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.

Lee, Jeeyun; Shin, Sang Joon; Chung, Ik Joo; Kim, Tae Won; Chun, Hoo-Geun; Shin, Dong Bok; Kim, Yeul Hong; Song, Hong Suk; Han, Sae-Won; Kim, Jong Gwang; Kim, Sun Young; Choi, Young Jin; Chung, Hyun Cheol
Investigational new drugs
2014Jun ; 32 ( 3 ) :561-8.
저자 상세정보
Lee, Jeeyun -
Shin, Sang Joon -
Chung, Ik Joo -
Kim, Tae Won -
Chun, Hoo-Geun -
Shin, Dong Bok -
Kim, Yeul Hong -
Song, Hong Suk -
Han, Sae-Won -
Kim, Jong Gwang -
Kim, Sun Young -
Choi, Young Jin -
Chung, Hyun Cheol -
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.
Colorectal cancer Chemotherapy TSU-68
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/adverse, C-Reactive Protein/metabolism, Colorectal Neoplasms/blood/*drug therapy, Disease-Free Survival, Drug Combinations, Female, Humans, Indoles/administration & dosage/adverse effects, Interleukin-6/blood, Interleukin-8/blood, L-Lactate Dehydrogenase/blood, Male, Middle Aged, Organoplatinum Compounds/administration & dosage/adverse effects, Oxonic Acid/administration & dosage/adverse effects, Platelet-Derived Growth Factor/metabolism, Propionates/administration & dosage/adverse effects, Proto-Oncogene Proteins c-sis/blood, Tegafur/administration & dosage/adverse effects, Vascular Cell Adhesion Molecule-1/blood, Vascular Endothelial Growth Factor A/blood

주제명(Target field)
연구참여(Sample size)
질병특성(Condition Category)
연구설계(Study Design)
중재방법(Intervention Type)
중재명칭(Intervention Name)
TSU-68 + SOX did not result in a significant prolongation of PFS compared to SOX alone, but a favorable safety profile.
연구비지원(Fund Source)
근거수준평가(Evidence Hierarchy)
ICD 03