Progression-free survival in a phase II study of perioperative bevacizumab plus XELOX in patients with potentially curable metastatic colorectal cancer

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 4073-4073 ◽  
Author(s):  
T. Gruenberger ◽  
K. Kaczirek ◽  
M. Bergmann ◽  
C. C. Zielinski ◽  
B. Gruenberger
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Free Survival

Phase II Study of Capecitabine, Oxaliplatin, and Erlotinib in Previously Treated Patients With Metastastic Colorectal Cancer

2006 ◽  
Vol 24 (12) ◽  
pp. 1892-1897 ◽  
Author(s):  
Jeffrey A. Meyerhardt ◽  
Andrew X. Zhu ◽  
Peter C. Enzinger ◽  
David P. Ryan ◽  
Jeffrey W. Clark ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Early Stage ◽  
Progression Free Survival ◽  
Early Stage Disease ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

Purpose To investigate the combination of erlotinib, capecitabine, and oxaliplatin in patients who were previously treated for metastatic colorectal cancer. Patients and Methods Patients were eligible if they had metastatic colorectal cancer that progressed, were intolerant to first-line chemotherapy, or had disease recurrence within 1 year of adjuvant therapy for early-stage disease. Each 21-day cycle consisted of daily oral erlotinib at 150 mg, oral capecitabine at 1,000 mg/m2 (reduced to 750 mg/m2 after the first 13 patients) twice a day on days 1 to 14, and intravenous oxaliplatin at 130 mg/m2 on day 1. Results Thirty-two patients were enrolled onto this phase II study. By intention-to-treat analyses, eight patients (25%) experienced a partial response and 14 patients (44%) had stable disease for at least 12 weeks. The median progression-free survival was 5.4 months and the median overall survival was 14.7 months. These results were essentially unchanged when limited to the cohort of patients (78%) who received prior irinotecan for metastatic colorectal cancer. Most common grade 3 to 4 toxicities included diarrhea (38%), nausea/emesis (19%), fatigue (16%), dehydration (16%), and dermatitis (13%); grade 3 or 4 toxicities were reduced with a lower starting dose of capecitabine. Conclusion The combination of capecitabine, oxaliplatin, and erlotinib seems to have promising activity against metastatic colorectal cancer in patients who received prior chemotherapy, with a relatively higher response rate and progression-free survival compared with previous reports of either infusional FU, leucovorin, and oxaliplatin or capecitabine and oxaliplatin in similar patient populations.

scholarly journals Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironaga Satake ◽  
Koji Ando ◽  
Eiji Oki ◽  
Mototsugu Shimokawa ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.

scholarly journals Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer

2013 ◽  
Vol 7 ◽  
pp. CMO.S10769 ◽  
Author(s):  
◽  
Yutaka Ogata ◽  
Takaho Tanaka ◽  
Yoshito Akagi ◽  
Nobuya Ishibashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Overall Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Colorectal Cancer ◽  
Free Survival ◽  
Multicenter Phase ◽  
Grade 3

Introduction This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer. Patients and Methods Patients received first-line chemotherapy comprising S-1 80 mg/m2/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m2 CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle. Results A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%. Conclusions This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS.

Interim analysis of a single-arm, phase II study of bevacizumab (BV) with modified OPTIMOX1 as first-line treatment of patients with metastatic colorectal cancer (mCRC): TCOG-GI0802.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 578-578
Author(s):  
M. Asano ◽  
S. Tanaka ◽  
A. Sato ◽  
N. Nakayama ◽  
K. Shimada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii Study ◽  
Treatment Options ◽  
Optimal Schedule ◽  
Progression Free Survival ◽  
Chemotherapy Response ◽  
First Line ◽  
Free Survival ◽  
Modified Folfox6

578 Background: BV is widely used for treatment of metastatic colorectal cancer (mCRC) patients. Although BV was often administrated to mCRC patients in combination with oxaliplatin, optimal schedule remains unclear. Many mCRC patients cannot continue to use oxalipatin because of cumulative neurotoxity, which decreases patient's QOL and motivation.We postulated that modification of oxaliplatin schedule would improve TTF in intermittent oxaliplatin usage. Therefore, we planned to use BV with original OPTIMOX1 adiministration schedule; modified oxaliplatin dose (85 mg/m3). Methods: Patients were enrolled with the criteria excluding neuropathy, PS ≥ 1, or no previous usage of oxaliplatin and BV, and then were received modified FOLFOX6 regimen (L-OHP 85 mg/m2, l-LV 200 mg/m2, 5-FU 400 mg/m2 bolus, 5-FU 2,400 mg/m2 46h continuous infusion) plus BV (5 mg/kg) q2wks x 6 cycles, followed sLV5FU2 (omit L-OHP) plus BV x 12 cycles regimen. After that, oxaliplatin reintroduction was done and mFOLFOX6 plus BV regimen was continued until PD. The evaluation of antitumor effect was done according to RECIST Criteria. Results: 40 patients accrued this trial. Median age was 65 years old. PS0: 89.5%, male: 75%, female: 25%, colon: 65.8%, rectal: 31.6%,colon + rectal: 2.6%. During initial 6 cycles of chemotherapy, 90% patients could continue chemotherapy. Response rate was 50%, and clinical benefit (including SD) was 92.1%. During Intial 6 cycles, G3 neuropathy occurred 2.6%, and G2 were 5%. Most frequent toxicity (≥G3) was neutropenia (30.8%) and anorexia (5.3%). One patient could complete the scheduled regimen. This patient continued mFOLFOX6+BV for 12 cycles after reintroduction keeping with PS 0, and was received FOLFIRI+BV regimen as second-line chemotherapy. Further information are under examination. Conclusions: This administration schedule was well tolerated and could continue chemotherapy longer than usual method. sLV5FU2+BV regimen was not affected reintroduction rate and progression free survival. BV with mOPTIMOX1 regimen can be expected to become a good treatment options for mCRC patients. No significant financial relationships to disclose.

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 .

Multicenter Phase II Study of Bimonthly High-Dose Leucovorin, Fluorouracil Infusion, and Oxaliplatin for Metastatic Colorectal Cancer Resistant to the Same Leucovorin and Fluorouracil Regimen

1999 ◽  
Vol 17 (11) ◽  
pp. 3560-3568 ◽  
Author(s):  
Thierry André ◽  
Mohamed A. Bensmaine ◽  
Christophe Louvet ◽  
Eric François ◽  
Virginie Lucas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
High Dose ◽  
Median Response ◽  
Grade 3

PURPOSE: To evaluate the objective tumor response rates and toxicities of leucovorin (LV) plus fluorouracil (5-FU) cancer regimen combined with oxaliplatin (85 mg/m2) every 2 weeks on metastatic colorectal cancer patients with documented proof of progression while on bimonthly LV and 5-FU alone. PATIENTS AND METHODS: One hundred patients were enrolled onto this study and 97 received the study drugs between October 1995 and December 1996. Eighty-nine patients were eligible for per-protocol efficacy analysis with documented proof of progression on one of the following two treatments: LV 500 mg/m2 and continuous 5-FU infusion 1.5 to 2 g/m2/22 hours, days 1 through 2 every 2 weeks (FOLFUHD); or LV 200 mg/m2, bolus 5-FU 400 mg/m2, and continuous 5-FU infusion 600 mg/m2/22 hours, days 1 through 2 every 2 weeks (LV5FU2). In our study, 40 patients received FOLFUHD + 85 mg/m2 of oxaliplatin day 1 (FOLFOX3) and 57 patients received LV5FU2 + 85 mg/m2 of oxaliplatin day 1 (FOLFOX4). RESULTS: Of the 97 patients treated, 20 partial responses were observed (FOLFOX3/4: response rate, 20.6%; 95% confidence interval, 13% to 31.1%; FOLFOX3: response rate,18.4%; FOLFOX4: response rate, 23.5%). For patients treated with FOLFOX3/4, the median response duration for was 7.5 months, and the major toxicities were peripheral neuropathy and neutropenia. The incidence of grade 3 (National Cancer Institute common toxicity criteria) peripheral neuropathy was 20.6%; whereas the overall incidence of grade 3 to 4 neutropenia was 27.8%, 15%, and 36.9% for FOLFOX3/4, FOLFOX3, and FOLFOX4, respectively (P = .02). From the start of treatment, median progression-free survival was 4.7, 4.6, and 5.1 months for FOLFOX3/4, FOLFOX3, FOLFOX4, respectively, and median overall survival was 10.8, 10.6, and 11.1 months, respectively. CONCLUSION: This phase II study of oxaliplatin at 85 mg/m2 in combination with bimonthly LV plus 5-FU in patients with colorectal cancer resistant to LV plus 5-FU alone confirms the enhanced antitumor activity of oxaliplatin in combination with 5-FU.

Phase II study alternating mFOLFOX 6 and FOLFIRI (FIREFOX) plus bevacizumab (bev) regimen in first-line treatment of advanced colorectal cancer in Japanese patients (KSCC 0801).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 602-602
Author(s):  
Yutaka Ogata ◽  
Yoshito Akagi ◽  
Yoshihiro Kakeji ◽  
Yasunori Emi ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
First Line ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Ecog Ps

602 Background: The Kyushu Study group of Clinical Cancer conducted a phase II study that evaluated the FIREFOX regimen. (KSCC0701, Akagi et al, J Clin Oncol 28:15s, 2010). This study demonstrated the efficacy and mild neurotoxicity of this regimen. The present study evaluated the efficacy and safety of the FIREFOX plus bevacizumab (bev). Methods: Eligibility criteria included histologically confirmed advanced colorectal cancer, ECOG PS 0-2 and adequate bone marrow, renal and hepatic function. Patients (pts) received an alternating regimen of 4 cycles of mFOLFOX-6 plus bev (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bev 5 mg/kg d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) followed by 4 cycles of FOLFIRI plus bev (oxaliplatin replaced with irinotecan 150 mg/m2 d1). This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint is progression-free survival. (UMIN000001312) Results: Of the 52 pts enrolled from May 2008 to July 2009. Two of the patients did not fulfill the eligibility criteria. M/F, 30/20; median age, 59.5 years (range 37 - 75); ECOG PS 0/1/2, 46/4/0. The median number of administration cycles was 14 (range, 2 - 44). Response rate (RECIST criteria) for CR, PR, SD, PD and NE were 2 (4%), 28 (56%), 14 (28%), 4 (8%) and 2 (4%), respectively. An overall response rate was 60% (95% CI: 45 - 74%). Median progression-free survival was14.2 M (95% CI: 10.6 M-16.3 M) and median overall survival was 27.5 M (95% CI; 22.4 M – not determined). The 2-year survival rate was 56.8%. Of the 52 pts evaluated for toxicity. The most common grade 3-4 adverse events were leukopenia (7.7%), neutropenia (32.7%), anemia (1.9%), fatigue (9.6%), anorexia (13.5%), stomatitis (3.8%), neurotoxicity (3.8%), hypertension (1.9%), diarrhea (7.7%), febrile neutropenia (3.8%), nausea (9.6%), vomiting (5.8%), hypersensitivity (3.8%), and thromboembolism (1.9%). Conclusions: The results of this phase II study show that the FIREFOX plus bev regimen is effective and well tolerated in the first-line treatment of advanced colorectal cancer. The low rate of neurotoxicity is also promising.

A phase II study of lenvatinib in patients with metastatic colorectal cancer refractory to standard chemotherapy: LEMON study (NCCH1503).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3538-3538
Author(s):  
Hirokazu Shoji ◽  
Satoru Iwasa ◽  
Aya Kuchiba ◽  
Gakuto Ogawa ◽  
Mamiko Kawasaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Elevated Serum ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Correct Trial

3538 Background: Although regorafenib significantly improved overall survival compared with placebo for patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapies in the global phase III CORRECT trial, regorafenib is often discontinued due to toxicity. Lenvatinib is an inhibitor of VEGF receptors 1–3, FGF receptors 1–4, PDGF receptors α, RET, and KIT, showing receptor inhibition profile and kinetics different from regorafenib. This phase II study was conducted to evaluate the efficacy and safety of lenvatinib in patients with mCRC refractory to standard chemotherapies. Methods: mCRC patients with measurable lesions, PS 0-1, and refractory to standard chemotherapies including fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, cetuximab or panitumumab (if RAS wild-type), and TAS-102 (trifluridine/tipiracil) were eligible. Prior treatment with regorafenib was not allowed. Patients received lenvatinib orally at a dose of 24 mg once daily in 28-day cycles until unacceptable toxicity or disease progression. The primary endpoint was disease control rate (DCR) assessed by independent central review. Secondary endpoints included safety, response rate, progression-free survival (PFS), and overall survival. The planned sample size was 30 patients to expect a DCR of 60% with a threshold DCR of 35%, one-sided alpha of 5% and power of 80%. Results: Between October 2016 to January 2018, 30 patients were enrolled. All had received prior chemotherapy; 14 (47%) and 16 (53%) had received 3 or ≥ 4 prior lines for advanced disease, respectively. The median number of lenvatinib cycles was 4 (range 1-13). Two patients achieved partial response and 19 patients had stable disease, resulting in a response rate of 6.7% and DCR of 70.0% (95% CI: 50.6-85.3%). Median PFS was 3.6 months (95% CI: 2.6-3.7). The most common grade ≥ 3 adverse events were hypertension (53%), elevated serum aspartate aminotransferase (13%), thrombocytopenia (10%), and anorexia (7%) without unexpected safety signals. Conclusions: Lenvatinib showed promising antitumor activity with acceptable toxicity for patients with mCRC refractory to standard chemotherapies. Clinical trial information: UMIN000023446.

scholarly journals Phase II Study of Biweekly Pemetrexed Plus Irinotecan as Second-Line Therapy for Metastatic Colorectal Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
C. Louvet ◽  
T. André ◽  
E. Gamelin ◽  
M. Hebbar ◽  
M. Mabro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Vitamin Supplementation ◽  
Open Label ◽  
Common Grade ◽  
Duration Of Response ◽  
Grade 3

Background. This open-label, single-arm, two-stage, Phase II study investigated the efficacy and safety of bi-weekly pemetrexed combined with irinotecan, in patients with metastatic colorectal cancer (mCRC), after first-line chemotherapy using FOLFOX regimen.Patients and methods. Patients received pemetrexed 400 mg/m²as a 10-minute intravenous infusion (with vitamin supplementation) followed by irinotecan 180 mg/m²as a 90-minute infusion on day 1 of a 14-day cycle, for a maximum of 12 cycles. The primary endpoint was response rate (RR;H0≤5%,Ha≥20%,α=0.05, power = 90%). Secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and toxicities.Results. Partial response was observed in six out of 44 patients enrolled in the study (RR = 13.6%). The median PFS and OS were 4.0 and 13.9 months, respectively. The most common grade 3-4 toxicities were fatigue: 20.5% of patients, neutropenia: 18.6%, diarrhea: 13.6%, elevated transaminases: 9.5%, anemia: 9.3%, and vomiting: 6.8%.Conclusion. Pemetrexed plus irinotecan administered every two weeks is an active and well-tolerated regimen in mCRC patients pretreated with FOLFOX regimen. However, this regimen does not seem to provide clinically relevant advantage over historical data of a classical FOLFIRI regimen.

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