Phase II escalation study of sorafenib in patients with metastatic renal cell carcinoma who have been previously treated with anti‐angiogenic treatment

• DOI: 10.1111/j.1464-410x.2011.10421.x
• Publication Date: 2011-12-24T23:00:41Z
• Authors: Andrea Mancuso; Eugenio Donato Di...; Alvaro Leone; Alfonso Catalano; Fabio Calabrò; Linda Cerbone; Andrea Zivi; Carlo Messina; Silvia Alonso; Leonardo Vigna; Rita Caristo; Cora N. Sternberg
• Keywords: Adult; Aged, 80 and over; Diarrhea; Male; Mucositis; Niacinamide; Dose-Response Relationship, Drug; Phenylurea Compounds; Benzenesulfonates; Middle Aged; Prognosis; Disease-Free Survival; Kidney Neoplasms; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Biomarkers, Tumor; Humans; Female; Hand-Foot Syndrome; Neoplasm Metastasis; Carcinoma, Renal Cell; Aged

Study Type – Therapy (individual cohort) Level of Evidence 2b What's known on the subject? and What does study add? Sorafenib is an oral receptor tyrosine kinase inhibitor that inhibits RAF serine/threonine kinases (vascular endothelial growth factor receptors 1, 2, 3 platelet‐derived factor‐beta, Flt‐3 c‐kit) are implicated in tumourigenesis tumour progression. approved for treatment advanced renal cell cancer. B‐RAF mutations (V600E K601E) may be interesting negative predictive markers metastatic kidney cancer patients treated with Sorafenib. Larger trials needed to validate this hypothesis should include molecular analysis better patient selection. OBJECTIVE To assess both clinical biological efficacy toxicity sorafenib carcinoma (mRCC) previously anti‐angiogenic vascular (VEGFR) inhibitor. METHODS orally active multikinase mRCC. Drug‐focused translational research tissues (i.e. B‐RAF) plasma (VEGFR‐α, circulating cells, progenitor cells) was performed define prognostic their related kinetics. Patients mRCC pretreated treatment, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2 adequate organ function were eligible. received 400 mg twice a day continuously 4‐week cycles. no progressive disease at 12 weeks continued receive standard dose, whereas progressing increased dose (600 day) early restaging after 4 weeks. who progressed 600 went off study. Efficacy (overall control) assessed by Response Evaluation Criteria Solid Tumors. RESULTS In all, 19 entered. The baseline characteristics as follows: ECOG PS 0–1 94.8%; median (range) age 62 (41–81) years; nephrectomy 100%; surgery 26.4%; clear 79.1%; papillary 15.7%; sarcomatoid/high grade 5.2%; two or more sites 84%. Overall, 11 (58%) had control 6 months without significant correlation between response prior therapy hypertension. Progression‐free survival (PFS) 8.3 observed. Of six whom escalated due progression, three benefitted PFS >3 months. Three (15.7%) V600E mutation one K601E mutation; appeared substantially shorter these compared 15 wild‐type (2.5 vs 9.1 month, P < 0.05). most common (National Cancer Institute Common Toxicity Criteria, NCIC 3.0, all patients) ≥1 diarrhoea 2–3 hand–foot syndrome patients. Grade mucositis observed patient. CONCLUSIONS doses 400–600 results acceptable well tolerated salvage VEGFR failure. patients, higher could valid option marker studied larger randomized trial.