Regorafenibi yeniden değerlendirmek: Tam doza ihtiyacımız var mı?

Öz

Amaç: Regorafenib, metastatik kolorektal kanser (mKRK) için standart bir tedavi olup genellikle 160 mg/gün dozunda uygulanmaktadır. Bu çalışma, regorafenibin düşük dozlarının etkinliğini ve yan etkilerini standart dozla karşılaştırmayı amaçlamaktadır. Gereç ve Yöntemler: Toplam 58 mKRK hastası, düşük doz (≤120 mg/gün) ve yüksek doz (>120 mg/gün) olmak üzere iki gruba ayrılmıştır. Hastalık kontrol oranı (DCR), progresyonsuz sağkalım (PFS), genel sağkalım (OS) ve yan etkiler (AEs) değerlendirilmiştir. Bulgular: Çalışmaya 58 hasta dahil edilmiş olup medyan yaş 57’dir. Regorafenib, medyan dördüncü basamak tedavi şeklinde uygulanmış; düşük doz grubunda 34, yüksek doz grubunda ise 24 hasta yer almıştır. Tüm kohortta hastalık kontrol oranı %37,9 olup gruplar arasında anlamlı bir fark saptanmamıştır (%35,3'e karşı %41,7, P=0.625). Medyan PFS [3,3 ay (95% CI: 2,2-4,3) ve 4,1 ay (95% CI: 2,3-5,8), P=0.695] ve OS [7,8 ay (95% CI: 5,8-9,7) ve 10,3 ay (95% CI: 5,1-15,5), P=0.213] gruplar arasında benzer bulunmuştur. Yan etkiler tüm kohortta %89,6 oranında görülmüştür ve yüksek doz grubunda doz azaltımı veya tedavi kesilme oranı belirgin olarak daha yüksek bulunmuştur (%41,7'ye karşı %11,8, P=0.013). Sonuçlar: Daha düşük dozlarda (≤120 mg/gün) uygulanan regorafenib, standart doz ile benzer etkinlik ve hastalık kontrol oranları sağlamaktadır. Standart doz regorafenib daha zor tolere edilmektedir. Bu sonuçlar, düşük doz uygulamasının daha iyi tedavi tolerasyonu ile, standart doza alternatif olabileceğini göstermektedir.

Anahtar Kelimeler

• kolorektal kanser
• doz yanıt ilişkisi
• ilaç toleransı

Reevaluating regorafenib: Do we need the full dose?

Öz

Aim: Regorafenib is a standard treatment for metastatic colorectal cancer (mCRC), typically administered at a dose of 160 mg/day. This study evaluates the efficacy and tolerability of lower doses of regorafenib compared to the standard dose. Material and Methods: A total of 58 mCRC patients were divided into two groups: low-dose (≤120 mg/day) and high-dose (>120 mg/day). We assessed disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Dose modifications and treatment discontinuations were recorded. Results: 58 patients with a median age of 57 years were included. Regorafenib was administered as a median fourth-line treatment, with 34 patients in the low-dose group and 24 in the high-dose group. Disease control rates were 37.9%, with no significant difference between low-dose and high-dose groups (35.3% vs. 41.7%, P=0.625). Median PFS was similar between the groups [3.3 months (95% CI: 2.2-4.3) vs. 4.1 months (95% CI: 2.3-5.8), P=0.695]. OS was also comparable across groups [7.8 months (95% CI: 5.8-9.7) vs. 10.3 months (95% CI: 5.1-15.5), P=0.213]. AEs were reported in 89.6% of patients, with a significantly higher rate of dose reductions or discontinuations in the high-dose group (41.7% vs. 11.8%, P=0.013). Conclusion: Lower doses of regorafenib (≤120 mg/day) provide comparable efficacy and similar disease control rates to the standard dose. The high-dose regimen is associated with greater tolerability issues, suggesting that lower doses may be a viable alternative for better patient management.

Anahtar Kelimeler

• colorectal cancer
• dose response relationship
• drug tolerance

Kaynakça

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