A Randomized Phase 2 Trial of Bevacizumab with or without Daily Low-Dose Interferon Alfa-2b in Metastatic Malignant Melanoma

Abstract

Bev was well tolerated at this dose and prolonged disease stabilization was achieved in one-quarter of metastatic melanoma patients. Low-dose IFN-alpha2b did not augment the activity of Bev.

Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts

“…These observations, together with the results of clinical trials using antiangiogenic agents (Yang et al, 2003;Hurwitz et al, 2004;Miller et al, 2005a, b;Motzer and Bukowski, 2006;Varker et al, 2007) suggest a more complex impact of this treatment modality than previously anticipated. In most current clinical studies, antiangiogenic agents are used as adjuvant therapy in combination with chemotherapy or sometimes chemoradiotherapy.…”

“…Interestingly, addition of bevacizumab to first-line chemotherapy in patients with metastatic colorectal cancer increased response rates and prolonged overall survival (Hurwitz et al, 2004). Nevertheless, the response to these drugs varied significantly among patients, and in all studies performed to date numerous patients underwent an antiangiogenic regimen without apparent significant benefit in survival or time to progression (Yang et al, 2003;Miller et al, 2005a, b;Motzer and Bukowski, 2006;Varker et al, 2007). Therefore, it is important that we understand the causes of this variable drug response and discover the molecular indicators of individual response to antiangiogenic therapy to select an optimal regimen for each individual.…”

“…The extent of angiogenesis is frequently related to cancer progression and in some cases may predict the probability of metastasis (Srivastava et al, 1988;Weidner et al, 1991). This linkage paved the way to clinical trials with antiangiogenic agents, which in some cases have dramatically changed the standards of care (Miller et al, 2005a, b;Motzer and Bukowski, 2006;Varker et al, 2007). In particular, bevacuzimab/avastin, a humanized monoclonal-neutralizing antibody directed against vascular endothelial growth factor has since 2004 become incorporated into the first-line therapies in metastatic colorectal carcinoma (CRC) (Hurwitz et al, 2004) and other malignancies (Gasparini et al, 2005).…”

Angiogenesis in cutaneous disease: Part II

“…In a randomized phase II trial, bevacizumab (15 mg/kg IV every 2 weeks) was administered with and without daily low-dose IFNa2b (1 MU/m 2 subcutaneously daily), an inhibitor of bFGF. 31 Bevacizumab prolonged disease stabilization in about 25% of the patients (8/36); however lowdose IFNa2b did not augment the activity of bevacizumab. Bevacizumab (5 mg/kg) in combination with chemotherapeutic agents cisplatin/carboplatin or fotemustine achieved disease regression in two out of three patients after three courses of therapy.…”

Immunotargeting of Melanoma

“…Its effectiveness has been proven in the treatment of colon and kidney cancer (Saltz et al, 2008, Melichar et al, 2008. In the treatment of advanced melanoma its efficacy was evaluated in combination with low dose interferon-alfa-2b in a phase II trial which did not show extension of survival in studied patients (Varker et al, 2007). In another phase II trial enrolling 62 metastatic melanoma patients, the effectiveness of bewacizumab in combination with temozolomide was tested.…”