Multicenter phase II study of combination therapy with cetuximab and S-1 in patients with KRAS exon 2 wild-type unresectable colorectal cancer previously treated with irinotecan, oxaliplatin, and fluoropyrimidines (KSCC 0901 study)

Takao Takahashi, Yasunori Emi, Eiji Oki, Kazuma Kobayashi, Akihito Tsuji, Mototsugu Shimokawa, Takaho Tanaka, Yoshito Akagi, Yutaka Ogata, Hideo Baba, Kazuhiro Yoshida, Shoji Natsugoe, Yoshihiko Maehara, Study Group of Clinical Cancer (KSCC) Kyushu Study Group of Clinical Cancer (KSCC)

Research output: Contribution to journalArticle

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Abstract

Purpose: Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we examined the efficacy and safety of the combination of cetuximab and S-1 in patients with KRAS wild-type unresectable metastatic colorectal cancer who were previously treated with irinotecan, oxaliplatin, and fluoropyrimidines. Methods: The study was designed as a phase II, non-randomized, open-label, multicenter trial. Cetuximab was initially administered at 400 mg/m2, followed by weekly infusion at 250 mg/m2. S-1 was administered at a fixed dose of 80 mg/m2 orally twice daily for 28 days followed by a 14-day break, resulting in a 6-week treatment course. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), disease control rate (DCR), time to treatment failure, dose intensity, safety, and BRAF mutation status. Results: Thirty-seven patients were eligible. The median PFS was 5.5 months, the median OS was 13.5 months, the ORR was 29.7 %, and the DCR was 73.0 %. The relative dose intensity was 86.8 % for cetuximab and 88.1 % for S-1. Grade 3–4 adverse events that occurred in >10 % of the patient population included rash, dry skin, diarrhea, paronychia, anorexia, fatigue, mucositis, and neutropenia. Conclusions: Combination therapy with cetuximab and S-1 was effective and well tolerated in patients with irinotecan-, oxaliplatin-, and fluoropyrimidine-refractory metastatic colorectal cancer.

Original languageEnglish
Pages (from-to)585-593
Number of pages9
JournalCancer chemotherapy and pharmacology
Volume78
Issue number3
DOIs
Publication statusPublished - Sep 1 2016

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irinotecan
oxaliplatin
Colorectal Neoplasms
Exons
Disease control
Disease-Free Survival
Paronychia
Therapeutics
Safety
Mucositis
Epidermal Growth Factor Receptor
Refractory materials
Labels
Anorexia
Skin
Exanthema
Neutropenia
Treatment Failure
Multicenter Studies
Fatigue of materials

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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Multicenter phase II study of combination therapy with cetuximab and S-1 in patients with KRAS exon 2 wild-type unresectable colorectal cancer previously treated with irinotecan, oxaliplatin, and fluoropyrimidines (KSCC 0901 study). / Takahashi, Takao; Emi, Yasunori; Oki, Eiji; Kobayashi, Kazuma; Tsuji, Akihito; Shimokawa, Mototsugu; Tanaka, Takaho; Akagi, Yoshito; Ogata, Yutaka; Baba, Hideo; Yoshida, Kazuhiro; Natsugoe, Shoji; Maehara, Yoshihiko; Kyushu Study Group of Clinical Cancer (KSCC), Study Group of Clinical Cancer (KSCC).

In: Cancer chemotherapy and pharmacology, Vol. 78, No. 3, 01.09.2016, p. 585-593.

Research output: Contribution to journalArticle

Takahashi, T, Emi, Y, Oki, E, Kobayashi, K, Tsuji, A, Shimokawa, M, Tanaka, T, Akagi, Y, Ogata, Y, Baba, H, Yoshida, K, Natsugoe, S, Maehara, Y & Kyushu Study Group of Clinical Cancer (KSCC), SGOCCKSCC 2016, 'Multicenter phase II study of combination therapy with cetuximab and S-1 in patients with KRAS exon 2 wild-type unresectable colorectal cancer previously treated with irinotecan, oxaliplatin, and fluoropyrimidines (KSCC 0901 study)', Cancer chemotherapy and pharmacology, vol. 78, no. 3, pp. 585-593. https://doi.org/10.1007/s00280-016-3109-4
Takahashi, Takao ; Emi, Yasunori ; Oki, Eiji ; Kobayashi, Kazuma ; Tsuji, Akihito ; Shimokawa, Mototsugu ; Tanaka, Takaho ; Akagi, Yoshito ; Ogata, Yutaka ; Baba, Hideo ; Yoshida, Kazuhiro ; Natsugoe, Shoji ; Maehara, Yoshihiko ; Kyushu Study Group of Clinical Cancer (KSCC), Study Group of Clinical Cancer (KSCC). / Multicenter phase II study of combination therapy with cetuximab and S-1 in patients with KRAS exon 2 wild-type unresectable colorectal cancer previously treated with irinotecan, oxaliplatin, and fluoropyrimidines (KSCC 0901 study). In: Cancer chemotherapy and pharmacology. 2016 ; Vol. 78, No. 3. pp. 585-593.
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abstract = "Purpose: Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we examined the efficacy and safety of the combination of cetuximab and S-1 in patients with KRAS wild-type unresectable metastatic colorectal cancer who were previously treated with irinotecan, oxaliplatin, and fluoropyrimidines. Methods: The study was designed as a phase II, non-randomized, open-label, multicenter trial. Cetuximab was initially administered at 400 mg/m2, followed by weekly infusion at 250 mg/m2. S-1 was administered at a fixed dose of 80 mg/m2 orally twice daily for 28 days followed by a 14-day break, resulting in a 6-week treatment course. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), disease control rate (DCR), time to treatment failure, dose intensity, safety, and BRAF mutation status. Results: Thirty-seven patients were eligible. The median PFS was 5.5 months, the median OS was 13.5 months, the ORR was 29.7 {\%}, and the DCR was 73.0 {\%}. The relative dose intensity was 86.8 {\%} for cetuximab and 88.1 {\%} for S-1. Grade 3–4 adverse events that occurred in >10 {\%} of the patient population included rash, dry skin, diarrhea, paronychia, anorexia, fatigue, mucositis, and neutropenia. Conclusions: Combination therapy with cetuximab and S-1 was effective and well tolerated in patients with irinotecan-, oxaliplatin-, and fluoropyrimidine-refractory metastatic colorectal cancer.",
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T1 - Multicenter phase II study of combination therapy with cetuximab and S-1 in patients with KRAS exon 2 wild-type unresectable colorectal cancer previously treated with irinotecan, oxaliplatin, and fluoropyrimidines (KSCC 0901 study)

AU - Takahashi, Takao

AU - Emi, Yasunori

AU - Oki, Eiji

AU - Kobayashi, Kazuma

AU - Tsuji, Akihito

AU - Shimokawa, Mototsugu

AU - Tanaka, Takaho

AU - Akagi, Yoshito

AU - Ogata, Yutaka

AU - Baba, Hideo

AU - Yoshida, Kazuhiro

AU - Natsugoe, Shoji

AU - Maehara, Yoshihiko

AU - Kyushu Study Group of Clinical Cancer (KSCC), Study Group of Clinical Cancer (KSCC)

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Purpose: Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we examined the efficacy and safety of the combination of cetuximab and S-1 in patients with KRAS wild-type unresectable metastatic colorectal cancer who were previously treated with irinotecan, oxaliplatin, and fluoropyrimidines. Methods: The study was designed as a phase II, non-randomized, open-label, multicenter trial. Cetuximab was initially administered at 400 mg/m2, followed by weekly infusion at 250 mg/m2. S-1 was administered at a fixed dose of 80 mg/m2 orally twice daily for 28 days followed by a 14-day break, resulting in a 6-week treatment course. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), disease control rate (DCR), time to treatment failure, dose intensity, safety, and BRAF mutation status. Results: Thirty-seven patients were eligible. The median PFS was 5.5 months, the median OS was 13.5 months, the ORR was 29.7 %, and the DCR was 73.0 %. The relative dose intensity was 86.8 % for cetuximab and 88.1 % for S-1. Grade 3–4 adverse events that occurred in >10 % of the patient population included rash, dry skin, diarrhea, paronychia, anorexia, fatigue, mucositis, and neutropenia. Conclusions: Combination therapy with cetuximab and S-1 was effective and well tolerated in patients with irinotecan-, oxaliplatin-, and fluoropyrimidine-refractory metastatic colorectal cancer.

AB - Purpose: Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we examined the efficacy and safety of the combination of cetuximab and S-1 in patients with KRAS wild-type unresectable metastatic colorectal cancer who were previously treated with irinotecan, oxaliplatin, and fluoropyrimidines. Methods: The study was designed as a phase II, non-randomized, open-label, multicenter trial. Cetuximab was initially administered at 400 mg/m2, followed by weekly infusion at 250 mg/m2. S-1 was administered at a fixed dose of 80 mg/m2 orally twice daily for 28 days followed by a 14-day break, resulting in a 6-week treatment course. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), disease control rate (DCR), time to treatment failure, dose intensity, safety, and BRAF mutation status. Results: Thirty-seven patients were eligible. The median PFS was 5.5 months, the median OS was 13.5 months, the ORR was 29.7 %, and the DCR was 73.0 %. The relative dose intensity was 86.8 % for cetuximab and 88.1 % for S-1. Grade 3–4 adverse events that occurred in >10 % of the patient population included rash, dry skin, diarrhea, paronychia, anorexia, fatigue, mucositis, and neutropenia. Conclusions: Combination therapy with cetuximab and S-1 was effective and well tolerated in patients with irinotecan-, oxaliplatin-, and fluoropyrimidine-refractory metastatic colorectal cancer.

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