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Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF.

Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J - Br. J. Cancer (2005)

Bottom Line: Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously.Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper.The replacement of C by O and F by X does not appear to impair efficacy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Royal Marsden Hospital NHS Trust, Down's Road, Sutton, Surrey SM2 5PT, UK.

ABSTRACT
The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1% of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7% pts receiving F, 8.4% pts receiving X 500 mg m(-2) b.i.d.(-1) and 14.7% pts receiving X 625 mg m(-2) b.i.d.(-1). Combined complete and partial response rates were ECF 31% (95% CI 18.7-46.3), EOF 39% (95% CI 25.9-53.1), ECX 35% (95% CI 21.4-50.3), EOX 48% (95% CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7% of pts treated with X 625 mg m(-2) b.i.d.(-1), which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.

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Number of patients and fluoropyrimidine dose. Key: X(500)=capecitabine 500 mg m−2 b.i.d.−1. X(625)=capecitabine 625 mg m−2 b.i.d.−1.
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fig2: Number of patients and fluoropyrimidine dose. Key: X(500)=capecitabine 500 mg m−2 b.i.d.−1. X(625)=capecitabine 625 mg m−2 b.i.d.−1.

Mentions: In the first planned interim analysis, the first 80 pts were analysed for toxicity. Fluoropyrimidine-related toxicity (stomatitis, palmar-plantar erythema (PPE) and diarrhoea) was analysed according to fluoropyrimidine-containing regimen. The grade 3/4 fluoropyrimidine-related toxicity, in pts receiving X 500 mg m−2 b.i.d., was 5.1%; hence, the dose of X was escalated to 625 mg m−2 b.i.d. (Tebbutt et al, 2002). The trial protocol was amended to include this dose escalation and ethical approval was obtained by all the participating centres. The second interim analysis was performed when 204 pts had been recruited. Figure 2 illustrates the number of pts receiving each of the fluoropyrimidine doses: 103 pts received F 200 mg m−2 day−1, 60 pts X 500 mg m−2 b.i.d.−1 and 35 pts X 625 mg m−2 b.i.d.−1


Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF.

Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J - Br. J. Cancer (2005)

Number of patients and fluoropyrimidine dose. Key: X(500)=capecitabine 500 mg m−2 b.i.d.−1. X(625)=capecitabine 625 mg m−2 b.i.d.−1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361798&req=5

fig2: Number of patients and fluoropyrimidine dose. Key: X(500)=capecitabine 500 mg m−2 b.i.d.−1. X(625)=capecitabine 625 mg m−2 b.i.d.−1.
Mentions: In the first planned interim analysis, the first 80 pts were analysed for toxicity. Fluoropyrimidine-related toxicity (stomatitis, palmar-plantar erythema (PPE) and diarrhoea) was analysed according to fluoropyrimidine-containing regimen. The grade 3/4 fluoropyrimidine-related toxicity, in pts receiving X 500 mg m−2 b.i.d., was 5.1%; hence, the dose of X was escalated to 625 mg m−2 b.i.d. (Tebbutt et al, 2002). The trial protocol was amended to include this dose escalation and ethical approval was obtained by all the participating centres. The second interim analysis was performed when 204 pts had been recruited. Figure 2 illustrates the number of pts receiving each of the fluoropyrimidine doses: 103 pts received F 200 mg m−2 day−1, 60 pts X 500 mg m−2 b.i.d.−1 and 35 pts X 625 mg m−2 b.i.d.−1

Bottom Line: Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously.Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper.The replacement of C by O and F by X does not appear to impair efficacy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Royal Marsden Hospital NHS Trust, Down's Road, Sutton, Surrey SM2 5PT, UK.

ABSTRACT
The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1% of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7% pts receiving F, 8.4% pts receiving X 500 mg m(-2) b.i.d.(-1) and 14.7% pts receiving X 625 mg m(-2) b.i.d.(-1). Combined complete and partial response rates were ECF 31% (95% CI 18.7-46.3), EOF 39% (95% CI 25.9-53.1), ECX 35% (95% CI 21.4-50.3), EOX 48% (95% CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7% of pts treated with X 625 mg m(-2) b.i.d.(-1), which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.

Show MeSH
Related in: MedlinePlus