Cetuximab in Combination with Capecitabine and Cisplatin as First-Line Treatment in Advanced Gastric Cancer: Randomized Controlled Phase III Expand Study

4536 Background: To compare the efficacy and tolerance of two oxaliplatin-based regimens as first-line treatment of advanced gastric cancer. Methods: Chemotherapy-naïve patients with measurable recurrent or metastatic gastric adenocarcinoma, PS (ECOG) 0–2 and adequate organ functions were randomly assigned to receive either irinotecan 200mg/m2 and oxaliplatin 80mg/m2 (IO), every 21 days or oxaliplatin 85mg/m2 on day 1, 5-FU 400 mg/m2 (over 1 hour infusion) + 600mg/m2 (over 22 hours infusion) on days 1 and 2, leucovorin (LV) 200mg/m2 on days 1 and 2 (FOLFOX4) every 2 weeks. Study endpoints: Overall Response Rate (ORR), Toxicity Time to Progression (TTP) and Survival (S). Results: 138 patients were enrolled and all were evaluable for response. Median number of cycles administered was 5.5 (range 1–10) for IO and 7 (range 1–18) for FOLFOX4. In an intent-to treat analysis the ORR (RR+CR) was 29.4% for IO arm and 34.3 % for FOLFOX4 arm (p= 0.587). The median response duration was 5.63 months (mo) for IO arm and 6,6mo for FOLFOX4 arm. Median TTP was 4.2mo and 6,1mo for IO and FOLFOX4 arm respectively (p= 0.012). Median OS was 9.4mo for IO and 11.97mo for FOLFOX4 (p= 0.456). Toxicity was acceptable, with one toxic death in each arm. Grade 3–4 vomiting (7.3%), diarrhea (11.8%), neutropenia (22%) and febrile neutropenia (5.9%) occurred more frequently in IO arm, while anaemia (4.3%) and grade II neurotoxicity (11.4%) was more frequent in FOLFOX4 arm. Conclusions: Both regimens are well tolerated and active in advanced gastric cancer. Based on the TTP and toxicity profile, the FOLFOX4 regimen merits to be further evaluated in prospective phase III trials. No significant financial relationships to disclose.

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Cetuximab with irinotecan/folinic acid/5-FU as first-line treatment in advanced gastric cancer: A nonrandomized multicenter AIO phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4534 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4534-4534

Author(s):

S. Kanzler ◽

T. Trarbach ◽

T. Seufferlein ◽

S. Kubicka ◽

F. Lordick ◽

...

Keyword(s):

Gastric Cancer ◽

Folinic Acid ◽

Advanced Gastric Cancer ◽

Phase Ii ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Skin Reactions ◽

Oesophagogastric Junction ◽

First Line Treatment

4534 Background: Cetuximab has demonstrated high efficacy in combination with irinotecan-based therapies in metastatic colorectal cancer and irinotecan/folinic acid/5-FU (IF) may be an effective alternative to cisplatin-based regimens in advanced gastric cancer. We therefore conducted a phase II AIO study to evaluate the tolerability and efficacy of cetuximab combined with IF as first-line treatment in patients with advanced gastric cancer. Methods: Patients (pts) were eligible with untreated adenocarcinoma of the stomach or oesophagogastric junction, with ECOG performance status (PS) < 2, measurable lesions and adequate organ functions. Pts received weekly cetuximab (first dose 400 mg/m2, subsequent doses 250 mg/m2) combined with chemotherapy consisting of irinotecan (80 mg/m2) plus 24 hours continuous infusion of sodium folinic acid (Na-FA: 200 mg/m2) and 5-FU (1500 mg/m2) on days 1, 8, 15, 22, 29 and 36 of a 50-day cycle. Treatment was continued until tumor progression and tumor assessments were performed every 2nd cycle. Results: Between Aug 2006 and Sep 2007, 49 pts were enrolled: 71% were males, median age was 63 years (range 33–77), median PS was 0 (65% pts), and 69% of pts and 31% of pts had gastric and oesophagogastric junction carcinomas, respectively. The median treatment time was 15.2 weeks (range 1.1–69.1). Grade 3/4 toxicities were diarrhoea (17% pts), skin reactions (13% pts), anorexia (9% pts), anaemia and fatigue (7%pts), allergic reactions, leucopoenia and neutropenia (4% pts each). Among 48 response-evaluable pts, the overall response rate (CR + PR) was 42% (CR 4%/PR 38%) and the tumour control rate was 73%. Median progression-free and overall survival times were 8.5 months (36.6 weeks; 95% CI 30.1; 48.1) and 16.6 months (71.1 weeks; 95% CI 50; 93.4), respectively. Conclusions: Cetuximab plus IF was well tolerated and encouraging survival data were observed. Cetuximab combined with chemotherapy in advanced or metastatic gastric cancer is under further investigation in an ongoing phase III trial. No significant financial relationships to disclose.

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Randomized phase III study of S-1 plus oxaliplatin versus S-1 plus cisplatin for first-line treatment of advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.60 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 60-60 ◽

Cited By ~ 3

Author(s):

Katsuhiko Higuchi ◽

Wasaburo Koizumi ◽

Yasuhide Yamada ◽

Kazuhiro Nishikawa ◽

Masahiro Gotoh ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Phase Iii ◽

Outpatient Basis ◽

Line Treatment ◽

First Line ◽

Primary Analysis ◽

Serious Adverse Events ◽

Standard Regimen ◽

First Line Treatment

60 Background: S-1 plus cisplatin (SP) is the standard first-line treatment regimen for advanced gastric cancer (AGC) in Japan. S-1 plus oxaliplatin (SOX) for AGC showed promising efficacy and safety outcomes in the previous phase II study. We aimed to evaluate the non-inferiority of SOX to SP for AGC. Methods: Patients (Pts) with unresectable advanced or recurrent gastric cancer were randomly assigned to SOX (oral S-1 40 mg/m2 b.i.d. for 14 days plus oxaliplatin 100 mg/m2 iv on day 1, q3w) or SP (oral S-1 40 mg/m2 b.i.d. for 21 days plus cisplatin 60 mg/m2iv on day 8, q5w). Eligibility criteria included PS 0-2, age 20 years or older, adequate major organ functions. Primary endpoints were non-inferiority in progression-free survival (PFS) as compared with SP and relative efficacy in overall survival among the groups. Main secondary endpoints included response rate (RR), safety, and length of hospital stay (LOS) per cycle. The primary analysis for PFS was planned after 456 PFS events occurred. Results: Six hundred eighty five pts enrolled were randomly assigned to SOX (n=342) or SP (n=343) between Jan. 2010 and Oct. 2011. The evaluable pts for safety and efficacy were 673 (SOX/SP, 335/338) and 642 (SOX/SP, 318/324), respectively. The median PFS was 5.5 months for SOX vs. 5.4 months for SP (hazard ratio [HR] =1.004; 95% confidence interval [CI], 0.840-1.199). The upper limit of the 95% CI for HR was not above the margin of 1.30 and met the predefined criterion for non-inferiority. RR was 55.7% for SOX and 52.2% for SP (P=0.374). Grade 3 or 4 toxicities in SOX v. SP were neutropenia 19.5% v. 41.5%, thrombocytopenia 9.5% v. 10.4%, febrile neutropenia 0.9% v. 6.9%, hyponatremia 7.1% v. 15.2%, sensory neuropathy 4.4% v. 0%, respectively. Serious adverse events were occurred in 29.3 % for SOX and 37.9% for SP. Eight treatment-related deaths were reported in SP (2.4%) and four in SOX (1.2%). The median LOS per cycle was 0.85 day for SOX and 6.00 days for SP (P<0.0001). Conclusions: SOX showed non-inferiority to SP in PFS and the treatment was well tolerated, with benefit in terms of outpatient-based treatment in pts with AGC. SOX is considered as a new standard regimen for the first-line treatment of AGC on an outpatient basis. Clinical trial information: JapicCTI 101021.

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