC pts administered irinotecan 150mg/m2 as TLC every two weeks until disease progression, unacceptable toxicity, or pts’ refusal between December 2002 and June 2015. Inclusion criteria were (1) age 75 years or less (2) refractory or intolerant to fluoropyrimidine with or without platinum as first-line chemotherapy (3) refractory or intolerant to taxanes as SLC. Results: A total of 52 pts were analyzed. Pts’ characteristics were as follows: median age, 66 (range, 33-75) years; male/female, 35/17 pts; ECOG PS 0-1/2, 42/10 pts; peritoneal dissemination +/-, 32/20 pts; ascites +/-, 22/30 pts, number of metastatic sites 1-2/3-4, 44/8 pts. Median follow-up period was 548 (141-1931) days. Median progression-free survival was 70 days (95%CI 49-137) and median overall survival was 144 days (95%CI 120-231) from the initiation of irinotecan administration. Response rate and disease control rate was 10.8% and 50.4%, respectively. Relative dose intensity was 74.7% (56 mg/m2/week); 14 pts needed dose reduction in the first course, and 22 pts after the second course. Grade 3 or 4 neutropenia, anemia, diarrhea, nausea, and febrile neutropenia were observed in 13 (25%), 21 (40.4%), 5 (9.6%), 3 (5.8%) and 3 (5.8%) pts, respectively. No treatment-related death was observed. Conclusions: This study suggests that irinotecan monotherapy as TLC has acceptable anti-tumor effect and has manageable toxicity in appropriately selected AGC pts.

Phase II trial of S-1 plus split cisplatin (SSP) in patients with advanced gastric cancer (HGCSG0702): Final report.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 113-113
Author(s):  
Satoshi Yuki ◽  
Yoshito Komatsu ◽  
Hiraku Fukushima ◽  
Takahide Sasaki ◽  
Yoshimitsu Kobayashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Final Report ◽  
Free Survival

113 Background: On the basis of SPIRITS trial, S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with advanced gastric cancer (AGC) in Japan (Koizumi W, et al. Lancet Oncol, 2008). However, conventional S-1 plus cisplatin (60mg/m2) regimen requires hospitalization for hydration. Therefore, we conducted phase II trial of S-1 plus split Cisplatin (SSP) for outpatient chemotherapy. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 75, ECOG performance status (PS) of 0 to 1; adequate organ function; and written informed consent. S-1 (40 mg/m2) was given orally, twice daily for 21 days, and cisplatin (30 mg/m2) was given intravenously on day 1 and 15, followed by 2-week rest period, within a 5-week cycle. Primary endpoint was the response rate (RR), and secondary endpoints were progression-free survival, overall survival, safety profile, and non-hospitalized survival. Results: Between Mar 2008 and Mar 2012, 40 pts were enrolled. Patients characteristics were as follows: median age 63 years (range 41-75), Male: female 30:10, PS 0:1 33:7, diffuse: intestinal 23:17. Median number of cycles was 3. The main grade 3-4 AE were neutropenia (37.5%), anemia (30%), anorexia (30%) and fatigue (15%). These toxicities were safely managed. The median relative dose intensity of S-1 was 0.782, and cisplatin was 0.824. Response rate was 57.5% (95%CI 42.2-72.8%) and disease control rate was 90.0%. Median progression-free survival was 6.1 months (95%C.I. 3.0-9.1 months) and median survival time was 15.8 months (95%C.I. 12.7-18.8 months). Conclusions: SSP showed comparable tolerability and efficacy to SPIRITS trial. In addition, most patients underwent the treatment without hospitalization. SSP may be one of practical alternatives for AGC.

Association of statins and nivolumab activity in patients with metastatic renal cell carcinoma (mRCC): Results from the phase II nivoren—GETUG AFU 26 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 359-359
Author(s):  
Emeline Colomba ◽  
Ronan Flippot ◽  
Cécile Dalban ◽  
Sylvie Negrier ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Modulation ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Population Based ◽  
Metabolic Reprogramming ◽  
Oncogenic Signaling ◽  
Grade 3 ◽  
The Impact

359 Background: Statins are HMG-CoA inhibitors that regulate several mechanisms involved in tumor growth, including mitochondrial metabolism, activation of oncogenic signaling pathways, and immune modulation. Population-based studies showed that statin intake may be negatively associated with RCC onset. The impact of statins on response to immunotherapy in mRCC is unknown. Herein we study the association between statin administration and outcomes in patients with mRCC treated with nivolumab in the NIVOREN-GETUG AFU 26 phase II trial (NCT03013335). Methods: Patients with mRCC who failed previous VEGFR inhibitors were included. We assessed nivolumab activity, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to statin intake at baseline. Toxicity was assessed using CTCAE v4.0. Results: Overall,133 patients were treated with statins at baseline among 702 evaluable for concomitant therapies (19%). Among them, median age was 68 (49-90), 84% were male, 85% had a performance status ≥ 80%, 42% were overweight and 20% obese. Patients treated with statins had mostly good (23%) or intermediate (58%) IMDC risk, 64% had grade 3 or 4 tumors, and nivolumab was given in a third line setting or more in 55%. Median follow-up was 23.9 months (95%CI 23.0-24.5) in the overall cohort. The ORR was 26% in patients treated with statins, PFS 5.0 months (CI95% 3.0 – 5.5), OS 27.9 months (CI95% 19.4-30.3). Outcomes of patients with or without statins did not differ significantly. Similar rates of grade 3-5 TRAE were reported in patients with (20%) or without (18%) statin intake. Conclusions: This is the first study to evaluate statin intake and outcomes with nivolumab in patients with mRCC. Despite numerically higher ORR, statins were not significantly associated with improved outcomes. These data require other analyzes considering other factors such as BMI and other comorbidities. Further studies may help better understand the interplay between immunity and metabolic reprogramming in RCC.

Transition of molecular target agent therapy in advanced hepatocellular carcinoma: A multicenter, retrospective study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 317-317
Author(s):  
Kazufumi Kobayashi ◽  
Sadahisa Ogasawara ◽  
Aya Takahashi ◽  
Yuya Seko ◽  
Satoshi Tsuchiya ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Staging System ◽  
Sequential Therapy ◽  
Molecular Target ◽  
Advanced Hepatocellular Carcinoma ◽  
Entire Cohort ◽  
Significant Difference

317 Background: There have been considerable advances in systemic chemotherapy for hepatocellular carcinoma (HCC) in recent times. Currently, four molecular target agents (MTA) are available for HCC treatment in Japan. Sequential therapy using multiple MTAs is being considered as the gold standard of treatment. However, the effectiveness of the treatment strategy transition for HCC remains unclear. The present study aimed to clarify the current practical use of MTAs and its effectiveness in HCC treatment. Methods: In this multicenter, retrospective study, we collected and analyzed the clinical data of 877 patients who underwent MTA therapy for HCC from June 2009 to March 2019 at several institutes in Japan. The patients were classified into 3 groups as per the period of initial MTA treatment beginning (period 1: 2009–2012, n = 267; period 2: 2013–2016, n = 352; period 3: 2017–2019, n = 258). These 3 periods were defined to have approximately same term. Period 3 means the era of multiple MTAs because of the approval of regorafenib in Japan in 2017. We assessed the patient characteristics, MTA use, and prognosis of the 3 groups. Results: The proportion of patients with advanced-stage HCC, defined according to the Barcelona Clinic Liver Cancer staging system, in each period was 70.1%, 66.5%, and 62.0% in period 1, 2, and 3, respectively. MTA use for intermediate stages increased with the passage of time ( p = 0.052). The proportion of multiple MTAs use was remarkably increased in the 3 groups (1.1%, 10.2%, and 42.6%, respectively, p < 0.0001). Child-Pugh score, proportion of macrovascular invasion, extrahepatic metastasis, and α-fetoprotein (AFP) ≥400 ng/mL showed no significant difference among the 3 groups. The median overall survival was 11.9 months for the entire cohort and 10.4, 11.3, and 15.2 months, for period 1, 2, and 3, respectively. It is noteworthy that the prognosis of patients with HCC improved over time ( p = 0.016). With respect to progression-free survival, the median value was 3.0 months for the entire cohort and 2.7, 2.8, and 4.7 months for period 1, 2, and 3, respectively ( p < 0.0001). The treatment duration was also prolonged with time (2.7, 3.2, and 6.6 months for period 1, 2, and 3, respectively; p < 0.0001). Multivariate analysis using Cox proportional hazard model showed that HCV infection, Child-Pugh score, performance status, α-fetoprotein ≥400 ng/mL, presence of macrovascular invasion, and period 3 for initial MTA introduction were independent prognostic factors. Conclusions: Sequential therapy with multiple MTAs has gained popularity with time and is considered to improve patient prognosis. The development of MTA therapy for HCC is expected to continue. Therefore, further studies are needed to help determine the appropriate drugs, the sequence of MTA use, and the precise transition time.

Efficacy of weekly paclitaxel-bevacizumab combination in advanced nonsquamous non-small cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21086-e21086
Author(s):  
Geoffroy Bilger ◽  
Anne-Claire Toffart ◽  
Marie Darasson ◽  
Michaël Duruisseaux ◽  
Lucie Ulmer ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Multicentric Study ◽  
Significant Difference ◽  
Third Line ◽  
And Performance ◽  
Line Setting

e21086 Background: With the growing role of immunotherapy (ICI) as first-line setting for advanced NSCLC, strategies must be redefined after failure. The combination paclitaxel-bevacizumab showed in the ULTIMATE trial a significant superiority versus docetaxel as second or third-line treatment. Limited restropective studies has demonstrated unexpected efficacy of chemotherapy after prior progression on ICI. This combination could be use as salvage treatment following ICI. Methods: This multi-centric retrospective study identifies patients treated with the combination paclitaxel-bevacizumab in metastatic non-squamous NSCLC as second-line therapy or beyond. Main objectives were to describe safety and efficacy of this combination, with a special attention to the sub-group treated just after ICI. Results: From January 2010 to February 2020, 314 patients started the paclitaxel-bevacizumab combination : 55% male, with a median age of 60 years, 27% with a performance status ≥2, 45% with brain metastases. A majority of patients were treated in second (20%) and third-line (39%), and 28% were treated just after ICI failure (88/314). Objective response rate (ORR) was 40% and disease control rate was 77 %. Median progression-free survival (PFS) and overall survival (OS) were 5,7 months [IQ,3,2–9,6] and 10,8 months [IQ,5,3–19,6] respectively. All grades adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued a monotherapy alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compare to those not previously treated with ICI (ICI-) : 7,0 months [IQ,4,2–11,0] vs 5,2 months [IQ,2,9–8,8] p (log-rank) = 0,01. There was not statistically significant difference in term of OS between this two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment (ICI+) and performance status. Conclusions: This study confirms an acceptable toxicity profile associated with interesting efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non–squamous NSCLC patients, particularly after progression with ICI.

scholarly journals Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Florence Chamberlain ◽  
Sheima Farag ◽  
Constance Williams-Sharkey ◽  
Cecilia Collingwood ◽  
Lucia Chen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Individual Risk ◽  
Duration Of Treatment ◽  
Ecog Performance Status ◽  
Third Line ◽  
Grade 3 ◽  
Dose Reductions

Abstract Background Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. Methods Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. Results Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8–14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2–28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3–4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. Conclusion Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.

scholarly journals Evaluation of the Japanese Gastric Cancer Association?s Gastric Cancer Treatment Guidelines for Popular Use

2004 ◽  
Vol 7 (1) ◽  
pp. 41-45
Author(s):  
Takashi Ichikura ◽  
Toshiya Ogawa ◽  
Takashi Majima ◽  
Susumu Saigusa ◽  
Yoshihisa Yaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Treatment ◽  
Treatment Guidelines ◽  
Japanese Gastric Cancer Association ◽  
Gastric Cancer Treatment
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