Phase II presurgical feasibility study of bevacizumab in untreated patients with metastatic renal cell carcinoma.
OBJECTIVE
To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy.


METHODS
Patients with newly diagnosed, clear cell mRCC whose primary tumors were considered resectable were enrolled. In this single-arm, phase II trial, patients received bevacizumab plus erlotinib (first patients, n = 23) or bevacizumab alone (n = 27 patients) for 8 weeks followed by restaging. If patients demonstrated progressive disease and had declining performance statuses after 8 weeks, nephrectomy procedures were deferred. Postoperatively, patients continued on the study drug or drugs if disease stabilization or regression had occurred.


RESULTS
Between March 2005 and March 2008, 52 patients were enrolled on study, and 50 were included in the analysis. By Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk, features. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI, 5.5 to 15.6 months). Median overall survival was 25.4 months (95% CI, 11.4 months to not estimable). Two perioperative deaths occurred; neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients and treatment delay for two others.


CONCLUSIONS
Presurgical treatment with bevacizumab therapy yields clinical outcomes comparable to post-surgical treatment with antiangiogenic therapy in patients with mRCC, but it may result in wound-healing delays. Prospective, randomized trials to test the use of presurgical therapy as a method to select appropriate patients for cytoreductive nephrectomy are warranted.
Jonasch
Eric
E
Department ofGenitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, PO Box 301439, Houston, TX 77230-1439, USA. ejonasch@mdanderson.org
Wood
Christopher G
CG
Matin
Surena F
SF
Tu
Shi-Ming
SM
Pagliaro
Lance C
LC
Corn
Paul G
PG
Aparicio
Ana
A
Tamboli
Pheroze
P
Millikan
Randall E
RE
Wang
Xuemei
X
Araujo
John C
JC
Arap
Wadih
W
Tannir
Nizar
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009392:Nephrectomy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride