scholarly journals Paradigm Shifting of Systemic Chemotherapy for Unresectable Pancreatic Cancer in Japan

2019 ◽  
Vol 8 (8) ◽  
pp. 1170 ◽  
Author(s):  
Junji Furuse
Keyword(s):  
Pancreatic Cancer ◽  
Systemic Chemotherapy ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Phase Iii ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Brca Mutations ◽  
Line Chemotherapy

Systemic chemotherapy plays an important role in the treatment of pancreatic cancer, to improve the survival of patients with pancreatic cancer. Unresectable pancreatic cancer can be classified into three categories: metastatic, locally advanced, and hereditary pancreatic cancers. Furthermore, the second-line chemotherapy is required to prolong the survival. The combined regimens of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GEM plus nab-PTX) have been recognized as the standard of care for advanced pancreatic cancer. However, the consensus of selection of the first-line chemotherapy still remains. Randomized controlled trials (RCTs) between FOLFIRINOX and GEM plus nab-PTX are ongoing for locally advanced and metastatic disease in Japan, respectively. Hereditary pancreatic cancer, especially associated with BRCA mutations, is responsive to platinum-containing regimens and/or poly (ADP-ribose) polymerase (PARP) inhibitors. It is becoming more important to examine the presence/absence of BRCA mutations to select the appropriate treatment strategy for individual patients. Although some S-1-based regimens have been investigated in the second-line treatment after GEM-based chemotherapy in Japan, no regime demonstrated survival benefit. Nanoliposomal irinotecan (nal-IRI) plus FF has been established as the standard of care in the second-line treatment in a global phase III trial (NAPOLI-1). A randomized phase II trial comparing FF plus nal-IRI with FF alone was also conducted in Japan to examine the efficacy and safety of the FF plus nal-IRI in Japanese patients.

Efficacy of S-1 compared to modified FOLFIRINOX as second-line chemotherapy regimens after gemcitabine plus nab-paclitaxel for patients with metastatic pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 449-449 ◽  
Author(s):  
Gen Kimura ◽  
Hideaki Takahashi ◽  
Kumiko Umemoto ◽  
Kazuo Watanabe ◽  
Mitsuhito Sasaki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chemotherapy Regimen ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Clinical Records ◽  
Line Chemotherapy

449 Background: Recently, gemcitabine (GEM) plus nab-paclitaxel (nab-PTX) has been frequently used as a first-line chemotherapy regimen for the treatment of metastatic pancreatic cancer (mPC) in Japan. Nanoliposomal irinotecan combined with 5-fluorouracil and leucovorin (MM-398 plus 5FU/LV) has not yet been approved in Japan. Under these circumstances, a modified FOLFIRINOX (mFFX) regimen or S-1 is commonly used as a second-line chemotherapy regimen for patients with mPC after GEM plus nab-PTX has failed. Methods: Between December 2014 and March 2016, 45 patients with mPC received second-line chemotherapy after the failure of GEM plus nab-PTX (standard dose regimen) at the National Cancer Center Hospital East. Twenty-two patients received mFFX (irinotecan, 150 mg/m2; bolus of 5FU was eliminated), 19 received S-1 (80 mg/m2/d; d1-28, q6w or d1-14, q3w), and 4 received other chemotherapy regimens. The clinical records of the patients were reviewed retrospectively. Results: At baseline, S-1 group had a more severe disease status than the mFFX group (performance status of 0: 21% vs. 68%, P = 0.003; median CA19-9 level: 1832 vs. 577 U/mL, P = 0.30). No significant difference in the response rate (S-1, 5.3% vs. mFFX, 9.1%, P = 0.56) or the disease control rate (S-1, 42% vs. mFFX, 36%, P = 0.71) was seen between the two groups. The progression free survival (PFS) (median: S-1 vs. mFFX: 2.7 vs. 2.4 months (m), P = 0.77), the overall survival (OS) from the second-line treatment (median: 6.1 vs. 6.4m, P = 0.87) and the OS from the first-line treatment (median: 10.9 vs. 12.4m, P = 0.77) were not significantly different between the two groups. These results were similar to those observed for MM-398 plus 5FU/LV (PFS, 3.1m; OS, 6.1m) in a pivotal Phase III study (NAPOLI-1). The incidences of peripheral neuropathy (5.3% vs. 32%, P = 0.04), fatigue (11% vs. 50%, P = 0.007), and neutropenia (11% vs. 64%, P = 0.001) were significantly lower in the S-1 group. Conclusions: S-1 was less toxic than mFFX and exerted a similar anti-tumor effect in the present study. S-1 could be a treatment option for patients with mPC refractory to GEM plus nab-PTX.

scholarly journals FOLFIRINOX after first-line gemcitabine-based chemotherapy in advanced pancreatic cancer: a retrospective comparison with FOLFOX and FOLFIRI schedules

2020 ◽  
Vol 12 ◽  
pp. 175883592094797
Author(s):  
Francesca Foschini ◽  
Fabiana Napolitano ◽  
Alberto Servetto ◽  
Roberta Marciano ◽  
Eleonora Mozzillo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Optimal Sequence ◽  
Line Chemotherapy

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks ( p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

Efficacy of cetuximab after immunotherapy (IO) in advanced cutaneous squamous cell carcinoma (CSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9562-9562
Author(s):  
Julian Andres Marin-Acevedo ◽  
Bethany Withycombe ◽  
Youngchul Kim ◽  
Zeynep Eroglu ◽  
Joseph Markowitz ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Acquired Resistance ◽  
Standard Of Care ◽  
Line Treatment ◽  
Second Line ◽  
Survival Times ◽  
Entire Cohort ◽  
Overall Response ◽  
Curative Radiotherapy

9562 Background: Anti-PD1 (aPD1) monotherapy with cemiplimab-rwlc or pembrolizumab is now considered standard of care for first-line management of advanced CSCC not amenable to surgery or curative radiotherapy. Previously chemotherapy or anti-EGFR agents were commonly used for these patients albeit with modest efficacy and limited duration of response. In prospective evaluation, the overall response rate (ORR) to cetuximab was 28% with disease control rate (DCR) of 69% at 6 weeks. The efficacy of second-line treatment following primary or acquired resistance to aPD1 therapy is not known. We investigated the activity of cetuximab in patients who progressed on previous IO therapy. Methods: We performed a single institution retrospective review from 9/28/18 (US approval date of cemiplimab-rwlc for CSCC) through 11/30/20 of patients with locally advanced or metastatic CSCC who received cetuximab after prior IO therapy. We identified patients who received cetuximab either immediately following IO therapy (cohort A) or as a subsequent line not immediately following IO therapy (cohort B). Primary endpoint was ORR with secondary endpoints of DCR, survival and toxicity. Median follow-up and survival times were calculated using the Kaplan-Meier method. Results: Thirteen patients, median age 72 years (62-82), all Caucasian, and 11 males (85%) were included in this study. Eleven pts received cetuximab immediately post-IO progression; two had additional intervening therapy post-IO before receiving cetuximab. Three patients received concurrent radiotherapy (palliative or definitive) with cetuximab. The ORR to cetuximab was 54% (7/13) including 1 complete and 6 partial responses. The cumulative 6-month DCR was 77%. All responses were observed in cohort A; both patients in cohort B had progressive disease as best response. Six of 7 initial responses are ongoing, including 3 in whom cetuximab was discontinued. At a median follow-up of 9.1 months, the median PFS has not been reached for the entire cohort. There were no unanticipated toxicities to cetuximab with rash (77%) and hypomagnesemia (54%) being the most common adverse events. Conclusions: In advanced CSCC, cetuximab used immediately after progression on aPD1 therapy yields notably higher and durable overall response than previously reported in the pre-IO therapy era. If validated in a larger dataset, this should be the preferred therapy for second-line treatment in advanced CSCC. Further exploration into the mechanism of this high efficacy of anti-EGFR therapy post aPD1 therapy is warranted.

Irinotecan in the Treatment of Colorectal Cancer: Clinical Overview

2001 ◽  
Vol 19 (5) ◽  
pp. 1501-1518 ◽  
Author(s):  
Udo Vanhoefer ◽  
Andreas Harstrick ◽  
Wolf Achterrath ◽  
Shousong Cao ◽  
Siegfried Seeber ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Topoisomerase I ◽  
Clinical Status ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Phase Iii Trials ◽  
Line Chemotherapy

PURPOSE AND METHODS: For more than three decades, the therapeutic options for patients with advanced colorectal cancer have almost exclusively been based on fluoropyrimidines. With the recognition that topoisomerase-I (TOP-I) is an important therapeutic target in cancer therapy, irinotecan, a semisynthetic TOP-I–interactive camptothecin derivative, has been clinically established in the treatment of colorectal cancer. RESULTS: Irinotecan was investigated as second-line chemotherapy after prior treatment with fluorouracil (FU)-based regimens in two large randomized phase III trials comparing irinotecan with either best supportive care or an infusional FU/leucovorin (LV) regimen. The outcomes of these trials established irinotecan as the standard therapy in the second-line treatment of colorectal cancer. The therapeutic value of irinotecan in the first-line treatment of metastatic colorectal cancer was investigated in two large randomized phase III trials comparing the combination of irinotecan and FU/LV with FU/LV alone. Both trials demonstrated significant superior efficacy for the combination of irinotecan and FU/LV in terms of response rate, median time to disease progression, and median survival time. Consequently, the combination of irinotecan and FU/LV has been approved as first-line chemotherapy for patients with metastatic colorectal cancer and constitutes the reference therapy against which other treatment options must be tested in the future. CONCLUSION: In this review, the clinical rationale and update of the present clinical status of irinotecan in the treatment of colorectal cancer and future prospects of irinotecan-based combinations are discussed.

Nonstandard first-line therapy and survival in patients (pts) with recurrent/metastatic head and neck cancer (RMHNSCC): Experience of 194 pts in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16036-e16036
Author(s):  
Jerome Fayette ◽  
Valentine Polivka ◽  
Sylvie Chabaud ◽  
Bertrand Favier ◽  
Severine Racadot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Alternative Therapy ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Phase Iii Studies ◽  
Line Chemotherapy

e16036 Background: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Methods: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Results: At initiation of palliative chemotherapy, median age was 62 [29-87]; PS was 0, 1, 2, 3 in 13%, 59%, 16% and 11% of pts, respectively. First line chemotherapy consists in combination cisplatin+taxanes (CIST) 24%, caboplatin+taxanes (CART) 33%, cisplatin or carboplatin without taxanes (NOT) 15% or others (OTH) 28%. Median OS was estimated to 9.6 months CI95%=[8.1-11.4], with 39% of pts; CI95%=[32-47] still alive at 1-year. Second line of treatment has been initiated in 61% of pts. Some of them have even been able to have up to 3, 4 or more than 4 lines of treatment in 19%, 11% and 4% of pts, respectively. In the subgroup analysis, which represents a population similar to those included in [ref1], first line chemotherapy was CIST, CART, NOT or OTH in 30%, 30%, 18% and 22%, respectively. Median OS was 13.0 months, CI95%=[11.2-17.7] reaching up to 15.3 months for CIST subgroup. Second line of treatment was initiated in 73% of pts, with 20%, 15% and 5% of pts having a third, a fourth, and a fifth line, respectively. Conclusions: We can reach for unselected pts the best OS published in phase III studies. The use in first line of combination of platinum and taxanes, followed by monotherapies with cetuximab, capecitabine and methotrexate allows reaching OS of 13 months.

Activity and survival benefit of second-line chemotherapy (2L-Ctx) in advanced pancreatic adenocarcinoma (APC): Pooled analysis of the literature.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15019-e15019 ◽  
Author(s):  
MinYuen Teo ◽  
Raymond S. McDermott
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Survival Benefit ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Line Setting ◽  
Line Chemotherapy

e15019 Background: Many clinicians adopt a nihilistic approach to the management of APC. Delivery of 2L-Ctx is relatively uncommon and no recognized standard exists. We sought to examine the published activity of chemotherapy in the 2nd line setting, and the rate of 2L-Ctx delivery and its influence on reported overall survival in 1st line trials. Methods: 1st and 2L-Ctx randomized trials published between 2000 and 2012 were identified from Pubmed, and manuscripts were obtained for data extraction. Pooled weighted objective response rates (ORR) and disease control rates (DCR) were calculated. For 1st line studies, the percentage of patients who received 2L-Ctx were extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Spearman correlation and linear regression were performed. Results: Sixty nine 2L Ctx studies (77 arms, n=2859) were identified. Majority received prior gemcitabine-based chemotherapy. Pooled ORR was 6.6% (95% CI 5.6 – 7.6%) and DCR was 36.7% (34.5 – 38.0%). When only prospective studies were evaluated (42 studies, 48 arms, n=1546), ORR was 5.0% (3.8 – 6.2%) and DCR was 33.9% (31.0 – 36.9%). Exploratory analysis suggested that intensification of gemcitabine-based therapy (ORR: 10.0%; DCR: 54.7%) might be marginally more active than fluoropyrimidine (7.6%; 32.2%) or taxane based 2L-Ctx (5.2%; 33.6%). 28/52 identified 1st line studies (54%) reported the percentage of patients treated with second-line chemotherapy (11 phase II, 28 arms, n=1450; 17 phase III, 33 arms, n=5051). Percentage of 2L-Ctx delivery ranged from 14 – 68% and correlated with OS (r=.49 [.26 – .67], p<.01) and PPS (r=.57 [.36 – .72], p<.01). When phase II studies were excluded, correlation was improved for OS (r=.63 [.35 – .81], p<.01) and PPS (r=.79 [.59 – .89], p<.01). Percentage of locally advanced disease did not correlate with OS/PPS nor affect prior analysis. Conclusions: Whilst awaiting further advancement in the 1st line setting, increased delivery of 2L-Ctx to patients with APC and maintained performance status may offer a survival benefit.

Efficacy and safety of paclitaxel/ramucirumab as the second-line chemotherapy in Japanese patients with advanced gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15540-e15540
Author(s):  
Tetsuya Kusumoto ◽  
Akinori Egashira ◽  
Hideto Sonoda ◽  
Kenkichi Hashimoto ◽  
Hideo Uehara ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Japanese Patients ◽  
Phase Iii ◽  
Weekly Dose ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

e15540 Background: Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer (AGC). Two global randomized phase III trials (REGARD and RAINBOW) showed that survival benefit was significantly observed in patients treated with ramucirumab (RAM) alone and in combination with weekly doses of PTX, compared with placebo, respectively. The purpose of the study is to evaluate the efficacy and safety of weekly dose of PTX combined with RAM practically as the second-line treatment in Japanese patients with AGC refractory to an S-1-containing chemotherapy regimen. Methods: We conducted a retrospective review of the data of 18 patients with AGC who received more than 2 cycles of PTX/RAM combined chemotherapy as the second-line regimen following S-1-based treatment. The objective response rate (ORR), adverse events, progression-free survival (PFS) and overall survival (OS) were analyzed and compared with PTX monotherapy group. Results: Median number of courses were 5 for the PTX/RAM group and the discontinuation of treatment except for disease progression was found in 2 cases (33.3%). The rates of hematological toxicities of higher than grade 3 were 33.3% in the PTX/RAM group, which were higher than those found in the PTX groups. The tumor responses of the PTX/RAM group were 22% for the ORR and 78% for the DCR, compared with 21% and 48% in the PTX group, respectively. The dose intensities of PTX were 72.4% in the former group. The survival data showed that the MST after second-line exposure was 290 days and the median PFS was 131 days in the PTX/RAM group, compared with 159 days and 90 days in the PTX group, which were not significantly different. Conclusions: PTX/RAM might be one of the best regimens for Japanese patients with AGC as the second-line treatment following S-1-containing chemotherapy.

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