Abstract LB-220: Translational research with RG7160 (GA201) leads to a phase II clinical study in combination with FOLFIRI in 2ndline metastatic colorectal cancer (mCRC)

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an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks.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.

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A phase II and co-clinical study of an AKT inhibitor in patients (pts) with biomarker-enriched, previously treated metastatic colorectal cancer (mCRC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.3563 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. 3563-3563 ◽

Cited By ~ 4

Author(s):

A. Dasari ◽

Michael J. Overman ◽

David R. Fogelman ◽

Bryan K. Kee ◽

David Menter ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Study ◽

Metastatic Colorectal Cancer ◽

Phase Ii ◽

Akt Inhibitor ◽

Previously Treated

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Phase II Trial of Cetuximab in Combination With Fluorouracil, Leucovorin, and Oxaliplatin in the First-Line Treatment of Metastatic Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.13.2183 ◽

2007 ◽

Vol 25 (33) ◽

pp. 5225-5232 ◽

Cited By ~ 233

Author(s):

Josep Tabernero ◽

Eric Van Cutsem ◽

Eduardo Díaz-Rubio ◽

Andrés Cervantes ◽

Yves Humblet ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Study ◽

Metastatic Colorectal Cancer ◽

Phase Ii ◽

Progression Free Survival ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Curative Intent ◽

First Line Treatment

PurposeThis phase II study investigated the efficacy and safety of cetuximab combined with standard oxaliplatin-based chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin [FOLFOX-4]) in the first-line treatment of epidermal growth factor receptor–expressing metastatic colorectal cancer (mCRC).Patients and MethodsThe activity of cetuximab plus oxaliplatin was investigated in colon cancer cell lines and xenograft models. In the clinical study, patients with mCRC received on day 1 of a 14 day cycle, cetuximab (initial dose 400 mg/m2during week 1, then 250 mg/m2weekly) followed by FOLFOX-4 (oxaliplatin 85 mg/m2on day 1; leucovorin 200 mg/m2on days 1 and 2, followed by fluorouracil 400 mg/m2bolus then 600 mg/m2intravenous infusion during 22 hours on days 1 and 2).ResultsThe preclinical studies confirmed the supra-additive activity of cetuximab to oxaliplatin. In the clinical study, 43 patients were included, with a median age of 65 years (range, 43 to 78 years). Response rates (RRs) were 79% (unconfirmed) and 72% (confirmed), with 95% disease control. Median progression-free survival (mPFS) and median duration of response were 12.3 and 10.8 months, respectively. Ten patients (23%) underwent resection with curative intent of previously unresectable metastases. After a median follow-up of 30.5 months, median overall survival (mOS) was 30.0 months. Cetuximab did not increase the characteristic toxicity of FOLFOX-4 and was generally well tolerated.ConclusionCetuximab in combination with FOLFOX-4 is a highly active first-line treatment for mCRC, showing encouraging RR, mPFS, and mOS values. The treatment resulted in a high resectability rate, which could potentially result in an improved cure rate. This combination is under phase III development.

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