Shoichi Hazama1, Hiromichi Maeda2, Shigeyoshi Iwamoto3, Ho Min Kim4, Hiroyoshi Takemoto5, Kenji Kobayashi6, Junichi Sakamoto7, Naoki Nagata8, Koji Oba9, Hideyuki Mishima10. 1. Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University, Graduate School of Medicine, Ube, Japan. 2. Cancer Treatment Center, Kochi University, Nankoku, Japan. Electronic address: hmaeda@kochi-u.ac.jp. 3. Kansai Medical University Hirakata Hospital, Hirakata, Japan. 4. Division of Surgery, Osaka Rosai Hospital, Sakai, Japan. 5. Department of Surgery, Kinki Central Hospital, Itami, Japan. 6. Department of Surgery, Matsunami General Hospital, Hashima, Japan. 7. Tokai Central Hospital, Kakamigahara, Japan. 8. Kitakyushu General Hospital, Kitakyushu, Japan. 9. Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 10. Cancer Center, Aichi Medical University, Nagakute, Japan.
Abstract
BACKGROUND: Despite the comparable clinical benefit of XELOX (capecitabine with oxaliplatin) and FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), the value of XELOX treatment in combination with cetuximab for metastatic colorectal cancer (mCRC) remains largely unknown. PATIENTS AND METHODS: In this clinical trial we evaluated the efficacy and safety of weekly/biweekly cetuximab administration combined with biweekly XELOX in patients with previously untreated v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type mCRC. The primary end point was response rate (RR) with confirmation, and the secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), dose intensity, and the safety of the protocol treatment. RESULTS: Forty patients who fulfilled the inclusion criteria participated in this study. The median treatment cycle number was 8 and the median dose intensities were 218 mg/m2/wk for cetuximab, 34 mg/m2/wk for oxaliplatin, and 821 mg/m2/d for capecitabine. One patient showed complete response and partial response was observed in 19 patients, giving an overall RR of 50% (95% confidence interval [CI], 33.8%-66.2%). Stable disease was obtained in 13 patients, resulting in a DCR of 82.5% (95% CI, 67.2%-92.7%). The PFS was 6.5 months (95% CI, 3.5-9.6 months), and the OS was 24.3 months (95% CI, 14.9-33.7 months). The safety profile revealed the common Grade 3/4 adverse events to be acneiform eruption (12.5%), peripheral neuropathy (7.5%), and elevated alanine transaminase levels (7.5%). Grade 3/4 thrombocytopenia and neutropenia occurred only in 5.0% and 2.5% of the patients, respectively. Grade 1 hand-foot syndrome (HFS) was not uncommon (20%), whereas Grade 2/3 HFS occurred in only 3 patients (7.5%). No deaths were reported within 30 days of the last dose. CONCLUSION: Cetuximab with XELOX showed a confirmed overall RR of 50%, which was within the previously reported range of RR. The safety profile showed an acceptable rate and severity of adverse events. In light of the several advantages of XELOX, including convenience and the reported cost-saving aspects, further study of this combination therapy is warranted. Copyright Â
BACKGROUND: Despite the comparable clinical benefit of XELOX (capecitabine with oxaliplatin) and FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), the value of XELOX treatment in combination with cetuximab for metastatic colorectal cancer (mCRC) remains largely unknown. PATIENTS AND METHODS: In this clinical trial we evaluated the efficacy and safety of weekly/biweekly cetuximab administration combined with biweekly XELOX in patients with previously untreated v-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog (KRAS) wild type mCRC. The primary end point was response rate (RR) with confirmation, and the secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), dose intensity, and the safety of the protocol treatment. RESULTS: Forty patients who fulfilled the inclusion criteria participated in this study. The median treatment cycle number was 8 and the median dose intensities were 218 mg/m2/wk for cetuximab, 34 mg/m2/wk for oxaliplatin, and 821 mg/m2/d for capecitabine. One patient showed complete response and partial response was observed in 19 patients, giving an overall RR of 50% (95% confidence interval [CI], 33.8%-66.2%). Stable disease was obtained in 13 patients, resulting in a DCR of 82.5% (95% CI, 67.2%-92.7%). The PFS was 6.5 months (95% CI, 3.5-9.6 months), and the OS was 24.3 months (95% CI, 14.9-33.7 months). The safety profile revealed the common Grade 3/4 adverse events to be acneiform eruption (12.5%), peripheral neuropathy (7.5%), and elevated alanine transaminase levels (7.5%). Grade 3/4 thrombocytopenia and neutropenia occurred only in 5.0% and 2.5% of the patients, respectively. Grade 1 hand-foot syndrome (HFS) was not uncommon (20%), whereas Grade 2/3 HFS occurred in only 3 patients (7.5%). No deaths were reported within 30 days of the last dose. CONCLUSION:Cetuximab with XELOX showed a confirmed overall RR of 50%, which was within the previously reported range of RR. The safety profile showed an acceptable rate and severity of adverse events. In light of the several advantages of XELOX, including convenience and the reported cost-saving aspects, further study of this combination therapy is warranted. Copyright Â
Authors: George Papaxoinis; Vassiliki Kotoula; Eleni Giannoulatou; Georgia-Angeliki Koliou; Vasilios Karavasilis; Sotirios Lakis; Andreas Koureas; Mattheos Bobos; Elpida Chalaralambous; Emily Daskalaki; Kyriakos Chatzopoulos; George Tsironis; Elisavet Pazarli; Sofia Chrisafi; Epaminontas Samantas; Ioannis G Kaklamanos; Ioannis Varthalitis; Athina Konstantara; Konstantinos N Syrigos; George Pentheroudakis; Dimitrios Pectasides; George Fountzilas Journal: Med Oncol Date: 2018-05-31 Impact factor: 3.064