A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3595-3595
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Heavily Pretreated

3595 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with fluoropyrimidines-, oxaliplatin- and irinotecan-containing regimens. Methods: 36 pts were enrolled, with the following characteristics: 19 females (53%), median age 57 (28-72), 30 EOGO PS 0-1 (83%). S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was 5 (range 1-9), ORR was 16.7% (95% confidence interval [CI] 4.5-28.9%) and disease control rate was 61.1% (95% CI 45.2-77.0%) with 6 partial responses and 16 stable diseases. Median duration of disease control was 5.8 months (95% CI 4.1-7.5 months). Median progression-free survival was 3.7 months (95% CI 2.2-5.2 months) and median overall survival was 10.0 months (95% CI 7.4-12.7 months). Grade 3-4 toxicities were rare (neutropenia 12%, anemia 11%, leucopenia 6%, thrombocytopenia 3% and diarrhea 3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was a convenient, well tolerated and efficacious for heavily pre-treated pts with mCRC. This regimen warrants further evaluation in pts with good PS but no further treatment options.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 488-488 ◽  
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Ps

488 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin and irinotecan. Methods: 34 pts were enrolled, with the following characteristics: 17 (50%) females, median age 57 years (28-72), 28 (82%) ECOG PS 0-1. S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). ORR was 14.7% (95% confidence interval [CI] 2.8-26.6) and disease control rate was 58.8% (95% CI 42.2-75.3) with five partial responses and fifteen stable diseases. Median duration of disease control was 5.1 months (95% CI 3.3-7.0). Median progression-free survival was 3.2 months (95% CI 2.3-4.1) and median overall survival was 11.8 months (95% CI 7.0-16.5). Grade 3-4 toxicities were neutropenia (12%), anemia (12%), thrombocytopenia (3%) and diarrhea (3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for heavily pre-treated mCRC pts, and could be an alternative for pts with good PS but no further treatment options.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14137-e14137
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Minkyu Jung ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Heavily Pretreated ◽  
Number Of Cycles

e14137 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil, oxaliplatin and irinotecan. Methods: Between Dec 2009 and Nov 2011, 23 pts were enrolled, with the following characteristics: 12 males and 11 females, median age 57 years (28-72). S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). OR was 8.7% (95% confidence interval [CI] 0-20.2) and disease control rate was 56.5% (95% CI 36.4-76.9) with two partial responses and eleven stable diseases. Median duration of disease control was 8.5 months (95% CI 3.8-13.2). Median progression-free survival was 3.2 months (95% CI 1.9-4.5) and median overall survival was 11.8 months (95% CI 4.0-19.5). Grade 3-4 toxicities were neutropenia (8%) and thrombocytopenia (4%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for refractory mCRC pts.

A randomized phase II non-comparative study of Ispinesib given weekly or every three weeks in metastatic colorectal cancer. A California Cancer Consortium Study (CCC-P)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3595-3595 ◽  
Author(s):  
A. B. El-Khoueiry ◽  
S. Iqbal ◽  
D. A. Singh ◽  
S. D’Andre ◽  
R. K. Ramanathan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Median Number ◽  
Primary Objective ◽  
Significant Activity ◽  
Heavily Pretreated ◽  
And Function

3595 Background: Ispinesib(SB-715992) is a polycyclic, nitrogen-containing heterocycle that inhibits the mitotic kinesin spindle protein (KSP). KSP is essential for mitotic spindle assembly and function during mitosis, and is a rational target of anti-cancer therapy. This phase II study used two different dosing schedules; the primary objective was to determine the response rate (RR) and the secondary objectives were to determine time to tumor progression (TTP), progression free survival (PFS), overall survival (OS) and toxicity. Methods: Patients (pts) were randomized to receive (Arm A) ispinesib 7 mg/m2 every week for 3 weeks, every 28 days or (Arm B) 18 mg/m2 every 21 days. Response was assessed every 6 weeks. Chemotherapy was administered until disease progression or intolerance. Results: A total of 64 pts were accrued. The median number of cycles was 2 for both arms. Five pts had stable disease and 48 had progressive disease. PFS was 49 days in Arm A (44 to 51) and 37 days in Arm B (35 to 42 days). The most common grade 3/4 toxicities in arms A and B respectively included neutropenia (3 and 20), nausea and vomiting (3 and 1), neurologic (1 and 2). Of these, only 1 pt had febrile neutropenia and 1 pt had peripheral sensory neuropathy. The toxicity data is not available on 2 patients. Eleven pts are not evaluable for response yet. Conclusions: Ispinesib did not demonstrate significant activity in heavily pretreated patients with advanced/metastatic colorectal cancer at the dose and schedule employed in this trial. Correlative studies are in progress. Supported by NO1 CM17101 [Table: see text] No significant financial relationships to disclose.

Sorafenib and irinotecan combination for pre-treated RAS-mutated metastatic colorectal cancer patients: A multicentre randomized phase II trial (NEXIRI 2).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 635-635 ◽  
Author(s):  
Emmanuelle Samalin ◽  
Christelle De La Fouchardiere ◽  
Simon Thezenas ◽  
Valérie Boige ◽  
Hélène Senellart ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Fixed Dose ◽  
Randomized Phase Ii ◽  
Heavily Pretreated ◽  
Colorectal Cancer Patients

635 Background: Sorafenib and irinotecan (NEXIRI regimen) showed promising activity with a disease control rate (DCR) of 65% in heavily pretreated mutated (mt) KRAS metastatic colorectal cancer (mCRC) patients in a phase I/II trial (Samalin et al. 2014).This multicentre randomized phase II trial aimed to determine the 2-month progression-free survival rate (2-PFS) of NEXIRI versus irinotecan or sorafenib monotherapy in mtRAS mCRC patients after failure of all approved active drugs at the time of the study. Methods: Patients PS ≤ 1 with progressive measurable and non-resectable mtKRAS (then RAS) mCRC pre-treated with irinotecan, oxaliplatin, fluoropyrimidines and bevacizumab (none regorafenib), were randomized in 3 arms: NEXIRI (irinotecan IV 120 (C1), 150 (C2) and 180mg/m² (C3) if diarrhea grade < 1 in a biweekly regimen combined with a fixed dose of sorafenib, 400mg twice daily) versus irinotecan alone (180mg/m²) versus sorafenib alone until progression or toxicity, with cross over to NEXIRI at progression for the monotherapy arms. The primary endpoint was the 2-PFS (RECIST v1.1). Pharmacokinetic, pharmacogenetics and pathologic translational studies were undertaken. Results: We included 173 patients (median age 62 [31-82]; PS 0/1: 38/61%) between 2012/09 and 2014/07 in 17 French centres. Main results are shown below (median follow-up 17.5 months). Conclusions: We confirmed the NEXIRI regimen efficacy in a randomized study for refractory mtRAS mCRC patients. These results justify comparing this combination to regorafenib or TAS 102 monotherapies in this population. Ancillary studies are ongoing to identify biomarkers. Clinical trial information: NCT01715441. [Table: see text]

Phase II trial of oral S-1 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard chemotherapies (CCOG-1105 study).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 841-841
Author(s):  
Kazuhiro Ezaka ◽  
Goro Nakayama ◽  
Hiroyuki Yokoyama ◽  
Takanori Matsui ◽  
Shinichi Umeda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Median Number ◽  
Mutant Type ◽  
Number Of Treatment

841 Background: The aim of this multicenter, single-arm phase II trial was to investigate the efficacy and safety of S-1 plus bevacizumab (BEV) as a salvage treatment for patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapies. Methods: Patients who had unresectable mCRC with mutant-type KRAS; were refractory to fluoropyrimidine, irinotecan, oxaliplatin; and had previous treatment with BEV were enrolled and received S-1 plus BEV therapy (bevacizumab 7.5 mg/kg on day 1 and S-1 40-60 mg bid on day 1-14, every 3 weeks). The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), tumor response, and safety. Results: A total of 27 patients were enrolled. After a median follow-up period of 12.3 months, the events of disease progression and death occurred in 26 patients (96%) and 20patients (74%), respectively. The median number of treatment cycles was 3 (range, 1-17 cycles). Median PFS was 2.3 months (95% confidence interval [CI], 2.2-2.4 months), and the median OS was 7.7 months (95% CI, 4.3-10.1 months). The overall response and disease control rates were 0% and 33%, respectively. The median tumor shrinkage rate (DpR) was -15% (range, -59 to 15%). The frequencies of hematological and non-hematological adverse events above grade three were 25% and 8%, respectively. Conclusions: S-1 plus BEV therapy could be feasible salvage line treatment for Japanese patients with mCRC refractory to standard chemotherapies. Clinical trial information: UMIN000006476.

Retreatment of Irinotecan in Later Lines of Therapy for Metastatic Colorectal Cancer: A Retrospective Study

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Moon Ki Choi ◽  
Yongjun Cha ◽  
Ji Yeon Baek
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Epidermal Growth ◽  
Grade 3

<b><i>Background:</i></b> Due to few efficacious options in later lines of therapy in metastatic colorectal cancer (mCRC), there has been considerable interest in the possibility of retreatment with previously administered agents. This study investigated the efficacy and safety of irinotecan retreatment (IRI2) in patients with refractory mCRC. <b><i>Methods:</i></b> We performed a retrospective analysis of patients with mCRC who were retreated with irinotecan-based regimens. The retreatment regimens with anti-epidermal growth factor receptor therapies were excluded. <b><i>Results:</i></b> A total of 64 patients were included. Patients had a median age of 56 years and were offered mainly in the setting of third- or fourth-line therapy with IRI2. The disease control rate was 78.2% including an objective response of 23.5%. Median progression-free survival and overall survival were 5.5 and 19.3 months, respectively. The most frequent grade 3 or higher toxicities were nausea/vomiting (27.9%) and neutropenia (25%). <b><i>Conclusion:</i></b> IRI2 might be a reasonable option for heavily pretreated patients with mCRC who achieved disease control with prior irinotecan therapy.

Phase II Trial of Chronomodulated Infusion of High-Dose Fluorouracil and l-Folinic Acid in Previously Untreated Patients With Metastatic Colorectal Cancer

2002 ◽  
Vol 20 (5) ◽  
pp. 1175-1181 ◽  
Author(s):  
H. Curé ◽  
V. Chevalier ◽  
A. Adenis ◽  
N. Tubiana-Mathieu ◽  
G. Niezgodzki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
World Health ◽  
Fixed Dose ◽  
High Dose

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status ≤ 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 pm to 10:00 am with peak at 4:00 am). 5-FU dose was escalated from 900 to 1,100 mg/m2/d with fixed dose of l-FA at 150 mg/m2/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

Intravenous weekly high-dose infusion of 5-fluorouracil and folinic acid in previously heavily pretreated patients with metastatic colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 766-766
Author(s):  
Gudrun Piringer ◽  
Verena Huber ◽  
Sonja Burgstaller ◽  
Martin Weninger ◽  
Andreas Karrer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Retrospective Analysis ◽  
Progression Free Survival ◽  
Median Number ◽  
High Dose ◽  
Dose Infusion ◽  
Heavily Pretreated ◽  
Pretreated Patients

766 Background: Patients with metastatic colorectal cancer (CRC) usually receive multiple lines of treatment. Using a present day standard 1st line chemotherapy combination a progression free survival in the range of 8-12 months can be obtained. With consecutive treatment lines the median survival has now exceeded the 2-year landmark. In case of disease progression after two or more lines of treatment, the survival is about 4-6 months with best supportive care alone. However, some patients are still able and willing to receive further therapy. In the present retrospective analysis the efficacy of a weekly intravenous high-dose infusion of 5-Fluorouracil and folinic acid in heavily pretreated patients with metastatic CRC beyond the standard chemotherapy lines was evaluated. Methods: The Klinikum Wels-Grieskirchen collects data on all CRC patients since July 2006 in a clinical tumor registry. In this retrospective analysis pretreated CRC patients that were treated with the Ardalan-regimen (500mg/m2 folinic acid as 1 hour infusion followed by 2.600mg/m25-Fluorouracil as 24-hour infusion) have been evaluated. Results: A total of 23 evaluable patients with a median age of 66 years received the Ardalan-regimen as 2nd (4.4%), 3rd (13%), 4th (13%), 5th (52.2%), 6th (4.4%) or 7th (13%) line treatment. The median number of cycles received was 9 (range 2-18) and the Ardalan-regimen was started within 13-56 months (median 26 months) after the diagnosis of metastatic disease. Fourteen (60.9%) and nine (39.1%) out of these patients were women and men, respectively. 60.9% (14 patients) had a tumor located in the colon and 39.1% had rectal cancer. 17.4% of patients had stable disease and 65.2% of patients had progressive disease after 3 months of therapy. In 4 patients response according to RECIST criteria was not evaluable. Median overall survival since the start of the Ardalan-regimen was 6.7 months. Conclusions: Patients with advanced metastatic CRC can be candidates for multiple lines of therapy. In previously heavily pretreated patients, the Ardalan-regimen is able to control the disease in a limited proportion of patients.

151 A RANDOMIZED,OPEN CLINICAL TRIAL TO COMPARE THE EFFICACY AND SAFETY OF ANLOTINIB PLUS IRINOTECAN VERSUS IRINOTECAN IN PATIENTS WITH ESCC

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Xiangrui Meng ◽  
Hangrui Liu ◽  
Qingxia Fan
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Thyroid Stimulating Hormone ◽  
Disease Control Rate ◽  
Control Group ◽  
Trial Group ◽  
Grade 3

Abstract   The benefit of systemic treatment in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain. Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferation. A phase II trial (NCT02649361) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in refractory metastatic ESCC. This study (NCT03387904) aimed at comparing the effects and safety of Anlotinib Plus Irinotecan versus Irinotecan in patients with ESCC. Methods We conducted a prospective randomized, multicenter, phase II trial to compare the efficacy of Anlotinib Plus Irinotecan with Irinotecan in recurrent ESCC patients who had resistance to platinum or taxane-based chemotherapy. Eligible patients were adults with pathologically confirmed recurrent ESCC, and 82 patients were randomized 1:1 to Irinotecan (65 mg/m2/day 1 and day 8) with or without anlotinib (12 mg qd day 1 to 14) of a 21-day cycle till progression or intolerable. The primary endpoint is the disease control rate (DCR) and progression-free survival (PFS) and the secondary end points are objective response rate (ORR) and overall survival (OS). Results Between 13/1 2019 and 20/1 2020, a total of 43 patients were enrolled and randomly assigned to either the anlotinib plus irinotecan (n = 22) or the irinotecan group (n = 21).The mPFS was longer in trial group than in control group (89 days vs 66 days, HR = 0.447, P = 0.055). The Disease control rate (DCR) was 54.5% in trial group and 38.1% in the control group. The treatment-related adverse events (&gt;10%) were fatigue (59.1%), nausea (50.0%), decreased appetite (36.4%), hoarseness (27.3%), thyroid-stimulating hormone elevation (22.7%), diarrhea (9.1%), and decreased lymphocytes count(9.1%) in trial group. Grade 3 AEs included fatigue (4.5% vs 4.8%), nausea (4.5% vs 0%) and diarrhea (4.5% vs 0%) in two groups. Conclusion Anlotinib plus irinotecan was similarly tolerable but prolonged PFS compared to irinotecan monotherapy as a second-line treatment in patients with recurrent ESCC.

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