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

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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
 
Abstract:
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.