scholarly journals Dual VEGF inhibition with sorafenib and bevacizumab as salvage therapy in metastatic colorectal cancer: results of the phase II North Central Cancer Treatment Group study N054C (Alliance)

2020 ◽  
Vol 12 ◽  
pp. 175883592091091 ◽  
Author(s):  
Hao Xie ◽  
Jacqueline M. Lafky ◽  
Bruce W. Morlan ◽  
Philip J. Stella ◽  
Shaker R. Dakhil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Salvage Therapy ◽  
Standard Therapy ◽  
Progression Free Survival ◽  
Heavily Pretreated ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Endothelial Growth Factor

Background: Bevacizumab (BEV), a monoclonal antibody against vascular endothelial growth factor-A (VEGF-A), is a standard component of medical therapy of metastatic colorectal cancer (mCRC). Activation of alternative angiogenesis pathways has been implicated in resistance to BEV. This phase II study examines the activity of combined vertical blockade of VEGF signaling with sorafenib and BEV as salvage therapy in patients with progressive disease (PD) on all standard therapy in mCRC. Methods: mCRC patients with documented PD on standard therapy, received sorafenib (200 mg orally twice daily, days 1–5 and 8–12) and BEV (5 mg/kg intravenously, day 1) every 2 weeks. Primary endpoint was 3-month progression-free survival (PFS) rate and secondary endpoints were overall survival (OS), response rate (RR), safety, and feasibility. Results: Of the 83 patients enrolled, 79 were evaluable. Of these, 42 (53%) were progression-free at 3 months. Median PFS was 3.5 months and median OS was 8.3 months. One patient had a partial response and 50 patients (63.3%) had at least one stable tumor assessment. Of 79 evaluable patients, 54 (68%) experienced grade 3/4 adverse events (AEs) at least possibly related to treatment. Most frequent grade 3/4 AEs were: fatigue (24.1%), hypertension (16.5%), elevated lipase (8.9%), hand-foot skin reaction (8.9%), diarrhea (7.6%), and proteinuria (7.6%). Reasons for treatment discontinuation were PD (72%), AEs (18%), patient refusal (8%), physician decision (1%), and death (1%). Conclusions: The combination of BEV and sorafenib as salvage therapy in heavily pretreated mCRC patients is tolerable and manageable, with evidence of promising activity. ClinicalTrials.gov identifier: NCT00826540, URL: http://clinicaltrials.gov/ct2/show/NCT00826540

Results of the Quad wild type arm of the AGITG ICECREAM study: A randomised phase II study of cetuximab alone or in combination with irinotecan in patients with refractory metastatic colorectal cancer with no mutations in KRAS, NRAS, BRAF or PIK3CA.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3572-3572 ◽  
Author(s):  
Jeremy David Shapiro ◽  
Subotheni Thavaneswaran ◽  
Craig Underhill ◽  
Kristy Pamela Robledo ◽  
Christos Stelios Karapetis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Wild Type ◽  
Response Characteristics ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

3572 Background: Cetuximab (cet) increases survival in RAS wild-type (WT) metastatic colorectal cancer (mCRC) in first-line and chemorefractory patients (pts). Adding irinotecan (iri) to cet in refractory pts who had progressed on iri increased response and delayed progression in the BOND trial, which was conducted prior to recognition that RAS mutations are predictive of EGFR-inhibitor (EGFR-I) resistance. Subsequent trials in chemorefractory pts used single agent EGFR-I as standard. In the era of biomarker selection, the benefit of continuing iri versus single agent EGFR-I had not been resolved. Methods: ICECREAM is a randomised phase II trial evaluating cet v cet + iri in chemotherapy-refractory mCRC, stratified for KRAS G13D mutation (previously reported) or no mutations in KRAS, NRAS, BRAF and PI3KCA (Quad WT ). EGFR-I naïve, ECOG PS 0-1 pts, progressing within 6 months of iri and refractory (or intolerant) to fluoropyrimidine and oxaliplatin were randomised to cet 400mg/m2 IV loading then 250mg/m2 weekly +/- iri 180mg/m2q2 wks. The primary endpoint was progression-free survival at 6 months (6m PFS); secondary endpoints were response rate (RR), overall survival (OS), toxicity and quality of life (QOL). Results: From Nov 2012 to June 2016, 48 Quad WT pts were recruited: 2 ineligible (not iri-refractory, BRAF mutation) wre not included for analyses and a further 2 not evaluable for response. Characteristics were balanced between cet (n = 21) v cet-iri (n = 25), except for sex (male 62 v 72%) and primary site (left 95 v 68%). 6m PFS rate was 14% v 41%; HR 0.39 (95% CI: 0.20–0.78, p = 0.008). RR was 10% (2 PR) v 36% (1 CR, 8 PR); p = 0.04. Toxicities were higher with cet-iri; at least one grade 3/4 adverse event in 50 v 23%. No differences in global or specific QOL were seen. Conclusions: The AGITG ICECREAM trial confirms a significant synergy for the addition of iri to cet and improved PFS in Quad WT chemorefractory mCRC, echoing data in molecularly unselected pts. Clinical trial information: ACTRN12612000901808.

A phase II trial of bevacizumab and capecitabine combination in metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14555-14555
Author(s):  
P. Zoran ◽  
D. Tarabar ◽  
R. Doder
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Drug Regimen ◽  
Survival Duration ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Third Line ◽  
Grade 3

14555 Background: This is a phase II study combination of capecitabine plus bevacizumab for patients with metastatic colorectal cancer after failure of both irinotecan- and oxaliplatin-containing regimens. Methods: The dose of capecitabine was 1000 mg/m2, administered twice daily for 14 days every 3 weeks. Bevacizumab was given at a dose of 5mg/kg on day 1 as i.v. infusion every 3 weeks. Treatment was repeated until the occurrence of disease progression or unaccepted toxicity. Results: Twenty-eight patients were enrolled. Of 28 patients, the overall response rate was 14.3% and the disease control rate was 42.9%. With a median follow-up period of 7 months, median time to progression and overall survival duration were 3 months and 14 months, respectively. The 1-year survival rate of all patients was 60.7%. The most common treatment-related grade 3/4 hematological toxicities included leukopenia/neutropenia in 4 patients and thrombocytopenia in 3 patients. Nonhematologic toxicities attributable to bevacizumab included bleeding in 3 patients, hypertension in 4 patients, thromboses in 3 patients, proteinuria in 5 patients, and gastrointestinal perforation in 1 patient. Conclusions: This drug regimen was well tolerated and combination of bevacizumab and capecitabine shows potential as third line chemotherapy in heavily pretreated patients with metastatic colorectal cancer. No significant financial relationships to disclose.

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.

scholarly journals Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer

2019 ◽  
Author(s):  
Daisuke Kotani ◽  
Yasutoshi Kuboki ◽  
Satoshi Horasawa ◽  
Asumi Kaneko ◽  
Yoshiaki Nakamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Task Force ◽  
Progression Free Survival ◽  
Clinical Settings ◽  
Monotherapy Group ◽  
Free Survival ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Previous Phase

Abstract Background: A previous phase I/II C-TASK FORCE study of trifluridine/tipiracil plus bevacizumab for patients with heavily pretreated metastatic colorectal cancer (mCRC) showed promising activity with an acceptable toxicity profile. This retrospective study aimed to investigate the safety and efficacy of trifluridine/tipiracil plus bevacizumab compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC in clinical settings. Methods: Records of patients with mCRC refractory to standard therapies who initiated trifluridine/tipiracil plus bevacizumab from January 2016 to March 2018 or trifluridine/tipiracil monotherapy from June 2014 to December 2015 were retrospectively reviewed at our institution. Results: Totally, 60 patients received trifluridine/tipiracil plus bevacizumab and 66 received trifluridine/tipiracil monotherapy. All patients had previously received standard chemotherapy. Median progression-free survival (PFS) was 3.7 months [95% confidence interval (CI), 2.3−5.1] in the trifluridine/tipiracil plus bevacizumab group and 2.2 months (95% CI, 1.8−2.6) in the trifluridine/tipiracil monotherapy group [hazards ratio (HR) 0.69; 95% CI 0.48−0.99]. PFS rate at 16 weeks was 46.6% for the trifluridine/tipiracil plus bevacizumab group and 33.9% for the trifluridine/tipiracil monotherapy group. Although a relatively higher incidence of grade ≥3 neutropenia was observed in the trifluridine/tipiracil plus bevacizumab group than that in the other group (50.0% vs. 40.9%, p = 0.371), the incidence of febrile neutropenia was not high (3.3% vs. 7.8%, p = 0.444). Conclusions: In real-world settings, trifluridine/tipiracil plus bevacizumab prolonged PFS and helped achieve higher 16-week PFS rate compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC with manageable toxicities. Trial registration: Retrospectively registered

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.

Phase I/II study of oral fluoropyrimidine S-1 plus oral Leucovorin as first-line treatment for metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4093-4093 ◽  
Author(s):  
T. Yoshino ◽  
W. Koizumi ◽  
K. Yamaguchi ◽  
Y. Miyata ◽  
T. Kato ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Oral Fluoropyrimidine ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Adequate Organ Function ◽  
Grade 3

4093 Background: The results of phase I portion of the treatment with the oral S-1 (a new oral fluoropyrimidine) plus oral leucovorin (LV) in patients (pts) with untreated metastatic colorectal cancer (mCRC) was reported at ESMO 2006. Dose limiting toxicities (DLTs) were grade 3 stomatitis/pharyngitis, nausea, diarrhea, ileus and exanthema. The recommended doses (RDs) for this phase II portion were determined to be S-1 40 mg/m2 and LV 25 mg/body orally given twice daily on days 1 to 14 of a 28-day cycle. The PK profiles of S-1 plus LV were similar to those of S-1 monotherapy and UFT plus LV, respectively. The main purpose of this phase II portion is to evaluate the efficacy and safety of S-1 plus LV at RD level in pts with untreated mCRC. Methods: Pts were eligible as follows; unresectable mCRC with no prior chemotherapy or receiving adjuvant chemotherapy completed at least 6 months before, histologically proven adenocarcinoma, PS(ECOG) 0–2, age 20 to 75, measurable lesions, adequate organ function and written informed consent. The pts received 40 mg/m2 of S-1 plus 25 mg/body of LV twice daily as RD in this phase II portion. The primary endpoint was the objective response rates (RRs), and secondary endpoints were time to progression (TTP) and toxicities. Results: Between Sep 2004 and Jun 2006, 56 pts of 65 enrolled pts received the treatment at RD level. The objective RRs were 55% (36 of 65) for all pts and 55% (31 of 56) for pts at RD. Disease control rates (DCRs) were 86% (56 of 65) for all pts and 86% (48 of 56) for pts at RD. Median TTP was 5.5 months for pts at RD, with a median follow-up of 5.5 months. The median survival time is under observation. During the 6 months from starting the treatment, the most common grade 3/4 toxicities at RD were as follows: diarrhea, 23%; stomatitis, 20%; anorexia, 18%; and neutropenia 13%. Conclusions: A combination of S-1 plus oral LV is an effective, well tolerated, and convenient regimen in pts with untreated mCRC, without the addition of either oxaliplatin or irinotecan. The updated results of the objective RRs, DCRs, TTP reviewed extramurally, and detailed safety profile will be presented at the meeting. This trial was supported by Taiho pharmaceutical co., Ltd., Tokyo, Japan. No significant financial relationships to disclose.

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.

Phase II study of S-1 plus leucovorin (a new 1-week treatment regimen followed by a 1-week rest period) in patients with untreated metastatic colorectal cancer in Japan and China.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 598-598 ◽  
Author(s):  
Tadamichi Denda ◽  
Jin Li ◽  
Ruihua Xu ◽  
Jianming Xu ◽  
Koji Ikejiri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Treatment Regimen ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Rest Period ◽  
Progression Free Survival ◽  
Grade 3 ◽  
Japan And China

598 Background: The previous phase II study of the oral S-1 plus oral Leucovorin (LV) (2 weeks’ treatment regimen followed by a 2 week rest period) for patients (pts) with untreated metastatic colorectal cancer (mCRC) have shown to be effective, but the grade 3 toxicities (diarrhea, stomatitis, and anorexia) were observed with relatively high frequency. In this phase II study, we tried to improve the administration schedule of S-1 plus LV regimens for well-tolerated toxicities and evaluated the efficacy. Methods: Pts were eligible as follows: histologically confirmed adenocarcinoma, age≥20, ECOG PS 0-1, no prior chemotherapy, at least one measurable lesion by RECIST ver1.0 criteria, adequate organ function, and written informed consent. S-1 (40-60 mg bid) and LV (25 mg bid) were orally administered for 1 week, followed by an 1 week rest period. Treatment was repeated until the onset of disease progression or unacceptable adverse events occurred. The primary endpoint was the response rate (RR), and the secondary endpoints were efficacy and safety. Results: From October 2008 to June 2009, 73 pts were enrolled in Japan and China. Of the eligible 71 pts, median age was 60 (range 27-84), Male/Female was 38/33, PS:0/1 was 39/32, and Japan/China was 32/39. RR as primary endpoint was 53.5% (95% CI, 41.3-65.5), and Disease Control Rate was 83.1%. With a median follow-up period of 26.4 months, the median Progression Free Survival was 6.5 months. Median Overall Survival was 24.3 months with the survival rate of 77.5 % at 1 year and 53.2 % at 2 years. The incidences of grade 3 adverse drug reactions were diarrhea 8.3 %, stomatitis 8.3%, anorexia 2.8%, neutropenia 9.7%, and there was no treatment-related death. Conclusions: The newly improved 1 week S-1 plus LV treatment regimen showed good efficacy and better tolerability than the 2 weeks’ treatment regimen. This therapy showed promising activity in pts with untreated mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs. This trial was supported by Taiho Pharmaceutical CO., LTD. ClinicalTrials.gov Identifier: NCT00891332 .

Retrospective cohort study on the safety and efficacy of panitumumab for patients with metastatic colorectal cancer: The HGCSG1002 study—Analysis of after cetuximab refractory.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 541-541
Author(s):  
Yoshimitsu Kobayashi ◽  
Hiraku Fukushima ◽  
Takahide Sasaki ◽  
Satoshi Yuki ◽  
Hiroyuki Okuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Daily Practice ◽  
Free Survival ◽  
Naive Group ◽  
Significant Difference ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Egfr Antibody

541 Background: In the previous studies, panitumumab (Pmab) has been demonstrated the efficacy for patients with metastatic colorectal cancer (mCRC) in all treatment lines. It is still controversial about the efficacy of Pmab for patients that had progressed on prior cetuximab (Cmab), though there had been a few reports (from Metges et al. and Wadlow et al.) regarding the efficacy of Pmab after Cmab refractory or intolerance. To evaluate the efficacy and safety of Pmab in patients with cetuximab-refractory mCRC, in comparison with anti-EGFR antibody naïve patients (Cmab-naïve) and Cmab-refractory or intolerance patients (prior-Cmab). Methods: Two hundred patients with mCRC treated by Pmab contained chemotherapy were retrospectively registered from 20 centers in Japan (HGCSG 1002 study). Of these, the patients that were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin, and were administered Pmab monotherapy were included in this analysis. Results: Of 93 patients (44 prior-Cmab and 49 Cmab-naïve) were evaluated. There were no significant differences in the baseline characteristics of the patients in each group. The incidence of Grade 3 or higher any skin toxicities were higher in the Cmab-naïve (26.5.%) than in the prior-Cmab (11.4%). The overall response rate (RR) was not significantly difference (prior-Cmab/ Cmab-naïve, 9.1%/ 10.2%), but the disease control rate (DCR) was slightly higher in Cmab-naïve group (38.6%/ 55.1%, p=0.15). Progression free survival (PFS) and overall survival (OS) were follows: prior-Cmab/ Cmab-naïve, 2.8m/ 3.1m, 6.8m / 9.5m. There was a significant difference between the two groups in OS curve (p=0.04). Conclusions: Pmab was safely administered to heavily pretreated mCRC patients in daily practice. Although there were no significant differences in RR, DCS and PFS between prior-Cmab and Cmab-naïve, but the median OS was longer for the Cmab-naïve group compared with the prior-Cmab group. Therapeutic efficacies of Pmab for prior-Cmab patients did not comparable to those for Cmab-naïve patients. We are now performing a phase II trial on the efficacy of Pmab for Cmab-refractory mCRC patients.

A phase II study on third-line chemotherapy combined bevacizumab with S-1 for metastatic colorectal cancer with mutated KRAS: SAVIOR study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 552-552
Author(s):  
Akinori Takagane ◽  
Yasuhiro Miyake ◽  
Kouji Kobayashi ◽  
Naoki Nagata ◽  
Atsushi Sato ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Dihydropyrimidine Dehydrogenase ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Antitumor Effects ◽  
Grade 3 ◽  
Line Chemotherapy

552 Background: Anti-Epidermal growth factor receptor (EGFR) antibody therapy is expected to be effective in treatment for metastatic colorectal cancer (mCRC) with wild-type KRAS, but for mCRC with mutated KRAS, no salvage treatment has been established. We performed a phase II clinical study on 3rd-line chemotherapy combined bevacizumab with S-1, an oral fluorinated pyrimidine preparation containing a dihydropyrimidine dehydrogenase inhibitor, and bevacizumab for mCRC resistant to oxaliplatin and irinotecan. Methods: Subjects were mCRC patients with mutated KRAS, who showed aggravation even after 2 regimens with oxaliplatin and irinotecan. S-1 (80-120 mg/body) was administered for 4 weeks and withdrawn for 2 weeks. The dose of S-1 was decided according to the subjects’ body surface area. Bevacizumab (5 mg/kg) was administered on Days 1, 15, and 29. This treatment was provided until progression. The primary endpoint was disease control rate (DCR), and secondary endpoints were response rate (RR), median progression free survival (mPFS), overall survival (OS), and adverse event (AE). Results: A total of 31 subjects mutated KRAS were enrolled between August 2009 and July 2011. An independent review committee evaluated antitumor effects in eligible 29 of the 31 subjects in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST). Two subjects in whom antitumor effects could not be evaluated were excluded. The DCR was 69% (95% confidence interval [CI], 49.2-84.7%), RR 0% (95% CI, 0-12.3%), mPFS 3.7 months (95% CI, 2.7-6.5 months), OS 9.0 months (95% CI, 7.5-12.0 months), and the median observation period 9.0 months. In 30 subjects for safety evaluation, the incidence of Grade 3 or greater adverse events was 50%. There was no treatment-related death. Major adverse events were anorexia (Grade 3 or greater, 20%), diarrhea (Grade 3, 10%), and decreased hemoglobin (Grade 3 or greater, 16.7%). Conclusions: The results suggest that 3rd-line chemotherapy combined bevacizumab with S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS. Clinical trial information: NCT00974389.

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