A randomized phase II study comparing oral S-1 plus 24-hour infusion of irinotecan (Iri) and bevacizumab (Bev) with FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer (MCRC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 613-613
Author(s):  
Sotaro Sadahiro ◽  
Toshiyuki Suzuki ◽  
Akira Tanaka ◽  
Kazutake Okada ◽  
Gota Saito ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
To Receive ◽  
First Line Treatment

613 Background: FOLFOX or FOLFIRI plus Bev is a first-line treatment for MCRC. Recent studies have confirmed that oral S-1 combined with Iri and Bev is equivalent to FOLFIRI plus Bev. Iri is usually administered as a short-term 90-min. infusion. However, the cytocidal activity is S-phase specific, and carboxylesterases, that convert Iri into SN-38, are less likely to become saturated when Iri is given as a long-term infusion. Therefore, a low dose of Iri given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare this regimen with FOLFIRI plus Bev. Methods: The subjects comprised 120 chemotherapy-naïve patients with MCRC. The study group received 24-hr infusion of Iri at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1 to 14. The FOLFIRI group received Iri at a dose of 150 mg/m2, 5-FU given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2400 mg/m2 as a 46 hr-infusion, 200 mg/m2 of leucovorin on days 1 and 15. Bev was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was the 1 y progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). Results: From October 2013 through December 2017, a total of 61 patients assigned to receive IRIS plus Bev (the A group) and 59 patients assigned to receive FOLFIRI plus Bev (the B group) were included in the analysis. The 1y RFS was 37.3% in the A group and 17.0% in the B group (p = 0.0281). The PFS was 10.2 mon in the A group and 10.0 mon in the B group, and the median OS was 27.0 mon and 28.6 mon, respectively (p = 0.26, p = 0.68). RR was significantly higher in the A group (87.0%) than in the B group (61.7%) (p = 0.005). The main grade 3 or 4 AEs were neutropenia (27.8%) and diarrhea (11.1%) in the A group and neutropenia (23.4%) and leukopenia (6.4%) in the B group. Conclusions: Our results showed that Iri, given biweekly as a 24-hour infusion in combination with oral S-1 and Bev, is a highly effective and well-tolerated regimen for the first-line treatment of MCRC. Clinical trial information: UMIN000014664.

Preliminary results from a phase II study of infusional 5-FU, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer (mCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3579-3579 ◽  
Author(s):  
S. Kopetz ◽  
J. L. Abbruzzese ◽  
C. Eng ◽  
R. B. Adinin ◽  
J. Morris ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Curative Surgery ◽  
Free Survival ◽  
Preliminary Results ◽  
Grade 3 ◽  
First Line Treatment

3579 Background: Irinotecan (I) plus bolus 5-FU (F) and leucovorin (L) comprise the IFL regimen, a very active treatment in mCRC when combined with bevacizumab (B). The response rate (RR) for IFL-B given as first-line treatment is 45%, with a median progression-free survival (PFS) of 10.6 months and a median survival of 20.3 months. The IFL regimen is now considered inferior to infusional 5-FU regimens, such as FOLFIRI, which have less toxicity and improved efficacy. Methods: We designed a 43 patient (pt), single-arm phase II trial of FOLFIRI-B with B (5mg/kg), I (180mg/m2), bolus of F (400mg/m2) and L (400mg/m2) followed by a 46-hour infusion of F (2400mg/m2), with a primary endpoint of progression-free survival (PFS). Chemotherapy naïve mCRC patients (pts) with adequate organ function and performance status 0–2 received B alone on Day minus 14, starting FOLFIRI + B on Day 1. DCE-MRI and laboratory correlates were completed before and after B alone and cycle 1. Once cycle is equivalent to two weeks. Results: 21 pts, median age 59 y/o (range 26–75), M:F = 15:6, 4 with prior F in adjuvant setting, have been enrolled to date. 20 pts are evaluable for response. One pt is too early. A total of 215 cycles have been administered (median 11). Median PFS has not been reached after a median follow-up of 8 months. By intent-to-treat analysis, there were 14 PRs (70%), and 5 (25%) pts with stable disease observed (including 1 unconfirmed PR). PRs were observed from 9 to 35 weeks after the first cycle (median: 18 weeks). 9 pts remain on treatment (1–12 months); 12 pts are off study (3 for progressive disease, 1 withdrew, 4 sent for curative surgery, 2 for toxicity, 2 sent for surgery unrelated to cancer). Toxicity included 10 cases of grade 3 neutropenia, including 1 febrile neutropenia, 4 venous thrombi, and 6 cases of hypertension requiring medication change. One pt included in the analysis developed peritonitis, considered a possible microperforation, after B alone and never received FOLFIRI. No ≥ grade 3 diarrhea was observed. Analysis of correlative studies will be presented at a later date. Conclusion: Our preliminary results indicate that FOLFIRI-B is well tolerated and an excellent choice as a first-line treatment for mCRC. [Table: see text]

Phase II study of bortezomib with cisplatin as first-line treatment of malignant pleural mesothelioma (MPM): EORTC 08052.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7081-7081 ◽  
Author(s):  
Mary O'Brien ◽  
Rabab Mohamed Gaafar ◽  
Sanjaykumar Popat ◽  
Francesco Grossi ◽  
Allan Price ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Dose Intensity ◽  
Line Treatment ◽  
First Line ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
First Line Treatment

7081 Background: Cisplatin is one of the most active drugs available in MPM while bortezomib has shown some activity in single agent phase II studies against MPM. This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of MPM. Methods: Patients with histological proven MPM, with performance status (PS) 0/1, were eligible. The doses were cisplatin 75mg/m2 /3 wks and bortezomib 1.3mg/m2 day 1, 4, 8, 11 every 3 wks. The primary end-point was progression free survival rate at 18 wks (PFSR=18). The 2-stage Simon design (a=0.1; b = 0.05, P0=0.50 and P1=0.675) was used. In the first step of the study 37 eligible patients were planned. If more than 19 patients were alive and free of progression at 18 wks the total sample size was increased to 76 eligible patients. Results: Between 2007 and 2010 82 patients were entered. The median follow-up time is 32.3 months The median age was 55 years (range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2: 42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The median number of cycles received was 4 and 38% received 6 cycles. Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4): neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4 hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus, grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3: 1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic progression) was 53% (80% confidence intervals, CI, 42-64%). The overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5). Conclusions: On the basis of the PFRS-18, the null hypothesis could not be rejected, although CB gave predictable toxicity and was as active as other reported regimens in MPM.

Phase II study of nimotuzumab combination with paclitaxel and cisplatin as the first-line treatment in patients with local advanced or metastatic esophageal squamous cell cancer (ESCC): An interim analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14604-e14604
Author(s):  
Xiaodong Zhang ◽  
Ming Lu ◽  
Jifang Gong ◽  
Jing Gao ◽  
Xicheng Wang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Treatment Plan ◽  
Cell Cancer ◽  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

e14604 Background: Nimotuzumab is a genetically engineered humanized antibody (mAb) that recognizes an epitope located in the extracellular domain of human EGFR. Evidences have shown that nimotuzumab is effective and safe in SCCHN. The combination of paclitaxel/cisplatin (TP) is a standard regimen for advanced or metastatic ESCC. This open uncontrolled phase II study was designed to determine the efficacy and safety of nimotuzumab in combination with TP as the first-line treatment in advanced ESCC. Methods: All patients have histology/cytology confirmed advanced or metastatic ESCC with ECOG PS 0-2. The treatment plan is as the following: paclitaxel administered intravenously (IV) 175 mg/m2 on d1 and cisplatin IV 30-35mg/ m2/d on d1-2, every 21 days for 6 cycles, and nimotuzumab IV 200mg weekly. For patients with stable disease (SD) and better, nimotuzumab will be given continuously after 6 cycles of TP. The primary endpoint is objective response rate (RR) with 56 patients enrollment (target RR >60%); secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety/ tolerability. The coordinations between EGFR and ERCC1 with response of treatment will be analyzed. Results: Up to date, 25 patients (male/female, 20/5; median age 58) have been enrolled. All patients were evaluated for toxicity and 22 are evaluable for response. 14 (63.6%) had a confirmed partial response (PR) and 7 (31.8%) had SD as their best responses with disease control rate of 95.4%. Only one patient had progressive disease (PD). Grade 3 or 4 neutropenia, neutropenic fever and anemia occurred in 52.2%, 4% and 13% respectively. Nonhematological toxicities were generally mild with grade 1 or 2 alopecie, hypodynamia, anorexia, nausea, arthralgia, and itch of skin occurring in 80%, 60.9%, 43.5%, 34.8%, 30.4%, and 21.7%. One patient had a grade 3 haematuria. Conclusions: The interim analysis showed that the combination of nimotuzumab with TP is tolerated reasonably well in patients with advanced or metastatic ESCC and encouraging efficacy. The study is ongoing with coordination of biomarkers and response as well.

Phase II study of weekly scheduled irinotecan and capecitabine treatment in advanced colorectal cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14644-e14644
Author(s):  
Wenhua Li ◽  
Jin Li ◽  
Jianming Xu ◽  
Lin Shen ◽  
Tianshu Liu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Current Phase ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Severe Diarrhea ◽  
Grade 3 ◽  
Line Setting

e14644 Background: The clinical application of combination therapy of irinotecan and capecitabine is at a standstill due to the consideration on severe diarrhea. The aim of the current phase II study was to explore the optimal administration mode of these two drugs, and evaluate the safety and efficacy of weekly-scheduled XELIRI regimen (wXELIRI) in mCRC pts. Methods: Pts with unresectable, histologically confirmed mCRC were enrolled to receive wXELIRI: irinotecan 90mg/m(2) on Day 1 and capecitabine 1200 mg/m(2) bid on Days 1-5 weekly. Both the first-line pts and second-line treatment pts who failed with FOLFOX or XELOX were eligible. The primary endpoint was rate of Grade 3/4 diarrhea. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and other safeties. Results: From January 2011 to May 2012, totally 43 pts with measurable mCRC were enrolled, 18 of them were male and 25 were female. The median age was 60 yrs (range 32-70). No Grade 4 diarrhea was observed and the rate of grade 3 diarrhea was 4.7%. The most common Grade 3/4 toxicities included leucocyte(11.6%), neutrophile (18.6%), vomiting (4.7%), fatigue (2.3%), hand-foot-syndrome (2.3%) . With a median follow-up of 19.0 months, 23 PFS events were observed. The mPFS for all the 43 pts was 6.1 mons and the mOS was 15.5 mons. For the 31 first-line treatment pts, the mPFS was 7.5 mons and the mOS has not reached. In the second-line treatment group (12 pts), the mPFS was 5.4 mons and mOS was 13.8 mons. Conclusions: The weekly-scheduled irinotecan and capecitabine combination has a low rate of severe diarrhea and acceptable toxicity profile. It could be an alternative regimen for mCRC pts, especially in the second-line setting. Clinical trial information: NCT01322152.

Pazopanib and 5-FU/oxaliplatin as first-line treatment in advanced gastric cancer: PaFLO, a randomized phase II study from the AIO (Arbeitsgemeinschaft Internistische Onkologie).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 4033-4033 ◽  
Author(s):  
Peter C. Thuss-Patience ◽  
Salah-Eddin Al-Batran ◽  
Jens T Siveke ◽  
Nils Homann ◽  
Peter Malfertheiner ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Line Treatment ◽  
First Line ◽  
Randomized Phase Ii ◽  
First Line Treatment
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