Randomized Phase II Trial of Sunitinib on an Intermittent Versus Continuous Dosing Schedule As First-Line Therapy for Advanced Renal Cell Carcinoma

Abstract

Median time to tumor progression was 9.9 months for schedule 4/2 and 7.1 months for the CDD schedule (hazard ratio, 0.77; 95% CI, 0.57 to 1.04; P = .090). No significant difference was observed in overall survival (23.1 v 23.5 months; P = .615), commonly reported adverse events, or patient-reported kidney cancer symptoms. Schedule 4/2 was statistically superior to CDD in time to deterioration, a composite end point of death, progression, and disease-related symptoms (P = .034). CONCLUSION; There was no benefit in efficacy or safety for continuous dosing of sunitinib compared with the approved 50 mg/d dose on schedule 4/2. Given the numerically longer time to tumor progression with the approved 50 mg/d dose on schedule 4/2, adherence to this dose and schedule remains the treatment goal for patients with advanced RCC.

Alternate sunitinib schedules in patients with metastatic renal cell carcinoma

“…A recent randomized phase II study comparing a 37.5-mg CDD regimen to the 4/2 schedule (EFFECT trial) demonstrated no differences in drug tolerance or patient-reported symptoms, but showed a trend toward superiority of the 4/2 schedule over CDD in time to tumor progression (9.9 months for 4/2 schedule versus 7.1 months for CDD, HR 0.77, 95% CI 0.57-1.04, P = 0.09). No significant difference was observed in the OS (23.1 months for the 4/2 schedule versus 23.5 months for CDD, P = 0.615) [5].…”

“…In a study by Wong et al, fatigue and diarrhea were the most troublesome toxicities for patients, and patients were willing to forego 4.4 months of PFS to ameliorate their symptoms from severe to mild-to-moderate [9]. Interestingly, with the standard 4-week treatment followed by a 2-week break, a cyclic scoring pattern is observed in patient-reported quality-of-life indicators; with improvement in mean scores after the 2-week treatment break [5].…”

“…In the original phase III trial of sunitinib, 38% and 32% patients in the sunitinib arm underwent dose interruptions and reductions, respectively, because of drug toxicity [4]. In clinical practice, it is often noted that AEs increase throughout each cycle, and tend to be worst in the final 2 weeks of treatment cycle [5]. The impact of treatment-related toxicities on patients can be significant and, for some patients, living longer may not always equate with living better.…”

Advanced renal cell carcinoma in Australia, 2015: What should we do?

“…Recognition that symptoms recur rapidly during the treatment break might suggest that a continuous regimen might be preferable. Continuous treatment with sunitinib does not seem to have benefits over the 4/2 regimen, 13 so perhaps this patient might be better switched to continuous pazopanib. Alternatively, a patient on pazopanib with cumulative toxicity but a history of a previously slowly growing cancer might find the 2-week treatment break of the 4/2 sunitinib regimen to be a welcome relief.…”

Böbrek Hücreli Karsinomlu Hastaların Demografik Özellikleri ve Tedavi Sonuçları: Tek Merkez Deneyimi

“…Klinik çalışmalarda sunitinible tedavi edilen hastalarda GS 18,40 ile 26,40 ay arasında iken, PS 9,90 ile 11 ay arasındaydı. 8,14,29,30 Biz bu çalışmada, ortanca GS ve PS'leri bu klinik çalışmalara göre daha yüksek bulduk. Bu sonuçlara, bizim çalışma grubumuzda hasta sayısının az olması ve bu hastaların çoğunluğunun iyi ve orta risk grubunda olmasının katkısının olabileceğini düşünüyoruz.…”