Combination therapy of imatinib mesylate and interferon-alpha demonstrates minimal activity and significant toxicity in metastatic renal cell carcinoma: results of a single- institution phase II trial.
BACKGROUND
Renal cell carcinoma (RCC) is characterized by increased expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF)-beta, both of which contribute to its angiogenic phenotype. Interferon-alpha (IFN-alpha) improves survival in patients with metastatic RCC, perhaps partly because of its antiangiogenic properties. Imatinib mesylate inhibits PDGF-mediated signal transduction and might thus have antiangiogenic activity as well.


METHODS
Patients with metastatic RCC were treated with IFN-alpha (9 million IU subcutaneously 3 times weekly) and oral imatinib mesylate (600 mg daily starting on day 8). Therapy was continuous, and response was evaluated at 8-week intervals using the Response Evaluation Criteria in Solid Tumors. Baseline plasma PDGF-AA, PDGF-AB, and PDGF-BB levels were obtained.


RESULTS
Between January 2003 and January 2005, 17 patients were treated. One patient (6%) had a partial response, 4 (24%) had stable disease, 7 (41%) had progressive disease, and 5 (29%) were unevaluable because of early withdrawal secondary to toxicity. Median time to progression (TTP) using the Kaplan-Meier method was 8 weeks, and median overall survival was 17.8 months. Six patients (35%) withdrew from therapy because of toxicity, and 9 patients (53%) experienced > or = 1 grade 3/4 toxicity. Platelet-derived growth factor AA, AB, and BB plasma levels did not correlate with TTP or overall survival.


CONCLUSIONS
Based on a response rate of only 6%, a median TTP of 2 months, and significant toxicities, further study of IFN-alpha in combination with imatinib mesylate is not recommended in patients with metastatic RCC.
Polite
Blase N
BN
Section of Hematology-Oncology, Department of Medicine, University of Chicago, IL 60637, USA.
Desai
Apurva A
AA
Manchen
Beth
B
Stadler
Walter M
WM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D000068877:Imatinib Mesylate