Phase II clinical study of combination therapy with irinotecan and S-1(IRIS) for inoperable recurrent advanced colorectal cancer: Hokkaido Gastrointestinal Cancer Study Group study HGCSG-0302)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3589-3589
Author(s):  
Y. Komatsu ◽  
S. Yuki ◽  
H. Akita ◽  
M. Kudo ◽  
M. Tateyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Study ◽  
Combination Therapy ◽  
Survival Time ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Dose Intensity ◽  
Outpatient Basis ◽  
Phase Ii Clinical Study

3589 Background: We planned to conduct a phase II clinical study of combination therapy with irinotecan and S-1, a new oral anticancer drug of the fluorinated pyrimidine type. We reported the interium reports of this study in colorectal cancer patients at GI cancer Symposium 2006. Methods: The antitumor effect was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20–75 years. Irinotecan was administered at a dose of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks. Results: Forty patients were enrolled in the present study. There were 23 men and 17 women. The median age was 62 years (range: 34 to 74 years). Two patient showed grade 4 neutropenia, but the next course could be given safely after dose reduction. Three patients had grade 3 diarrhea, but therapy could be continued with addition of an antidiarrheal drug. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Interim analysis suggested excellent results, with a response rate of 50%. To date, 231 cycles (median 8, range 1–19) have been administered. Median relative dose intensity was 97% for S-1 and 87% for irinotecan. 36 pts are evaluable for efficacy: RR was 47.2% (95% CI, 30.9–63.5%) and Disease Control Rate (PR + SD) was seen in 94.4% of pts. PFS of this regimen is 320 days. MST is not reached. Conclusions: IRIS therapy achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer. It seems that IRIS is a good treatment equal to FOLFIRI. In addition, this regimen could qualify as a candidate for future combination therapy with a molecular-targeting drug. The latest data will be reported at the meeting. No significant financial relationships to disclose.

Phase II clinical study of combination therapy with irinotecan and S-1(IRIS) for inoperable recurrent advanced colorectal cancer (2nd report): For Hokkaido Gastrointestinal Cancer Study Group (HGCSG)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4105-4105
Author(s):  
Y. Komatsu ◽  
S. Yuki ◽  
I. Iwanaga ◽  
M. Kudo ◽  
M. Tateyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Study ◽  
Combination Therapy ◽  
Survival Time ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
High Response Rate ◽  
Phase Iii ◽  
Outpatient Basis ◽  
Phase Ii Clinical Study

4105 Background: We planned to conduct a phase II clinical study of combination therapy with irinotecan and S-1, a new oral anticancer drug of the fluorinated pyrimidine type. We reported the interim reports of this study in colorectal cancer patients at ASCO 2006. Methods: The antitumor effect was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20–75 years. Irinotecan was administered at a dose of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks. Results: Forty patients were enrolled in the present study. There were 23 men and 17 women. The median age was 62 years (range: 34 to 74 years). Two patients showed grade 4 neutropenia, but the next course could be given safely after dose reduction. Three patients had grade 3 diarrhea, but therapy could be continued with addition of an antidiarrhea drug. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Forty pts. are evaluable for efficacy: RR was 52.5% (CR 1, PR 20, SD 17, PD 2, 95% CI, 37–68%) and Disease Control Rate (CR+PR+SD) was seen in 96.0% of pts. PFS of this regimen is 311 days. MST is not reached. Conclusions: IRIS therapy achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer. It seems that IRIS is a good treatment equal to FOLFIRI. Non-inferiority randomized phase III trial of IRIS vs. mFOLFOX6 (IFOX study) was planned, and it has been already started now. The latest data will be reported at the meeting. No significant financial relationships to disclose.

Randomized Multicenter Phase II Trial of Two Different Schedules of Capecitabine Plus Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer

2003 ◽  
Vol 21 (7) ◽  
pp. 1307-1312 ◽  
Author(s):  
Werner Scheithauer ◽  
Gabriela V. Kornek ◽  
Markus Raderer ◽  
Birgit Schüll ◽  
Katharina Schmid ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Synergistic Activity ◽  
Free Survival ◽  
Multicenter Phase ◽  
To Receive

Purpose: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study. Patients and Methods: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m2 day 1 plus capecitabine 2,000 mg/m2/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m2 days 1 and 14 combined with capecitabine 3,500 mg/m2 days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease. Results: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P = .0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%). Conclusion: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.

A randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase II clinical study of famitinib in the treatment of advanced metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 513-513 ◽  
Author(s):  
Rui-hua Xu ◽  
Lin Shen ◽  
Keming Wang ◽  
Gang Wu ◽  
Chunmei Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Study ◽  
Treatment Group ◽  
Adverse Events ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Control Group ◽  
Double Blind ◽  
Phase Ii Clinical Study ◽  
And Control

513 Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and is the fifth leading cause of cancer death in China. No standard care is available for patients with advanced CRC who failed the second-line treatment. Famitinib is a small-molecular, multi-target receptor tyrosine kinase inhibitor which primarily acts against angiogenesis. This phase II study was designed to evaluate the efficacy and safety of famitinib in the treatment of advanced colorectal cancer. Methods: This is a multi-center, randomized, double-blind, placebo-controlled, phase II clinical study (ClinicalTrials.gov Registration No.: NCT01762293). Totally 154 patients with advanced colorectal cancer who failed second or later-line treatments were randomized in a 2:1 ratio to receive either famitinib or placebo at 25 mg each day in each treatment cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and safety. The statistical analyses of endpoints were using intent-to-treat population. Results: Of 154 patients randomized, the mPFS was 2.8 and 1.5 months in the treatment group and control group, respectively (p=0.0034; HR=0.58). The ORR was 2.02% and 0.00% (p=0.54) and the DCR was 57.58% and 30.91% (p=0.0023) in the treatment group and control group, respectively. Analysis of OS data is ongoing. The frequently reported adverse events (AEs) include neutropenia, thrombocytopenia, hypertension, proteinuria, and hand-foot syndrome and were most grade 1/2. The incidences of serious adverse events (SAEs) for the famitinib and placebo groups were 11.11% and 9.09%, respectively (p=0.7884). Overall, famitinib was well tolerated and toxicities were manageable. Conclusions: Famitinib improved the PFS in patients with advanced metastatic colorectal cancer resulting in higher ORR and DCR in the treatment group with good safety and tolerability. Clinical trial information: NCT01762293.

Phase II study of oral S-1 monotherapy in metastatic colorectal cancer after failure of both irinotecan and oxaliplatin-containing regimen

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3597-3597
Author(s):  
B. Cho ◽  
H. Choi ◽  
H. Jeung ◽  
S. Rha ◽  
J. Ahn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
Skin Pigmentation ◽  
Dose Intensity ◽  
Line Therapy ◽  
Number Of Patients ◽  
Third Line

3597 Background: There has been a considerable increase in the number of patients (pts) with mCRC pretreated with both irinotecan and oxaliplatin. Little is known about third-line therapy in this group of pts. We conducted a phase II trial of oral S-1 in pts with advanced colorectal cancer who failed on both irinotecan and oxaliplatin. Methods: This phase II study was designed to evaluate the activity and toxicity of S-1 monotherapy in 31 advanced colorectal cancer pts (P0 = 3%, P1 = 15%; α = 0.05, power = 80%, drop-out rate 10 %). S-1 was administered orally twice daily, 70 mg/m2/day for 14 days followed by 1-week rest. Eligibility criteria included ECOG 0–2; measurable lesion; adequate organ functions; signed informed consent. Results: As of 1st September 2005, 21 pts were enrolled. Median age of all pts 55 years. There were 10 male and 11 females. Thirteen of 21 patients were treated with oxaliplatin-containing regimens as a first-line therapy for metastatic diseases. The median number of treatments was 3 courses (range, 1–10). The relative dose intensity was 1.0 (0.83 - 1.0) with a median dose of120 mg (100 -140 mg). Nineteen out of 21 patients were evaluable. The confirmed response rate was 21.1% (4/19, 1 CR, 3 PR). The median PFS was 11 weeks, and median OS was not reached. The most frequent adverse reaction was skin pigmentation (47.6%). Grade 3 toxicities was skin pigmentation in 1 patients (4.8%), neutropenia in 1 (4.8%), and anemia in 1 (4.8%), respectively. Conclusion: This results shows that S-1 produces a promising response rate with an acceptable safety profile in refractory, mCRC. S-1 has the potential to become a valuable option as a third-line salvage regimen in irinotecan and oxaliplatin pretreated mCRC pts. Clinical trial of combination therapy with S-1 will be warranted. No significant financial relationships to disclose.

Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study

2000 ◽  
Vol 18 (6) ◽  
pp. 1337-1345 ◽  
Author(s):  
Eric Van Cutsem ◽  
Michael Findlay ◽  
Bruno Osterwalder ◽  
Walter Kocha ◽  
David Dalley ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Dose Intensity ◽  
Patient Characteristics ◽  
Complete Response ◽  
Phase Iii ◽  
Effective Treatment Option ◽  
Randomized Phase Ii

PURPOSE: To evaluate in patients with advanced colorectal cancer (CRC) three treatment regimens of oral capecitabine in order to select the most appropriate regimen for testing in phase III. PATIENTS AND METHODS: Three capecitabine schedules were evaluated in a randomized phase II design: arm A, 1,331 mg/m2/d bid continuously; arm B, 2,510 mg/m2/d bid intermittently (2 weeks on/1 week off); and arm C, 1,657 mg/m2/d plus oral leucovorin 60 mg/d bid intermittently (2 weeks on/1 week off). RESULTS: One hundred nine patients were randomized; 39 patients were assessable for efficacy in arm A, 34 in arm B, and 35 in arm C. Patient characteristics were balanced in the arms. Confirmed tumor responses (partial response [PR] + complete response [CR]) were reported for eight patients with two CRs (21%; 95% confidence interval [CI], 9% to 36%) in arm A, eight patients with one CR (24%; 95% CI, 11% to 41%) in arm B, and eight patients with two CRs (23%; 95% CI, 10% to 40%) in arm C. Median times to progression (TTP) in arms A, B, and C were 127, 230, and 165 days, respectively. Overall, more toxicity was seen with capecitabine plus leucovorin, particularly diarrhea and hand-foot syndrome. There was no grade 3 or 4 marrow toxicity. CONCLUSION: Capecitabine offers a new, effective treatment option as an oral single agent in advanced CRC. Promising overall response rates were reported for all three regimens. The addition of leucovorin to the intermittent regimen had no marked effect on tumor response or median TTP. The intermittent single-agent capecitabine schedule is proposed for phase III evaluation, based on considerations of toxicity, dose-intensity, response rate, and TTP.

A phase II study of combination therapy with irinotecan and S-1 (IRIS) in patients with advanced colorectal cancer

2010 ◽  
Vol 66 (5) ◽  
pp. 987-992 ◽  
Author(s):  
Manabu Shiozawa ◽  
Makoto Akaike ◽  
Nobuhiro Sugano ◽  
Kazuhito Tsuchida ◽  
Naoto Yamamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Phase Ii Study

Phase II study of biweekly irinotecan and mitomycin C combination therapy in patients with fluoropyrimidine-resistant advanced colorectal cancer

2003 ◽  
Vol 52 (2) ◽  
pp. 125-130 ◽  
Author(s):  
Tadamichi Denda ◽  
Tomonori Ambo ◽  
Atsushi Ohtsu ◽  
Yasuhide Yamada ◽  
Kuniaki Shirao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Mitomycin C ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Phase Ii Study

Bi-weekly administration of capecitabine + oxaliplatin (Xelox-2) in first-line treatment of advanced colorectal cancer (ACRC): A phase II study of the Gruppo Oncologico dell’Italia Meridionale (GOIM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15066-e15066
Author(s):  
P. Fedele ◽  
G. Di Maggio ◽  
S. Leo ◽  
L. Nanni ◽  
F. Giuliani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
First Line ◽  
Main Site ◽  
First Line Therapy ◽  
Ecog Ps

e15066 Introduction: FOLFOX regimen represents a standard first-line therapy for ACRC pts. Oral capecitabine (XEL) has been shown to be a convenient and well tolerated alternative to intravenous 5-fluorouracil (5-FU) in the treatment of ACRC. Experimental data demonstrated the synergism of XEL with Oxaliplatin (OHP), but the questions about the most appropriate dosage and schedule of capecitabine have not yet been completely resolved. Taking into account these data the GOIM started a phase II study to evaluate the activity and the toxicity of biweekly administration of XEL plus OHP (XELOX-2) in ACRC pts. Methods: Previously untreated pts with histological diagnosis of metastatic colorectal cancer, measurable disease, ECOG PS<2, and age 18–75 yrs entered into this trial. The schedule of treatment was as follows: OHP at 100 mg/mq i.v. on days 1 and XEL at 2,000 mg/mq p.o. in two daily administrations from the 1 to the 7 day, every 2 weeks. RECIST and NCI criteria were employed to determine the activity and the toxicity of this regimen. Results: Fifty-one pts have been enrolled and up to now forty-seven are evaluable for activity and toxicity. The main characteristics of the entered pts were: sex (M/F) 38/13, median age 66,5 yrs (range 54–75 yrs), 28 (55%) single and 23 (45%) multiple site of disease. The main site of disease were liver in 38 pts (75%), lymph-nodes in 17 (33%), lung in 9 (18%). Two CR (4%) and 22 PR (47%), 13 SD (28%) and 10 PD (21%) were observed, with an overall response rate of 51% and a disease control rate (CR+PR+SD) of 79%. Median TTP was 5+ months (range 2–19). A total of 413 cycles were administered. In the evaluable pts the main toxicity rate (G1- 2 vs G3–4) were as follows: thrombocytopenia 51/6, anemia 42/0, neutropenia 15/0, nausea/vomiting 30/2, diarrhea 19/2, neurotoxicity 57/0 and asthenia 30/2. Only one pts presented G4 toxicity (diarrhea). Conclusions: These preliminary data show that the combination of XEL and OHP with a biweekly administration is active and well tolerated in ACRC pts. No significant financial relationships to disclose.

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