A phase II open-label randomized multicenter trial of TSU-68 in combination with S-1 and oxaliplatin versus S-1 in combination with oxaliplatin in patients with metastatic colorectal cancer

被引：5

作者：

Lee, Jeeyun ^{[1
]}

Shin, Sang Joon ^{[2
]}

Chung, Ik Joo ^{[3
]}

Kim, Tae Won ^{[4
]}

Chun, Hoo-Geun ^{[5
]}

Shin, Dong Bok ^{[6
]}

Kim, Yeul Hong ^{[7
]}

Song, Hong Suk ^{[8
]}

Han, Sae-Won ^{[9
]}

Kim, Jong Gwang ^{[10
]}

Kim, Sun Young ^{[11
]}

Choi, Young Jin ^{[12
]}

Chung, Hyun Cheol ^{[2
,13
]}

机构：

[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul, South Korea

[2] Yonsei Univ, Coll Med, Severance Hosp, Div Hematol Oncol,Dept Med, Seoul, South Korea

[3] Chonnam Natl Univ, Hwasun Hosp, Dept Med, Div Hematol Oncol, Kwangju, South Korea

[4] Asan Med Ctr, Div Hematol Oncol, Dept Med, Seoul, South Korea

[5] Seoul St Marys Hosp, Div Hematol Oncol, Dept Med, Seoul, South Korea

[6] Gachon Univ, Gil Hosp, Dept Med, Div Hematol Oncol, Inchon, South Korea

[7] Korea Univ, Anam Hosp, Dept Med, Div Hematol Oncol, Seoul, South Korea

[8] Keimyung Univ, Dongsan Hosp, Dept Med, Div Hematol Oncol, Seoul, South Korea

[9] Seoul Natl Univ Hosp, Dept Med, Div Hematol Oncol, Seoul 110744, South Korea

[10] Kyungpook Natl Univ Hosp, Div Hematol Oncol, Dept Med, Taegu, South Korea

[11] Natl Canc Ctr, Div Hematol Oncol, Dept Med, Goyang Si, South Korea

[12] Pusan Natl Univ Hosp, Div Hematol Oncol, Dept Med, Pusan, South Korea

[13] Yonsei Univ, Severance Hosp, Dept Med Oncol, Seoul 120752, South Korea

来源：

INVESTIGATIONAL NEW DRUGS | 2014年 / 32卷 / 03期

关键词：

Colorectal cancer; Chemotherapy; TSU-68; 1ST-LINE TREATMENT; PLUS IRINOTECAN; ORAL S-1; BEVACIZUMAB; FLUOROURACIL; LEUCOVORIN; EFFICACY; THERAPY; FOLFIRI; MARKERS;

D O I：

10.1007/s10637-014-0075-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. The combination of oxaliplatin-based treatments (oxaliplatin plus infusional 5-fluorouracil and leucovorin [FOLFOX] or oxaliplatin plus capecitabine [CapeOX]) and bevacizumab is a standard chemotherapy regimen for metastatic CRC (mCRC). However, several clinical studies that tested S-1 plus oxaliplatin (SOX) indicate that SOX is also a treatment option for mCRC. TSU-68 is an oral compound that inhibits vascular endothelial growth factor receptor and platelet-derived growth factor receptor. The recommended dose of TSU-68 + SOX was previously determined in a phase I study of mCRC patients. The goal of this trial was to evaluate the efficacy of TSU-68 in combination with SOX. Methods This open-label multicenter randomized phase II trial was performed in Korea. Treatment-naive mCRC patients with a performance status of 0 or 1 were randomized in a 1:1 ratio to receive either TSU-68 + SOX or SOX alone. The primary endpoint was progression-free survival (PFS). Results A total of 105 patients (TSU-68 + SOX, 52 patients; SOX alone, 53 patients) were randomized. The median PFS was 7.0 months in the TSU-68 + SOX group (hazard ratio [HR], 1.057) and 7.2 months in the SOX group (p = 0.8401). The most frequent grade 3 and 4 adverse events were thrombocytopenia (9.6 % [TSU-68 + SOX] vs. 26.4 % [SOX]), neutropenia (13.5 % [TSU-68 + SOX] vs. 15.1 % [SOX]), and anemia (3.8 % [TSU-68 + SOX] vs. 13.2 % [SOX]). We observed a difference between the 2 groups for all grades of anemia (15.4 % [TSU-68 + SOX] vs. 32.1 % [SOX]), diarrhea (30.8 % [TSU-68 + SOX] vs. 47.2 % [SOX]), vomiting (50.0 % [TSU-68 + SOX] vs. 26.4 % [SOX]), and chromaturia (23.1 % [TSU-68 + SOX] vs. 0.0 % [SOX]). Analysis using a Cox proportional hazard model showed that baseline interleukin 6 (IL-6) levels were associated with a survival benefit of TSU-68 (p = 0.012). Conclusion TSU-68 + SOX had a favorable safety profile. However, TSU-68 did not have a synergistic effect on the efficacy of SOX. The baseline serum IL-6 level could be a prognostic factor for TSU-68 efficacy.

引用

页码：561 / 568

页数：8

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