scholarly journals Sorafenib-Regorafenib Sequential Therapy in Japanese Patients with Unresectable Hepatocellular Carcinoma—Relative Dose Intensity and Post-Regorafenib Therapies in Real World Practice

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1517 ◽  
Author(s):  
Wang ◽  
Tsuchiya ◽  
Kurosaki ◽  
Yasui ◽  
Inada ◽  
...  
Keyword(s):  
Real World ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Japanese Patients ◽  
Relative Dose Intensity ◽  
Free Survival ◽  
Median Total Dose ◽  
Clinically Significant

Background: We aimed to explore the relative dose intensity (RDI) and post-regorafenib treatments in regorafenib therapy. Methods: The medical records of 38 patients treated with regorafenib between July 2017 and June 2019 at our institution were collected. The RDI of regorafenib for the first month (1M-RDI) was calculated. Results: The overall survival (OS) and progression-free survival (PFS) were 12.4 and 3.7 months. The objective response rate and disease control rate were 13.2% and 71.1%. The median total dose of regorafenib in the first month was 2080 mg (240–3360 mg), and the median 1M-RDI was 61.9% (7.1%–100%). Patients with 1M-RDI ≥ 50% showed significantly longer OS and PFS than patients with 1M-RDI < 50% (HR 0.19, 95% CI 0.08–0.48, p = 0.0004 and HR 0.2, 95% CI 0.08–0.52, p = 0.0008). A 1M-RDI ≥ 50% (HR 0.18, 95% CI 0.06–0.55, p = 0.002) and hand–foot skin reaction (HR 0.03, 95% CI 0.008–0.16, p < 0.0001) were independently associated with OS. Post-regorafenib therapies were performed in 19 (86.4%) of 22 patients who had stopped regorafenib due to disease progression. Conclusion: A 1M-RDI ≥ 50% is clinically significant. Post-regorafenib therapies are commonly performed in real-world practice.

scholarly journals Effectiveness of nivolumab affected by prior cetuximab use and neck dissection in Japanese patients with recurrent or metastatic head and neck cancer: results from a retrospective observational study in a real-world setting

2021 ◽  
Author(s):  
Shin Kariya ◽  
Yasushi Shimizu ◽  
Nobuhiro Hanai ◽  
Ryuji Yasumatsu ◽  
Tomoya Yokota ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Dissection ◽  
Neck Cancer ◽  
Median Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Free Survival

Abstract Background To examine the effect of prior use of cetuximab and neck dissection on the effectiveness of nivolumab, we conducted a large-scale subgroup analysis in Japanese patients with recurrent/metastatic head and neck cancer. Methods Data on the effectiveness of nivolumab were extracted from patient medical records. All patients were analyzed for effectiveness by prior cetuximab use. In the analyses for prior neck dissection, only patients with locally advanced disease were included. Results Of 256 patients analyzed, 155 had received prior cetuximab. Nineteen of 50 patients with local recurrence underwent neck dissection. The objective response rate was 14.7 vs 17.2% (p = 0.6116), median progression-free survival was 2.0 vs 3.1 months (p = 0.0261), and median overall survival was 8.4 vs 12 months (p = 0.0548) with vs without prior cetuximab use, respectively. The objective response rate was 23.1 vs 25.9% (p = 0.8455), median progression-free survival was 1.8 vs 3.0 months (p = 0.6650), and median overall survival was 9.1 vs 9.9 months (p = 0.5289) with vs without neck dissection, respectively. Conclusions These findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck dissection history. Trial registration number UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

A dose attenuated schedule of irinotecan and capecitabine in combination with celecoxib in advanced colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3584-3584
Author(s):  
B. F. El-Rayes ◽  
A. F. Shields ◽  
U. Vaishampayan ◽  
L. K. Heilbrun ◽  
M. M. Zalupski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Free Survival ◽  
Study Results ◽  
Cox 2

3584 Background: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in the majority of colorectal cancers. Inhibition of the COX-2 enzyme can sensitize colorectal cancer cells to the apoptotic effects of chemotherapeutic agents and block angiogenesis. This phase II study was undertaken to determine the effects of adding celecoxib to a dose attenuated irinotecan and capecitabine regimen. Methods: The primary objective was to estimate the objective response rate of patients with metastatic colorectal cancer treated with irinotecan, capecitabine, and celecoxib. Previously untreated patients, except for adjuvant therapy, with metastatic colorectal adenocarcinoma were eligible for this study. Patients received irinotecan 70 mg/m2 (over 30 minutes) on days 1 and 8, and capecitabine 2,000 mg/m2/day from day 1 to 14 of a 21-day cycle. Celecoxib was administered at a dose of 400 mg twice-daily starting on day -7 until termination from study. Results: A total of 51 patients (median age 58 years) have been enrolled on the study. The results presented are for the first 48 patients registered to the study. Median performance status was 1. A median number of 5.5 cycles (range 0- 18) were administered. In an intention to treat analysis, objective response rate was 50%. The median progression free survival was 6.9 months (90%CI; 4.7–8.2). Median survival is ≥19.4 months. No treatment related deaths were observed. The only grade 4 toxicity was diarrhea in 2 (4%) patients. Grade 3 toxicities were diarrhea (33%), hand-foot syndrome (8%), nausea (13%), vomiting (8%) and neutropenia (12%). Conclusion: Lowering the dose intensity of irinotecan in this study did not appear to compromise the treatment outcome and markedly improved the therapeutic index of this combination. Celecoxib can be safely administered in combination with irinotecan and capecitabine. Based on the observed progression free survival and response rate, the regimen has promising activity. No significant financial relationships to disclose.

Effect of comorbidities/comedications on treatment outcomes with sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC): Subgroup analyses from the STAR-TOR registry.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 631-631
Author(s):  
Stephan Bernhardt ◽  
Marcus Hubbe ◽  
Michael Rink ◽  
Lothar Bergmann ◽  
Martin Boegemann ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
Exact Test ◽  
Sunitinib Treatment ◽  
Kaplan Meier ◽  
Cutoff Date

631 Background: Sunitinib remains an important treatment option for mRCC, but the effect of comorbidities/comedications on sunitinib treatment outcomes have not been fully explored. Methods: Data were collated from STAR-TOR, an ongoing real-world registry. Cutoff date for analysis was 19 June 2019. This subgroup analysis assessed the presence or absence of hypertension (HTN), and the use or non-use of statins and proton pump inhibitors (PPIs), determined at the time of entry to the registry. Treatment endpoints were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). OS and PFS were analyzed by Kaplan-Meier methods. Differences within subgroups were tested using Log-rank test for OS and PFS, and Fisher’s exact test for ORR. Results: 557 sunitinib-treated pts were analyzed; 366 had HTN and 191 did not, 130 used statins and 427 did not, and 165 used PPIs and 392 did not. Median (m) OS (95% confidence intervals) was similar in pts with and without HTN (25.4 [21.1, 31.5] vs 21.5 [15.2, 28.0] months; p = 0.215). mPFS (8.0 [6.5, 9.9] vs 6.3 [5.4, 8.2] months; p = 0.140) and ORR (31.2% vs 30.9%; p = 1.000) were also similar in pts with and without HTN. mOS was similar in pts who used statins vs those who did not (27.8 [20.2, 35.4] vs 24.0 [19.4, 27.3] months; p = 0.884), while mPFS was significantly longer in pts who used statins (9.4 [6.5, 13.6] vs 6.9 [5.7, 8.2] months; p = 0.044). ORR was 37.8% vs 29.0% in pts who did and did not use statins (p = 0.072). mOS was significantly shorter in pts who used PPIs vs those who did not (20.2 [14.9, 28.3] vs 25.7 [22.7, 33.0] months; p = 0.021). mPFS (5.8 [4.6, 8.2] vs 8.0 [6.5, 9.8] months; p = 0.091) and ORR (26.6% vs 33.0%; p = 0.177) were similar in pts who did and did not use PPIs. Conclusions: In sunitinib-treated pts with mRCC in a real-world registry, mPFS was significantly longer and there was a trend toward better ORR in pts who used statins, whereas mOS was significantly shorter and there was a trend toward shorter mPFS in pts who used PPIs. Common comedications may affect sunitinib treatment outcomes in pts with mRCC.

The Role of the Albumin-Bilirubin Score for Predicting the Outcomes in Japanese Patients with Advanced Hepatocellular Carcinoma Treated with Ramucirumab: A Real-World Study

Oncology ◽  
2020 ◽  
pp. 1-12
Author(s):  
Takeshi Hatanaka ◽  
Atsushi Naganuma ◽  
Mitsuhiko Shibasaki ◽  
Tatsuya Kohga ◽  
Yosuke Arai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real World ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Low Incidence ◽  
Number Of Cycles

<b><i>Aim:</i></b> The aim of this retrospective study was to investigate the efficacy and safety of ramucirumab treatment under real-world conditions and to clarify the role of albumin-bilirubin (ALBI) score in predicting outcomes. <b><i>Methods:</i></b> Between June 2019 and May 2020, a total of 16 patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab in Gunma Saiseikai Maebashi Hospital and its affiliated hospitals was included. <b><i>Results:</i></b> The median age was 71 (interquartile range [IQR] 65–74) years old, and 12 patients (75.0%) were male. The modified ALBI (mALBI) grade was 1, 2a, and 2b at baseline in 4 (25.0%), 3 (18.8%), and 9 patients (56.3%), respectively. The Barcelona Clinic Liver Cancer stage was intermediate and advanced stage in 1 (6.3%) and 15 patients (93.8%), respectively. The serum α-fetoprotein at baseline was 4,911 (IQR 2,091–17,377) ng/mL. The disease control rate in patients with mALBI grade1 + 2a was significantly higher than in those with mALBI grade 2b (100 vs. 28.6%, <i>p</i> = 0.028). The patients with mALBI grade 1 + 2a had a significantly better overall survival (OS) and longer progression-free survival (PFS) than those with mALBI grade 2b (median OS 6.7 vs. 3.0 months; <i>p</i> = 0.036, median PFS 7.5 vs. 1.4 months; <i>p</i> = 0.002). The number of cycles of ramucirumab treatment was significantly correlated with the ALBI score (<i>r</i> = −0.452, <i>p</i> = 0.030). The patients with mALBI grade 1 + 2a showed a low incidence of adverse events (AEs) and discontinuation due to AEs. <b><i>Conclusions:</i></b> Advanced HCC patients with mALBI grade 1 + 2a may be a good indication for ramucirumab treatment.

scholarly journals Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: a subgroup analysis of the phase 3 KEYNOTE-045 trial

2019 ◽  
Vol 25 (1) ◽  
pp. 165-174 ◽  
Author(s):  
Hiroyuki Nishiyama ◽  
Yoshiaki Yamamoto ◽  
Naoto Sassa ◽  
Kazuo Nishimura ◽  
Kiyohide Fujimoto ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Open Label ◽  
End Points ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

Abstract Background The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan. Patients and methods Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points. Results Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44–1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32–1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95–3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3–5 events, occurred less frequently with pembrolizumab. Conclusions Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.

scholarly journals The neutrophil-lymphocyte ratio has a role in predicting the effectiveness of nivolumab in Japanese patients with metastatic renal cell carcinoma: A multi-institutional retrospective study

2019 ◽  
Author(s):  
Naotaka Nishiyama ◽  
Megumi Hirobe ◽  
Takuya Kikushima ◽  
Masahiro Matsuki ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Japanese Patients ◽  
Free Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Initiation Of Therapy ◽  
Better Than

Abstract Background: The neutrophil-lymphocyte ratio (NLR) is a well-known prognostic marker in various cancers. However, its role as a predictive marker for the effectiveness of nivolumab in patients with metastatic RCC (mRCC) remains unclear. We evaluated the relationships between the NLR and progression-free survival (PFS) or overall survival (OS) in mRCC patients treated with nivolumab. Methods: The data of 46 mRCC patients who received nivolumab therapy were collected from six institutes and evaluated. The median follow-up period from treatment with nivolumab was 12.5 months (IQR 10.0-16.7). Results: The median duration of nivolumab therapy was 6.5 months (IQR 3.3-13.7). The objective response rate was 22% and the 1- and 2-year PFS rates were 49.4% and 34.8%, respectively. The median NLR values at baseline and 4 weeks were 3.7 (IQR 2.7-5.2) and 3.7 (IQR 2.5-5.9), respectively. In the multivariate analysis, an NLR of ≥ 3 at 4 weeks was an independent predictor of PFS (P = 0.005) and OS (P = 0.031). The 1-year PFS of patients with an NLR of < 3 at 4 weeks was better than that of those with an NLR of ≥ 3 (83% versus 27%, P = 0.001). The 1-year OS of patients with an NLR of < 3 at 4 weeks was also better than that of those with an NLR of ≥ 3 (94% versus 71%, P = 0.002). Conclusions: Although the baseline NLR was not associated with PFS or OS, an NLR of ≥3 at 4 weeks after the initiation of therapy might be a robust predictor of poor PFS and OS in mRCC patients undergoing sequential treatment with nivolumab.

scholarly journals REFLECT—a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset

2019 ◽  
Vol 55 (1) ◽  
pp. 113-122 ◽  
Author(s):  
Tatsuya Yamashita ◽  
Masatoshi Kudo ◽  
Kenji Ikeda ◽  
Namiki Izumi ◽  
Ryosuke Tateishi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Japanese Population ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Unresectable Hepatocellular Carcinoma

Abstract Background A phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority [OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79–1.06], and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported. Methods The intent-to-treat population enrolled in Japan was analyzed. Results Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (N = 81) or the SOR arm (N = 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR (HR 0.90; 95% CI 0.62–1.29). LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm. Conclusions The efficacy and safety of LEN in the Japanese population were similar to those in the overall population of REFLECT. With manageable adverse events, LEN is a new treatment option for Japanese patients with uHCC. Trial registration ID ClinicalTrials.gov. No. NCT01761266.

scholarly journals On-Treatment Albumin-Bilirubin Grade: Predictor of Response and Outcome of Sorafenib-Regorafenib Sequential Therapy in Patients with Unresectable Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3758
Author(s):  
Hung-Wei Wang ◽  
Po-Heng Chuang ◽  
Wen-Pang Su ◽  
Jung-Ta Kao ◽  
Wei-Fan Hsu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Control ◽  
Median Overall Survival ◽  
Cox Regression ◽  
Independent Predictor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival

In the RESORCE study, regorafenib after sorafenib therapy improved survival in patients with advanced hepatocellular carcinoma (HCC). In total, 88 patients with unresectable HCC who received sorafenib–regorafenib sequential therapy were enrolled. The objective response rate and disease control rate were 19.3% and 48.9%, respectively, for regorafenib therapy (median duration: 8.1 months). Median progression-free survival (PFS) after regorafenib therapy was 4.2 months (95% CI: 3.2–5.1). The median overall survival (OS; from initiation of either sorafenib or regorafenib) was not reached in this cohort. According to multivariate Cox regression analyses, albumin-bilirubin (ALBI) grade at the initiation of regorafenib therapy is an independent predictor of disease control, PFS, and OS. Moreover, the combination of ALBI grade 2 and an alpha-fetoprotein (AFP) level of ≥20 ng/mL was an independent predictor of PFS (hazard ratio (HR): 3.088, 95% CI: 1.704–5.595; p < 0.001) for regorafenib therapy, and OS for both regorafenib (HR: 3.783, 95% CI: 1.316–10.88; p = 0.014) and sorafenib–regorafenib sequential (HR: 4.603, 95% CI: 1.386–15.29; p = 0.013) therapy. A combination of ALBI grade and AFP level can be used to stratify patients with unresectable HCC by PFS and OS probability for sorafenib–regorafenib sequential therapy.

scholarly journals Relative Dose Intensity of Induction-Phase Pazopanib Treatment of Soft Tissue Sarcoma: Its Relationship with Prognoses of Pazopanib Responders

2019 ◽  
Vol 8 (1) ◽  
pp. 60 ◽  
Author(s):  
Kenji Nakano ◽  
Yuki Funauchi ◽  
Keiko Hayakawa ◽  
Taisuke Tanizawa ◽  
Keisuke Ae ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Liver Toxicity ◽  
Standard Dose ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Relative Dose Intensity ◽  
Induction Phase ◽  
Free Survival

The approved standard dose of pazopanib is 800 mg per day, but the appropriate dose of pazopanib to treat soft tissue sarcoma (STS) patients in real-world practice is controversial. Of 124 STS patients treated with pazopanib, we retrospectively analyzed the cases of STS patients who achieved progression-free survival at 12 weeks by pazopanib treatment as pazopanib responders, and we evaluated their relative dose intensity (RDI) in the initial 12 weeks (12W-RDI). We enrolled 78 STS patients in the analyses as pazopanib responders, and 54 patients of the 78 pazopanib responders (69%) were able to maintain 12W-RDI ≥80%. In landmark analyses, patients with 12W-RDI of 80% ≥80% had significantly longer progression-free survival compared to those with 12W-RDI <80% (30.7 weeks vs. 22.0 weeks, hazard ratio [HR]: 0.56 [95%CI: 0.33–0.94], p = 0.026). The most frequently observed reasons of treatment interruption and/or dose reduction of pazopanib during the initial 12 weeks were anorexia and liver function disorders. Liver toxicity was the adverse event most frequently observed in the 12W-RDI <80% patients throughout the treatment periods. Based on our results, it appears that maintaining as high a dose intensity as possible that is tolerable—at least during the initial 12 weeks—is likely to be the better option in pazopanib treatment for STS patients.

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