Clinical Outcomes for Patients with Metastatic Renal Cell Carcinoma Treated with Alternative Sunitinib Schedules

Abstract

Purpose To identify sunitinib alternative schedules (AS) that maintained dose intensity while decreasing adverse events (AEs) in patients with metastatic renal cell cancer (mRCC), and to determine impact of AS on clinical outcomes. Patients and Methods A retrospective review of patients ≥ 18 yr of age with clear-cell mRCC who received first-line sunitinib between 1/26/06 and 3/1/11 at a major Comprehensive Cancer Center. Subset of patients switched at first intolerable AE from traditional schedule (28 d on, 14 d off; TS) to 14 d on/7 d off schedule or other AS. Control group underwent standard dose reduction. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of PFS and OS were analyzed using Cox regression. Results One hundred eighty five patients were included for analysis; 87% were on TS at baseline. During treatment, 53% of patients continued TS and 47% initiated or transitioned to AS. Baseline characteristics were similar. AEs prompting schedule modification included fatigue (64%), hand-foot syndrome (38%) and diarrhea (32%). Median time to AS was 5.6 mo. Median OS was 17.7 mo (95% confidence interval [CI], 10.8-22.2) on TS compared to 33.0 mo (95% CI, 29.3- not estimable) on AS (P < 0.0001). By multivariable analysis; poor ECOG PS, increased LDH, decreased albumin, unfavorable Heng criteria, and TS are associated with decreased OS (P < 0.05). Conclusion Sunitinib administered on AS may mitigate AEs and has comparable outcomes as TS for mRCC patients. Prospective investigations of alternate dosing schemas are warranted.

Alternate sunitinib schedules in patients with metastatic renal cell carcinoma

“…By multivariate analysis, poor ECOG PS, increased LDH, decreased albumin, unfavorable Heng criteria and conventional schedule were associated with decreased OS (P < 0.05). Comparison of toxicity prevalence before and after schedule adjustment demonstrated a clear reduction in toxicity rates [16]. The prevalence of the more common AEs such as fatigue, HFS and diarrhea at the first follow-up after schedule modification dropped to 29%, 10% and 6%, respectively.…”

Possibilities of using alternative schemes of sunitinib therapy in patients with metastatic renal cell carcinoma

“…Большин-ство опубликованных исследований посвящено сравнению режима 4 / 2 с режимом 2 / 1 (2 недели ежедневного прие-ма сунитиниба в дозировке 50 мг с последующим недель-ным перерывом). Был опубликован ряд ретроспективных исследований, в которых было показано преимущество в уменьшении частоты побочных явлений при назначении режима 2 / 1 над традиционным режимом 4 / 2 [14][15][16][17][18][19][20][21][22].…”

“…В ретроспективном одноцентровом исследовании [15] были проанализированы результаты лечения пациентов с метастатическим светлоклеточным ПКР у пациентов старше 18 лет, которым сунитиниб назначался в качестве первой линии терапии. В исследуемую группу были вклю-чены пациенты, у которых вследствие побочных эффек-тов возникла необходимость изменить стандартную схему 4 / 2 на 2 / 1 или другую схему.…”

“…Медиана времени до смены схемы лечения составила 5,6 месяцев. Выживаемость в груп-пе стандартного лечения составила 17,7 месяцев, в группе альтернативного лечения -33,0 месяца (p<0,0001) [15].…”

Optimization of sequential targeted therapy

“…B. J. Atkinson и соавт. при-шли к выводу, что сунитиниб в альтернативном ре-жиме дозирования может снизить частоту развития НЯ и увеличить эффективность лечения пациентов с мПКР [18].…”