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
- Authors
- Lee, J[Lee, Jeeyun]; Shin, SJ[Shin, Sang Joon]; Chung, IJ[Chung, Ik Joo]; Kim, TW[Kim, Tae Won]; Chun, HG[Chun, Hoo-Geun]; Shin, DB[Shin, Dong Bok]; Kim, YH[Kim, Yeul Hong]; Song, HS[Song, Hong Suk]; Han, SW[Han, Sae-Won]; Kim, JG[Kim, Jong Gwang]; Kim, SY[Kim, Sun Young]; Choi, YJ[Choi, Young Jin]; Chung, HC[Chung, Hyun Cheol]
- Issue Date
- Jun-2014
- Keywords
- Chemotherapy; Colorectal cancer; TSU-68
- Citation
- INVESTIGATIONAL NEW DRUGS, v.32, no.3, pp.561 - 568
- Indexed
- SCIE
SCOPUS
- Journal Title
- INVESTIGATIONAL NEW DRUGS
- Volume
- 32
- Number
- 3
- Start Page
- 561
- End Page
- 568
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/52836
- DOI
- 10.1007/s10637-014-0075-8
- ISSN
- 0167-6997
- Abstract
- 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.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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