Abraxane and Avastin for Ovarian Cancer – pro

Paclitaxel is one of the most active agents in the treatment of ovarian carcinoma. Novel agents such as abraxane are solvent free and currently being evaluated to potentially avoid certain patient side effects. Abraxane is an albumin-stabilised nanoparticle formulation of paclitaxel designed to overcome various insolubility problems encountered with paclitaxel. This nano-technology eliminates the need for toxic solvents like cremophor, which limits the dose of paclitaxel that can be administered and hence affect overall drug efficacy. Cremophor is also know to cause various types of allergic reactions in patients who receive paclitaxel. Albumin receptor-mediated paclitaxel-transport mechanism is analogous to the opening of a ‘trapdoor’ on the endothelial cell wall within blood vessels. This facilitates easy passage of abraxane from the bloodstream via the blood vessels to the underlying tumour tissue. Abraxane appears active for ovarian cancer but it remain under study. Results of a Phase II evaluation of nanoparticle albumin bound paclitaxel (nab-paclitaxel) in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer (Abstract 5525)in May 2007 ASCO. NCCN lists it for salvage therapy of relapsed ovarian cancer.

Avastin appears to add to combination chemotherapies for ovarian cancer.  Researchers from California recently conducted a study to further evaluate the effectiveness of Avastin for treatment of recurrent ovarian cancer. This trial included 33 patients who had received extensive prior chemotherapy. Treatment with Avastin was generally well tolerated with some responses.

This is the 3rd positive phase II trial. The previous trials included Avastin with metronomic cyclophosphamide and one with a taxane. A phase III trial, however, was stopped by Genetech when an unexpected 11% of participants developed bowel perforations. The debate about why this happened and how it was related to the patient characteristics still has not been resolved. Nevertheless, based on the existing evidence, NCCN has now added Avastin to its list of recommended drugs for ovarian cancer. Phase III trials are now in progress to determine the role of this drug in primary therapy as an adjunct to platinum-taxane chemotherapy.

Researchers from Ohio State University evaluated Avastin plus chemotherapy with Taxol® (paclitaxel) or Taxotere® (docetaxel) in 10 patients with advanced, recurrent, refractory ovarian cancer. The nine patients with available information all experienced a decline in serum CA125 levels. After a median of three cycles of therapy, five patients have had an increase in CA125 levels while three had normalization of levels and another has had continued improvement. Treatment provided relief of pain, nausea, and accumulation of fluid in the abdomen (ascites).Several confirmatory abstracts of taxanes with Avastin in pre-treated population have been presented in various meetings in 2007 and 2008. NCCN lists Avastin in its list of recommended treatments.

The most recent study was presented in 2010 ASCO meeting. 48 patients who had recurrent platinum-resistant OC (93.7%) or primary peritoneal carcinoma with measurable disease (by CT/MRI) were enrolled. 19 (40%) patients had one prior regimen, 27 (56%) had two prior regimens, and 2 (4%) patients had more than two prior regimens. All patients received nab-paclitaxel 100 mg/m2 IV on days 1, 8, 15 with bevacizumab 10 mg/kg IV given on days 1 and 15 every 28 days, and were treated until progression.. The median PFS, with 37 of 48 patients having experienced disease progression or death, was 8.3 months. Median OS was 16.5 months. Best overall response for the 39 patients who have completed the study to date: partial response: 18 (46.1%); stable disease: 12 (30.8%), progressive disease: 8 (20.5%), and not evaluable: 1 (2.6%). The rate of adverse events was low with 10% of the events reported as grade 3 or 4 toxicities. These were encouraging results in a situation where no standard therapy exists.

Update: Avastin found effective in first line – see here

Micha JP, ET AL, Abraxane in the treatment of ovarian cancer: the absence of hypersensitivity reactions. : Gynecol Oncol. 2006 Feb;100(2):437-8. Epub 2005 Oct

Abraxane, Prescribing information

NCCN.ORG, Ovarian Cancer, 2012

Monk B, Han E, Josephs-Cowan C, et al. Salvage Bevacizumab (rhuMAB VEGF)-based Therapy after Multiple Prior Cytotoxic Regimens in Advanced Refractory Epithelial Ovarian Cancer. Gynecologic Oncology. 2006; 102: 140-144.

Bidus MA, Webb JC, Seidman JD, et al. Sustained response to bevacizumab in refractory well-differentiated ovarian neoplasms.Gynecologic Oncology. 2006;May 11

Cohn DE, Valmadre S, Resnick KE, et al. Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Gynecologic Oncology. 2006;March 7

Robert A. Burger, Eperience With Bevacizumab in the Management of Epithelial Ovarian Cancer,  Journal of Clinical Oncology, Vol 25, No 20 (July 10), 2007: pp. 2902-2908

Robert A. Burger, M.D., Mark F. Brady, Ph.D., Michael A. Bookman, M.D., Gini F. Fleming, M.D., Bradley J. Monk, M.D., Helen Huang, M.S., Robert S. Mannel, M.D., Howard D. Homesley, M.D., Jeffrey Fowler, M.D., Benjamin E. Greer, M.D., Matthew Boente, M.D., Michael J. Birrer, M.D., Ph.D., and Sharon X. Liang, M.D. for the Gynecologic Oncology Group Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer N Engl J Med 2011; 365:2473-2483

Cohn DE, Valmadre S, Resnick KE, et al. Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Gynecologic Oncology. 2006;March 7;

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