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Multicenter Phase II study of FOLFOX or biweekly XELOX and Erbitux (cetuximab) as first-line therapy in patients with wild-type KRAS/BRAF metastatic colorectal cancer: The FLEET study.

Soda H, Maeda H, Hasegawa J, Takahashi T, Hazama S, Fukunaga M, Kono E, Kotaka M, Sakamoto J, Nagata N, Oba K, Mishima H - BMC Cancer (2015)

Bottom Line: The primary endpoint was response rate; secondary endpoints were progression-free survival, overall survival, disease control rate, dose intensity, conversion rate to surgical resection, and safety.The results of the present study indicate that biweekly cetuximab plus mFOLFOX-6/XELOX is an effective and tolerable treatment regimen.Registration date is 02/24/2010.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan. h-sodasoda@outlook.jp.

ABSTRACT

Background: The clinical benefit of cetuximab combined with oxaliplatin-based chemotherapy remains under debate. The aim of the present multicenter open-label Phase II study was to explore the efficacy and safety of biweekly administration of cetuximab and mFOLFOX-6 or XELOX as first-line chemotherapy in patients with metastatic colorectal cancer.

Methods: Sixty-two patients with previously untreated KRAS/BRAF wild-type metastatic colorectal cancer were recruited to the study between April 2010 and May 2011. Patients received one of two treatment regimens, either cetuximab plus mFOLFOX-6 (FOLFOX + Cmab) or cetuximab plus biweekly XELOX (XELOX + Cmab), according to their own preference. Treatment was continued until disease progression or the appearance of intolerable toxicities. The primary endpoint was response rate; secondary endpoints were progression-free survival, overall survival, disease control rate, dose intensity, conversion rate to surgical resection, and safety.

Results: The response rates in the FOLFOX + Cmab (n = 37) and XELOX + Cmab (n = 25) groups were 64.9 % (24/37) and 72.0 % (18/25), respectively. The median PFS in the FOLFOX + Cmab and XELOX + Cmab groups was 13.1 months (95 % confidence interval [CI] 12.1-17.5) and 13.4 months (95 % CI 10.1-17.9), respectively. Neutropenia was the most frequent grade 3/4 adverse event in both groups (33.9 %), followed by anorexia, acneiform eruption, skin fissure and paronychia. A waterfall plot of tumor diameter showed prominent shrinkage of the tumors in 88.7 % of patients.

Conclusions: The results of the present study indicate that biweekly cetuximab plus mFOLFOX-6/XELOX is an effective and tolerable treatment regimen. Biweekly administration of cetuximab requires only one hospital visit every 2 weeks, and may become a convenient treatment option for patients with KRAS/BRAF wild-type metastatic colorectal cancer.

Trial registration: This study is registered with University Hospital Medical Information Network (UMIN 000003253 ). Registration date is 02/24/2010.

No MeSH data available.


Related in: MedlinePlus

Maximum change in tumor size from baseline in individual patients over the course of treatment. Changes in tumor size (diameter) were assessed in patients treated with mFOLFOX-6 plus cetuximab (FOLFOX + Cmab) or XELOX plus cetuximab (XELOX + Cmab). Tumor shrinkage relative to baseline was observed in 88.7 % of patients, revealing the strength of combination therapy with cetuximab and oxaliplatin-based chemotherapy
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Fig3: Maximum change in tumor size from baseline in individual patients over the course of treatment. Changes in tumor size (diameter) were assessed in patients treated with mFOLFOX-6 plus cetuximab (FOLFOX + Cmab) or XELOX plus cetuximab (XELOX + Cmab). Tumor shrinkage relative to baseline was observed in 88.7 % of patients, revealing the strength of combination therapy with cetuximab and oxaliplatin-based chemotherapy

Mentions: Overall, two complete and 40 partial responses were observed (Table 2), and the RR for both groups was 67.7 %. Because 15 patients (24.2 %) had stable disease, the DCR was 91.9 %. There was no significant difference in the response rate between the FOLFOX + Cmab and XELOX + Cmab groups (64.9 % vs 72.0 %, respectively; P = 0.56, Chi-squared test). The median PFS in the FOLFOX + Cmab and XELOX + Cmab groups was 13.1 months (95 % confidence interval [CI] 11.4–18.3) and 13.4 months (95 % CI 10.1–17.9), respectively (Fig. 2). Furthermore, 88.7 % of patients exhibited prominent tumor shrinkage during treatment (Fig. 3). When response rate was assessed in patients with only one metastatic site, the response rates for liver, lung and lymph node metastases were 71.4 % (20/28), 75 % (3/4), and 57.1 % (4/7), respectively. At the final assessment, after a median follow-up of 36.3 months (95 % CI 28.4–35.6), 54.8 % of patients (34/62) had died: 88 % of the deaths were due to disease progression, and 6.5 % of patients (4/62) died of other causes, including pneumonia and unexpected accidents. The median OS in the FOLFOX + Cmab and XELOX + Cmab groups was 38.1 months (95 % CI 33.5–42.6) and 47.0 months (95 % CI 32.1–61.9), respectively.Table 2


Multicenter Phase II study of FOLFOX or biweekly XELOX and Erbitux (cetuximab) as first-line therapy in patients with wild-type KRAS/BRAF metastatic colorectal cancer: The FLEET study.

Soda H, Maeda H, Hasegawa J, Takahashi T, Hazama S, Fukunaga M, Kono E, Kotaka M, Sakamoto J, Nagata N, Oba K, Mishima H - BMC Cancer (2015)

Maximum change in tumor size from baseline in individual patients over the course of treatment. Changes in tumor size (diameter) were assessed in patients treated with mFOLFOX-6 plus cetuximab (FOLFOX + Cmab) or XELOX plus cetuximab (XELOX + Cmab). Tumor shrinkage relative to baseline was observed in 88.7 % of patients, revealing the strength of combination therapy with cetuximab and oxaliplatin-based chemotherapy
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4607014&req=5

Fig3: Maximum change in tumor size from baseline in individual patients over the course of treatment. Changes in tumor size (diameter) were assessed in patients treated with mFOLFOX-6 plus cetuximab (FOLFOX + Cmab) or XELOX plus cetuximab (XELOX + Cmab). Tumor shrinkage relative to baseline was observed in 88.7 % of patients, revealing the strength of combination therapy with cetuximab and oxaliplatin-based chemotherapy
Mentions: Overall, two complete and 40 partial responses were observed (Table 2), and the RR for both groups was 67.7 %. Because 15 patients (24.2 %) had stable disease, the DCR was 91.9 %. There was no significant difference in the response rate between the FOLFOX + Cmab and XELOX + Cmab groups (64.9 % vs 72.0 %, respectively; P = 0.56, Chi-squared test). The median PFS in the FOLFOX + Cmab and XELOX + Cmab groups was 13.1 months (95 % confidence interval [CI] 11.4–18.3) and 13.4 months (95 % CI 10.1–17.9), respectively (Fig. 2). Furthermore, 88.7 % of patients exhibited prominent tumor shrinkage during treatment (Fig. 3). When response rate was assessed in patients with only one metastatic site, the response rates for liver, lung and lymph node metastases were 71.4 % (20/28), 75 % (3/4), and 57.1 % (4/7), respectively. At the final assessment, after a median follow-up of 36.3 months (95 % CI 28.4–35.6), 54.8 % of patients (34/62) had died: 88 % of the deaths were due to disease progression, and 6.5 % of patients (4/62) died of other causes, including pneumonia and unexpected accidents. The median OS in the FOLFOX + Cmab and XELOX + Cmab groups was 38.1 months (95 % CI 33.5–42.6) and 47.0 months (95 % CI 32.1–61.9), respectively.Table 2

Bottom Line: The primary endpoint was response rate; secondary endpoints were progression-free survival, overall survival, disease control rate, dose intensity, conversion rate to surgical resection, and safety.The results of the present study indicate that biweekly cetuximab plus mFOLFOX-6/XELOX is an effective and tolerable treatment regimen.Registration date is 02/24/2010.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan. h-sodasoda@outlook.jp.

ABSTRACT

Background: The clinical benefit of cetuximab combined with oxaliplatin-based chemotherapy remains under debate. The aim of the present multicenter open-label Phase II study was to explore the efficacy and safety of biweekly administration of cetuximab and mFOLFOX-6 or XELOX as first-line chemotherapy in patients with metastatic colorectal cancer.

Methods: Sixty-two patients with previously untreated KRAS/BRAF wild-type metastatic colorectal cancer were recruited to the study between April 2010 and May 2011. Patients received one of two treatment regimens, either cetuximab plus mFOLFOX-6 (FOLFOX + Cmab) or cetuximab plus biweekly XELOX (XELOX + Cmab), according to their own preference. Treatment was continued until disease progression or the appearance of intolerable toxicities. The primary endpoint was response rate; secondary endpoints were progression-free survival, overall survival, disease control rate, dose intensity, conversion rate to surgical resection, and safety.

Results: The response rates in the FOLFOX + Cmab (n = 37) and XELOX + Cmab (n = 25) groups were 64.9 % (24/37) and 72.0 % (18/25), respectively. The median PFS in the FOLFOX + Cmab and XELOX + Cmab groups was 13.1 months (95 % confidence interval [CI] 12.1-17.5) and 13.4 months (95 % CI 10.1-17.9), respectively. Neutropenia was the most frequent grade 3/4 adverse event in both groups (33.9 %), followed by anorexia, acneiform eruption, skin fissure and paronychia. A waterfall plot of tumor diameter showed prominent shrinkage of the tumors in 88.7 % of patients.

Conclusions: The results of the present study indicate that biweekly cetuximab plus mFOLFOX-6/XELOX is an effective and tolerable treatment regimen. Biweekly administration of cetuximab requires only one hospital visit every 2 weeks, and may become a convenient treatment option for patients with KRAS/BRAF wild-type metastatic colorectal cancer.

Trial registration: This study is registered with University Hospital Medical Information Network (UMIN 000003253 ). Registration date is 02/24/2010.

No MeSH data available.


Related in: MedlinePlus