Regorafenib: start low and go slow

Regorafenib for Patients with Metastatic Colorectal Cancer Who Progressed After Standard Therapy: Results of the Large, Single-Arm, Open-Label Phase IIIb CONSIGN Study

“…Regorafenib‐related TEAEs led to dose modifications in 60% of patients but to treatment discontinuation in only 9%, suggesting that regorafenib‐related TEAEs were managed with dose modifications, allowing patients to stay on therapy. The high rate of dose reductions observed in this study and in the phase III trials has motivated the exploration of new dosing strategies, including starting regorafenib at doses <160 mg and increasing the dose as tolerated; this approach reflects current clinical practice by some physicians . A recently reported small, randomized phase II trial ( n = 123) showed that a higher proportion of patients with mCRC starting regorafenib treatment using a rapid dose‐escalation strategy during the first cycle (starting at 80 mg daily for 1 week and escalating the daily dose by 40 mg during weeks 2 and 3 to 160 mg daily as tolerated) continued to cycle 3 compared with those starting at the 160 mg daily dose; data suggest that patients treated using the dose‐escalation strategy may have had better outcomes .…”

Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective, observational CORRELATE study

“…The starting dose of regorafenib for almost half the patients was less than the approved 160-mg daily dose. Physicians previously described starting regorafenib at doses less than 160 mg and increasing the dose as tolerated [14,15]. A recent randomised phase II trial (ReDOS) reported that weekly dose escalation from 80 mg to 160 mg during the first cycle allowed more patients to complete two cycles of treatment and initiate a third compared with starting at the approved 160-mg dose [16].…”

The real-world use of regorafenib for metastatic colorectal cancer: multicentre analysis of treatment pattern and outcomes in Hong Kong

“…Although the recommended dose of regorafenib is 160 mg daily, data from the phase I dose escalation study of regorafenib in solid tumours has shown a dose-dependent increase in systemic exposure of the parent drug up to 60 mg and a further increase was not achieved with escalation to 120 mg 11. In view of significant toxicities, Tabchi and Ghosn12 reported a ‘start low and go slow’ approach by starting regorafenib at 80 mg daily with incremental increases of 40 mg every 5 days until 160 mg daily or the occurrence of grade 2 or higher AEs. Eight of twelve patients were able to reach the dose level of 160 mg daily but complete efficacy and toxicity data were not available.…”