Sequential methotrexate and 5-fluorouracil: improved response rate in metastatic colorectal cancer.

1984 ◽  
Vol 2 (6) ◽  
pp. 591-594 ◽  
Author(s):  
R Herrmann ◽  
J Spehn ◽  
J H Beyer ◽  
U von Franqué ◽  
A Schmieder ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Tumor Regression ◽  
Time Interval ◽  
Review Of The Literature ◽  
Human Colorectal Cancer ◽  
Multicenter Phase ◽  
Sequential Methotrexate

The efficacy of chemotherapy with sequential methotrexate (MTX) and 5-fluorouracil (5-FU) in metastatic colorectal cancer was studied in a multicenter phase II trial using a seven-hour time interval. Forty-two patients were evaluable for response and 16 achieved objective tumor regression (greater than 50%). Median survival of all patients was 12.5 months. The result of this study indicates that MTX and 5-FU are synergistic in human colorectal cancer if given sequentially with a seven-hour time interval. This is supported by a review of the literature that reveals a significantly higher response rate in patients treated with a four-hour or more MTX/5-FU interval as compared to a one-hour interval.

Safety report of a phase II trial of irinotecan plus S-1 (IRIS) with cetuximab in patients with KRAS wild type of metastatic colorectal cancer: HGCSG0902.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14062-e14062
Author(s):  
Yoshito Komatsu ◽  
Satoshi Yuki ◽  
Takashi Kato ◽  
Ayumu Hosokawa ◽  
Ichiro Iwanaga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Safety Analysis ◽  
Wild Type ◽  
Safety Report ◽  
Multicenter Phase ◽  
Secondary Endpoints ◽  
Grade 3

e14062 Background: IRIS is one of the standard regimens as second line treatment in metastatic colorectal cancer since IRIS demonstrated the non-inferiority to FOLFIRI (FIRIS study) in Japan. We previously presented IRIS plus bevacizumab (ESMO 2010), however; there is still lack of combination data of IRIS plus molecular target drugs. Thus we conduct the study of IRIS plus cetuximab (HGCSG0902) and this is the planned safety analysis for first 20 patients. Methods: HGSCG0902 is a multicenter phase ll study. Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS wild type. Patients (pts) received S-1 80-120 mg/m2/day p.o. on days 1-14 and irinotecan 100mg/m2 on days 1 and 15 repeated 28 days. Cetuximab administrated 400mg/m2 loading dose and continued 250mg/m2 every week or 500mg/m2 bi-weekly. The primary endpoint was response rate and the secondary endpoints were disease control rate, PFS, OS and safety. Results: Demographics of the 20 enrolled pts were male/female: 13/7, median age: 64.5, colon/rectal: 13/7, PS0/1: 12/8, prior bevacizumab +/-: 15/4 pts. Cetixumab were administrated weelkly/bi-weekly: 9/11 pts. 70% of pts had adverse events (AE). The most common non-hematological AE were diarrhea (85%), acne-like rash (80%), fatigue (75%) and anorexia (60%) and hematological AE were anemia (90%), AST increase (75%) and ALT increase (70%). The main grade 3-4 AE were diarrhea (45%), acne-like rash (20%), anorexia (20%) and stomatitis (20%). These AE were as expected. Nineteen pts stopped the treatment due to progression (52.6%) and AE (36.8%). Conclusions: This safety analysis suggests that IRIS plus cetuximab is well-tolerated and easy to administer.

Multicenter phase Ib/II study of everolimus (RAD001) and tivozanib (AV-951) in patients with refractory, metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
Brian M. Wolpin ◽  
Kimmie Ng ◽  
Andrew X. Zhu ◽  
Thomas Adam Abrams ◽  
Peter C. Enzinger ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Once Daily ◽  
Phase Ib ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Ecog Ps

560 Background: Everolimus (E) is an oral inhibitor of mTOR. Tivozanib (T) is a highly potent, selective, oral inhibitor of VEGF receptors-1, -2, and -3. Preclinical data suggest antitumor activity for this combination in colorectal cancer. We therefore performed a multicenter Phase Ib trial of E + T in patients (pts) with any refractory gastrointestinal (GI) malignancy, followed by a Phase II trial of E + T in pts with refractory, metastatic colorectal cancer (mCRC). Methods: Eligibility criteria: histologically confirmed, measurable disease; ECOG PS≤2; blood pressure ≤150/100; no venous thromboembolism within prior 6 months. Pts with mCRC must have received prior fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab and anti-EGFR antibody (if KRAS wt). E was administered once daily continuously. T was administered once daily for 3 out of every 4 weeks. The Phase Ib study in pts with any GI malignancy followed a standard 3+3 design with 3 dose levels: (1) E 5 mg/d + T 1 mg/d; (2) E 10 mg/d + T 1 mg/d; (3) E 10 mg/d + T 1.5 mg/d. The Phase II study in pts with mCRC was a non-randomized, one-stage design with a primary endpoint of progression-free survival. Results: Between 02/10-12/10, 12 pts were enrolled to the Phase Ib study. Median age, 60 (39-81) years; male, 50%; ECOG PS 0/1/2, 42/58/0%; tumor types: esophagus 1, colorectal 11 pts. Dose limiting toxicities of grade 3 fatigue and grade 3 fatigue/ dehydration occurred in 2/6 pts on dose level 3. Grade 3/4 treatment-related adverse events in ≥10% of pts were dehydration, fatigue, headache, hyperglycemia, hypertension, and hypophosphatemia. The phase II study proceeded at the maximally tolerated dose (MTD) of E 10 mg/d and T 1 mg/d. Between 02/11-06/11, 40 pts with mCRC were enrolled to the phase II study. All but 1 pt received prior bevacizumab. Median age, 56 (35-81) years; male, 48%; ECOG PS 0/1/2, 45/53/2%. Treatment is ongoing. Conclusions: Among pts with refractory GI malignancies, the combination of Everolimus + Tivozanib was well-tolerated with MTD of E 10 mg/d and T 1 mg/d. A phase II trial has completed enrollment using these doses of E + T in pts with refractory mCRC; safety and efficacy data will be available for presentation.

Cetuximab + capecitabine + irinotecan (CCI) versus cetuximab + capecitabine + oxaliplatin (CCO) as first line therapy for patients with metastatic colorectal cancer (CRC): Preliminary results of a randomized phase II trial of the AIO CRC Study Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3550-3550 ◽  
Author(s):  
V. Heinemann ◽  
L. Fischer Von Weikersthal ◽  
N. Moosmann ◽  
U. Vehling-Kaiser ◽  
M. Stauch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Karnofsky Performance Status ◽  
Objective Response ◽  
Standards Of Care ◽  
Preliminary Evaluation ◽  
Randomized Phase Ii

3550 Background: Combinations of infusional 5-FU/FA with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) have become standards of care in the treatment of metastatic colorectal cancer. In this trial, 5-FU/FA was replaced by capecitabine, an oral fluoropyrimidine. In addition, cetuximab, an antibody directed against the EGF-receptor was added to further improve treatment efficacy. Methods: Patients (pts) with metastatic CRC (age 18 to 75 years) and measurable disease were randomized to 3-week cycles of therapy. In the CCI-arm, pts received cetuximab (400 mg/m2 iv on day 1 of cycle 1 and 250 mg/m2 iv subsequently), capecitabine (2 × 800 mg/m2 po on days 1 to 14), and irinotecan (200 mg/m2 iv on day 1). In patients >65 years doses of irinotecan and capecitabine were reduced by 20%. In the CCO arm, cetuximab (as described above) was combined with capecitabine (2 × 1000 mg/m2 po on days 1 to 14) and oxaliplatin (130 mg/m2 iv on day 1). Both treatment arms were planned separately according to the optimal design described by Simon (p0 = 0.3, p1 = 0.5, α = 0.1, β = 0.1) with objective response rate (ORR) according to RECIST) as the primary endpoint. Results: The recruitment goal of 92 patients has been achieved. Among evaluable patients, median age in the CCI arm was 63 yrs (range 38–72) and 58 yrs (range 38–74) in the CCO arm. Median Karnofsky performance status was 90% (range 70–100) and 100% (range 70–100), the EGFR-status was positive in 64% and 69% of pts, respectively. The ORR in the CCI arm was 41% (11/27) (95%-CI: 22% to 61%), while in the CCO arm an ORR of 71% (15/21) (95%-CI: 48% to 89%) was documented. Toxicity data were available for 25 pts in each arm. The most common grade 3–4 CTC- toxicities observed in the CCI and the CCO-arm respectively were skin toxicity (4 vs 5 pts), allergic reactions (0 vs 5 pts), diarrhea (5 vs 3pts), neurotoxicity (1 vs 3 pts), and leucopenia (4 vs 5 pts). Conclusion: The preliminary evaluation of this randomized phase II trial suggests the feasibility of both treatment arms. Updated results regarding response rate and progression-free survival will be presented at the meeting. [Table: see text]

The efficacy and safety of irinotecan plus raltitrexed as second-line treatment in advanced colorectal cancer (ACC) patients: An interim analysis of a multicenter, phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15061-e15061
Author(s):  
Yunpeng Liu ◽  
Zan Teng ◽  
Xiujuan Qu ◽  
Yan qiao Zhang ◽  
Zhendong Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Multicenter Phase ◽  
Elevated Transaminases

e15061 Background: There are limited therapeutic options for the treatment of advanced colorectal cancer which fail first-line chemotherapy. Phase I studies have shown that the combined application of the irinotecan (CPT-11) and raltitrexed has significant synergistic effect and acceptable toxicity. The aim of this multicenter study was to assess the efficacy and toxicity of second-line raltitrexed plus irinotecan in Chinese patients with advanced colorectal cancer. Methods: This is an open-label,single-arm, multicenter, phase II trial (Registered in clinicaltrials.gov with NCT03053167).Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of oxaliplatin and fluorouracil therapy. Enrolled patients received CPT-11 (180 mg /m2 , d1) and raltitrexed (3 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were disease control rate (DCR), objective response rate (ORR), overall survival (OS), quality of life (QOL) and safety. In all, 100 patients were required for primary point testing. Results: Between November 2016 and December 2018, a total of 70 patients were screened for enrollment and 53 patients reached the primary endpoint. Nine patients achieved a partial response and twenty-seven stable disease. The overall response rate was 17% (9/53) and the disease control rate was 67.9% (36/53). Median progression-free survival (mPFS) was 4.3 months and median overall survival was not observed. The most common adverse events were elevated transaminases (21/53), fatigue (14/53), diarrhea (12/53), neutrocytopenia (10/53), erythrocytopenia (9/53), hypohemoglobin (8/53) and leukocytopenia (6/53). The total incidence of grade 3/4 toxicity was 17% (9/53) , mainly diarrhea (2/53), neutrocytopenia (2/53) and elevated transaminases (2/53). There were no treatment-related deaths. Conclusions: We have demonstrated that CPT-11 plus raltitrexed is active and feasible in patients with second-line treatment in advanced colorectal cancer. This trial will progress as planned. Clinical trial information: NCT03053167.

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