Activity of a multitargeted, metronomic, and maximum-tolerated dose "chemo-switch" regimen in metastatic renal cell carcinoma (m

Average: 8 (1 vote)

Sub-category: Kidney Cancer

Category: Genitourinary Cancer

Meeting: 2009 ASCO Annual Meeting


Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 5040)

Abstract No: 5040

Author(s): J. Bellmunt, J. Trigo, E. Calvo, J. Carles, J. Perez-Gracia, J. Rubió, J. Virizuela, R. López, M. Lázaro, J. Albanell; University Hospital del Mar, Barcelona, Spain; Hospital Universitario Virgen de la Victoria, Malaga, Spain; University Hospital Valle Hebron, Barcelona, Spain; Clinica Universitaria de Navarra, Pamplona, Spain; Hospital Universitari Josep Trueta, Girona, Spain; Hospital Virgen Macarena, Sevilla, Spain; Hospital Clinico Universitario, Santiago de Compostela, Spain; Complejo Hospitalario Universitario de Vigo, Vigo, Spain



Background: Maximal tolerated dose (MTD) chemotherapy followed by metronomic chemotherapy (low doses administered on a frequent schedule) acts on tumor vascular endothelial cells and enhances the antitumor effect of anti-angiogenic agents (Pietras et al. J Clin Oncol. 2007). This study investigated treatment of mRCC with Gem at MTD combined with metronomic Cap and the multikinase inhibitor sorafenib.


Methods: Eligible patients had cytologically or histologically confirmed mRCC, Eastern Cooperative Oncology Group (ECOG) performance status ?1 and no previous targeted therapy or chemotherapy, and were unsuitable for or intolerant to immunotherapy. Treatment consisted of six 3-week cycles of Gem 1000 mg/m2 i.v. (days 1 and 8), oral Cap 500 mg/m2 b.i.d. (days 1 to 14) and oral sorafenib 400 mg b.i.d. (every day), followed by sorafenib monotherapy (at the discretion of the investigator). Study endpoints included median progression-free survival (PFS, primary endpoint), disease control rate according to Response Evaluation Criteria in Solid Tumors, and safety.


Results: Forty patients were enrolled and received at least one dose of treatment (median age 63 yrs, male n = 24, ECOG 0/1 n = 18/22, 1-2/>2 metastatic sites n = 31/9). Median duration of treatment was 6 months. Among 36 evaluable patients, 17 (47%) had a partial response and 17 (47%) achieved stable disease. Median PFS was 10.2 months (95% CI 7.6, 20.5). The most common adverse events (AEs) were fatigue/asthenia (78%) hand-foot syndrome (75%) and mucositis (69%). Most AEs were grade1/2, no grade 4 toxicities occurred. One patient had grade 5 dyspnea; 6 patients discontinued treatment for AEs.


Conclusions: PFS and objective responses in this study were greater than those observed in previous studies with Gem and Cap or sorafenib monotherapy in patients with mRCC, while AEs remained moderate in the majority of patients. These findings confirm the synergistic activity of the "chemo-switch" concept seen in preclinical models. The combination of sorafenib with MTD Gem and metronomic Cap warrants further investigation in mRCC.