A phase II trial of gemcitabine(G), capecitabine (C), and bevacizumab (B) in patients (pts) with metastatic renal cell carcinoma (RCC)

Abstract

e16072 Background: RCC is resistant to most traditional DNA and DNA repair targeted chemotherapy; although modest response rates to nucleotide analog based therapy, including GC, have been reported. Bevacizumab has activity in RCC. We thus performed a single center phase II trial of GCB in pts with metastatic RCC. Methods: Eligibility included clear cell or unclassified histologies, performance status 0–1, measurable disease, normal organ function and no prior treatment with VEGF binding agents or pyramidine analogs. Following significant hematotoxicity in the first 7 of 8 pts, chemotherapy was modified to G 1,000 mg/m2 (days 1, 8), C 1,000 mg po bid (days 1–14) and B 15 mg/kg (day 1) on a 21 day cycle with disease re-evaluation every 3 cycles. Primary endpoint was objective response rate (ORR) using a Bayesian continuous reassessment method designed to detect an improvement in the ORR from a 15% historical rate to 27%. Maximum planned enrollment = 55. Results: 30 pts enrolled from March 2005-May 2008 of which 29 were evaluable: 1 never treated. Pt characteristics: male 83%, median age 58 (36–82), prior nephrectomy 83%, prior radiation 52%, prior cytokine therapy 28%, prior VEGFR tyrosine kinase inhibitor 69%. MSKCC prognostic group: good 24%, intermediate 66%, poor 10%. 7 pts had a partial response (24%). Median overall and progression free survival were 9.8 mo (95%CI: 6.2, 14.9) and 5.3 mo (95%CI: 3.9, 9.9). Grade 3 or 4 toxicities: leucopenia 17%, neutropenia 31%, thrombocytopenia 7%, anemia 14%, proteinuria 3%, rash/hand foot syndrome 7%, fatigue 21%. Average change in mean arterial pressure after 2 cycles: 5.6 (p = 0.040). Serious adverse events: bowel perforation resulting in death 1 pt (3%), sepsis 1 pt (3%), PE/DVT 3 pts (10%), seizure 1 pt (3%). Conclusions: The trial was terminated early despite not meeting protocol criteria for success or futility due to slow accrual and the fact that the historical response rate on which the trial was based became irrelevant with emerging data using sequential VEGF pathway directed therapies. Nevertheless, the observed progression free and overall survival compare favorably to other phase II trials in this population. [Table: see text]