Phase II study of sunitinib as second-line treatment for advanced gastric cancer

Yung Jue Bang, Yoon Koo Kang, Won K. Kang, Narikazu Boku, Hyuncheol Chung, Jen Shi Chen, Toshihiko Doi, Yan Sun, Lin Shen, Shukui Qin, Wai Tong Ng, Jennifer M. Tursi, Maria J. Lechuga, Dongrui Ray Lu, Ana Ruiz-Garcia, Alberto Sobrero

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Abstract

Purpose: This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy. Experimental design. Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life. Results: Of 78 patients enrolled, most had gastric adenocarcinoma (93.6%) and metastatic disease (93.6%). All were evaluable for safety and efficacy. Two patients (2.6%) had partial responses and 25 patients (32.1%) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95% confidence interval [CI], 1.6-2.6 months) and median OS was 6.8 months (95% CI, 4.4-9.6 months). Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6% and 29.4% of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome. Conclusions: The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.

Original languageEnglish
Pages (from-to)1449-1458
Number of pages10
JournalInvestigational New Drugs
Volume29
Issue number6
DOIs
Publication statusPublished - 2011 Dec 1

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Stomach Neoplasms
Disease-Free Survival
Stomach
Adenocarcinoma
Therapeutics
Pharmacokinetics
Confidence Intervals
Safety
Esophagogastric Junction
Stomatitis
Survival
Anorexia
Combination Drug Therapy
Neutropenia
Protein-Tyrosine Kinases
Nausea
Multicenter Studies
Fatigue
sunitinib
Diarrhea

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Bang, Y. J., Kang, Y. K., Kang, W. K., Boku, N., Chung, H., Chen, J. S., ... Sobrero, A. (2011). Phase II study of sunitinib as second-line treatment for advanced gastric cancer. Investigational New Drugs, 29(6), 1449-1458. https://doi.org/10.1007/s10637-010-9438-y
Bang, Yung Jue ; Kang, Yoon Koo ; Kang, Won K. ; Boku, Narikazu ; Chung, Hyuncheol ; Chen, Jen Shi ; Doi, Toshihiko ; Sun, Yan ; Shen, Lin ; Qin, Shukui ; Ng, Wai Tong ; Tursi, Jennifer M. ; Lechuga, Maria J. ; Lu, Dongrui Ray ; Ruiz-Garcia, Ana ; Sobrero, Alberto. / Phase II study of sunitinib as second-line treatment for advanced gastric cancer. In: Investigational New Drugs. 2011 ; Vol. 29, No. 6. pp. 1449-1458.
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abstract = "Purpose: This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy. Experimental design. Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life. Results: Of 78 patients enrolled, most had gastric adenocarcinoma (93.6{\%}) and metastatic disease (93.6{\%}). All were evaluable for safety and efficacy. Two patients (2.6{\%}) had partial responses and 25 patients (32.1{\%}) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95{\%} confidence interval [CI], 1.6-2.6 months) and median OS was 6.8 months (95{\%} CI, 4.4-9.6 months). Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6{\%} and 29.4{\%} of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome. Conclusions: The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.",
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Bang, YJ, Kang, YK, Kang, WK, Boku, N, Chung, H, Chen, JS, Doi, T, Sun, Y, Shen, L, Qin, S, Ng, WT, Tursi, JM, Lechuga, MJ, Lu, DR, Ruiz-Garcia, A & Sobrero, A 2011, 'Phase II study of sunitinib as second-line treatment for advanced gastric cancer', Investigational New Drugs, vol. 29, no. 6, pp. 1449-1458. https://doi.org/10.1007/s10637-010-9438-y

Phase II study of sunitinib as second-line treatment for advanced gastric cancer. / Bang, Yung Jue; Kang, Yoon Koo; Kang, Won K.; Boku, Narikazu; Chung, Hyuncheol; Chen, Jen Shi; Doi, Toshihiko; Sun, Yan; Shen, Lin; Qin, Shukui; Ng, Wai Tong; Tursi, Jennifer M.; Lechuga, Maria J.; Lu, Dongrui Ray; Ruiz-Garcia, Ana; Sobrero, Alberto.

In: Investigational New Drugs, Vol. 29, No. 6, 01.12.2011, p. 1449-1458.

Research output: Contribution to journalArticle

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T1 - Phase II study of sunitinib as second-line treatment for advanced gastric cancer

AU - Bang, Yung Jue

AU - Kang, Yoon Koo

AU - Kang, Won K.

AU - Boku, Narikazu

AU - Chung, Hyuncheol

AU - Chen, Jen Shi

AU - Doi, Toshihiko

AU - Sun, Yan

AU - Shen, Lin

AU - Qin, Shukui

AU - Ng, Wai Tong

AU - Tursi, Jennifer M.

AU - Lechuga, Maria J.

AU - Lu, Dongrui Ray

AU - Ruiz-Garcia, Ana

AU - Sobrero, Alberto

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Purpose: This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy. Experimental design. Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life. Results: Of 78 patients enrolled, most had gastric adenocarcinoma (93.6%) and metastatic disease (93.6%). All were evaluable for safety and efficacy. Two patients (2.6%) had partial responses and 25 patients (32.1%) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95% confidence interval [CI], 1.6-2.6 months) and median OS was 6.8 months (95% CI, 4.4-9.6 months). Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6% and 29.4% of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome. Conclusions: The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.

AB - Purpose: This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy. Experimental design. Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life. Results: Of 78 patients enrolled, most had gastric adenocarcinoma (93.6%) and metastatic disease (93.6%). All were evaluable for safety and efficacy. Two patients (2.6%) had partial responses and 25 patients (32.1%) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95% confidence interval [CI], 1.6-2.6 months) and median OS was 6.8 months (95% CI, 4.4-9.6 months). Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6% and 29.4% of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome. Conclusions: The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.

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