Abraxane and gemcitabine for pancreatic cancer

Abraxane (nab-paclitaxel) is an albumin-bound, 130-nm particle form of paclitaxel that was developed to avoid cremophor/ethanol-associated toxicities associated with the parent compound. Abraxane is FDA-approved for the treatment of breast cancer after the failure of combination chemotherapy for metastatic disease or relapse within 6 months. Clinical data in the prevailing peer-reviewed published medical literature is not adequate to conclude that nab-paclitaxel (abraxane) is effective for the treatment of metastatic pancreatic cancer.

There was a study of 44 patients presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago in 2010. These findings were discussed during a keynote address by Daniel Von Hoff, M.D., "Epithelium and Stroma: Double Trouble," during the "Progress in Pancreatic Cancer" session on April 18 at the 101st Annual Meeting of the American Association for Cancer Research (AACR) being held in Washington, D.C. the median overall survival (OS) time was 12.2 months, a doubling of survival compared to historical control of gemcitabine administered alone. This combination of nab-paclitaxel and gemcitabine also resulted in a confirmed overall response rate in 50 percent of patients treated, and a disease control rate (CR, PR and stable disease for 16 weeks or longer according to RECIST criteria) of 68 percent. In the overall study (n=67), three patients achieved a complete response.

There was as well a small phase II trial presented at ASCO 2010. One of 19 patients (5.3%) achieved partial response.

In 2009, Abraxane for Injectable Suspension (paclitaxel albumin [human]-bound particles for injectable suspension) was granted orphan status for the treatment of pancreatic cancer and Stage IIB-IV melanoma. An orphan designation means only that the FDA sees a need to investigate a drug for a specified indication. A Phase III study had been opened that will evaluate ABRAXANE plus gemcitabine versus gemcitabine alone as a first line therapy for advanced metastatic pancreatic cancer.

However, on 3/2/11 NCCN updated its principles of chemotherapy guideline(PANC-6) to include gemcitabine + nab-paclitaxel (Abraxane) as a category 2B recommendation for the management of locally advanced unresectable and metastatic disease in patients with good performance status.

There are few good options for pancreatic cancer patients who had received gemcitabine. They include Xeloda, Folfox, Folfirinox and possibly GTX, but no option has been demonstrated superior to others in second line. Folfirinox has an advantage in first line but is very toxic. With this, the NCCN listed gemcitabine/Abraxane should be considered a reasonable option.

I note an intersting recent abstract by Dr. Isacoff. It employs Continuous infusion 5-fluorouracil (5 FU), calcium leucovorin plus paclitaxel and oxaliplatin. The abstract concludes: Low-dose continuous (metronomic therapy) cytotoxic chemotherapy when combined with antiangiogenic therapy is safe and effective for patients with advanced pancreatic cancer. An expanded multi-institutional trial is being developed to confirm this single-institution experience."

W. H. Isacoff, H. A. Reber, F. M. Purcell, B. M. Clerkin, K. M. Clerkin; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA; University of Colorado, Boulder, CO  Low-dose continuous infusion 5-fluorouracil combined with weekly leucovorin, nab-paclitaxel, oxaliplatin, and bevacizumab for patients with advanced pancreatic cancer: A pilot study. J Clin Oncol 28, 2010 (suppl; abstr e14545) 

Hosein PJ, Pastorini VH, Gomez CM, Macintyre J, Merchan JR, Ferrell A, et al.A phase II trial of nab-paclitaxel (NP) in patients with advanced pancreatic cancer (PC) who have progressed on gemcitabine-based therapy. 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No. 214.

Von Hoff DD, et al. Promising clinical activity of a NAB paclitaxel plus gemcitabine combination in a disease-specific Phase I trial in patients with advanced pancreatic cancer. 2008 annual meeting of the American Association for Cancer Research. Abstract 4179.

Hosein PJ, Pastorini VH, Gomez CM, Macintyre J, Merchan JR, Ferrell A, et al.A phase II trial of nab-paclitaxel (NP) in patients with advanced pancreatic cancer (PC) who have progressed on gemcitabine-based therapy. 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No. 214.

Revised July 13, 2011

Comments

[Alisha Lopej]

Abraxane and gemcitbine are effective. The pancreatic cancer is a malignant neoplasm of the pancreas. These tumors have a completely different diagnostic and therapeutic profile and generally a more favorable prognosis. The treatment of a cancer patient is not easy but surgery is also very helpful in this stage.
http://www.biblehealth.com/pancreatic-cancer/pancreatic-cancer-surgery.html

[Ruby Osorio]

Thank you for your valuable post.

We have decided to share it with our global physician audience at PhysicianNexus.com: http://physiciannexus.com/forum/topics/abraxane-and-gemcitbine-for

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