Per Pfeiffer1, Hafdan Sorbye2, Camilla Qvortrup3, Mia Karlberg4, Christian Kersten5, Kirsten Vistisen6, Birgitta Lindh7, Jon Kroll Bjerregaard3, Bengt Glimelius8. 1. Odense University Hospital, Odense, Denmark. Electronic address: per.pfeiffer@rsyd.dk. 2. Haukeland University Hospital, Bergen, Norway. 3. Odense University Hospital, Odense, Denmark. 4. Karolinska Institutet, Stockholm, Sweden. 5. Sørlandet Hospital, Kristiansand, Norway. 6. Herlev Hospital, Copenhagen, Denmark. 7. Umeå University, Umeå, Sweden. 8. Uppsala University, Uppsala, Sweden.
Abstract
BACKGROUND: In the NORDIC-7.5 trial, how cetuximab might safely and conveniently be added to an intermittent treatment strategy in patients with prospectively selected Kirsten rat sarcoma viral oncogene homolog wild type (KRASwt) metastatic colorectal cancer (mCRC) was investigated. Patients were treated in a multicenter phase II trial with cetuximab in combination with the Nordic bolus FLOX (oxaliplatin, 5-fluorouracil, and folinic acid) for 4 months followed by maintenance cetuximab. PATIENTS AND METHODS: Patients had KRASwt, nonresectable mCRC, no previous chemotherapy, and Eastern Cooperative Group performance status of 0 to 2. Patients received 8 courses of Nordic FLOX (oxaliplatin 85 mg/m(2) over 1 hour on day 1, and 5-fluorouracil 500 mg/m(2) as a bolus injection, followed 30 minutes later with bolus folinic acid 60 mg/m(2) on days 1 and 2). Cetuximab was administered every 2 weeks at a dose of 500 mg/m(2) for 16 weeks followed by cetuximab as maintenance therapy until disease progression. RESULTS: Between July 2008 and September 2010, 152 KRASwt patients were included. The response rate was 62% (95% confidence interval [CI], 54%-69%), median progression-free survival was 8.0 months (95% CI, 7.5-8.9) and median overall survival was 23.2 (95% CI, 18.1-27.4) months. Twenty-one patients (14%) had later R0-resection of metastasis. FLOX with cetuximab was reintroduced in 47 of 85 patients (55%). The most common Grade 3/4 nonhematologic adverse events were diarrhea in 14 patients (9%), skin rash in 13 patients (9%), infection without neutropenia in 11 patients (7%), and fatigue in 11 patients (7%). CONCLUSION: In a prospectively selected KRASwt population, biweekly cetuximab was safely integrated in an intermittent chemotherapy strategy and might have added to a longer chemotherapy-free interval. However, the combination of biweekly cetuximab with chemotherapy needs to be validated in trials using FOLFOX (oxaliplatin, fluorouracil, and leucovorin) or FOLFIRI (irinotecan, fluorouracil, and leucovorin).
BACKGROUND: In the NORDIC-7.5 trial, how cetuximab might safely and conveniently be added to an intermittent treatment strategy in patients with prospectively selected Kirsten ratsarcoma viral oncogene homolog wild type (KRASwt) metastatic colorectal cancer (mCRC) was investigated. Patients were treated in a multicenter phase II trial with cetuximab in combination with the Nordic bolus FLOX (oxaliplatin, 5-fluorouracil, and folinic acid) for 4 months followed by maintenance cetuximab. PATIENTS AND METHODS: Patients had KRASwt, nonresectable mCRC, no previous chemotherapy, and Eastern Cooperative Group performance status of 0 to 2. Patients received 8 courses of Nordic FLOX (oxaliplatin 85 mg/m(2) over 1 hour on day 1, and 5-fluorouracil 500 mg/m(2) as a bolus injection, followed 30 minutes later with bolus folinic acid 60 mg/m(2) on days 1 and 2). Cetuximab was administered every 2 weeks at a dose of 500 mg/m(2) for 16 weeks followed by cetuximab as maintenance therapy until disease progression. RESULTS: Between July 2008 and September 2010, 152 KRASwt patients were included. The response rate was 62% (95% confidence interval [CI], 54%-69%), median progression-free survival was 8.0 months (95% CI, 7.5-8.9) and median overall survival was 23.2 (95% CI, 18.1-27.4) months. Twenty-one patients (14%) had later R0-resection of metastasis. FLOX with cetuximab was reintroduced in 47 of 85 patients (55%). The most common Grade 3/4 nonhematologic adverse events were diarrhea in 14 patients (9%), skin rash in 13 patients (9%), infection without neutropenia in 11 patients (7%), and fatigue in 11 patients (7%). CONCLUSION: In a prospectively selected KRASwt population, biweekly cetuximab was safely integrated in an intermittent chemotherapy strategy and might have added to a longer chemotherapy-free interval. However, the combination of biweekly cetuximab with chemotherapy needs to be validated in trials using FOLFOX (oxaliplatin, fluorouracil, and leucovorin) or FOLFIRI (irinotecan, fluorouracil, and leucovorin).