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FDA Approval: Nab-paclitaxel in Combination with Gemcitabine for Pancreatic Cancer

On September 6th the U.S Food and Drug Administration (FDA) – per its commendable fast track expedited review program for “orphan” diseases (which now includes pancreatic cancer) has approved nab-paclitaxel (trade name: Abraxane) for use in in combination with gemcitabine for metastatic pancreatic cancer (ductal adenocarcinoma of the pancreas). The previous drug agent officially approved by the FDA for pancreatic cancer (occurred on November 2, 2005) was the targeted agent erlotinib (trade name: Tarceva) in combination with gemcitabine.

This rather remarkable rapid FDA approval stems from the outcomes of the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPAC study) presented this past January in San Francisco at the American Society of Clinical Oncology’s 2013 Gastrointestinal Cancers Symposium by Daniel Von Hoff, MD, the physician-in-chief and director of Translational Research at the Translational Genomics Research Institute.

Paclitaxel is one of the taxane family of drug agents, and available in the U.S. as Taxol, which is approved for use in the treatment of several cancers. Nab-paclitaxel has been developed by the Celgene biotech company and is formed by adding the protein molecule albumin to the drug complex. Abraxane has previously been approved by the FDA for use in metastatic breast cancer and non-small cell lung cancer.

One interesting association is that Dr. Von Hoff also led the research team that developed the work resulting in the 1996 FDA approval of gemcitabine for the treatment of pancreatic cancer.

MPAC was a multi-country, multi-center (151 community and academic centers) Phase III clinical trial involving 861 patients with previously untreated advanced pancreatic cancer who were randomly assigned to one of two arms: to receive either standard gemcitabine treatment OR to receive 125/m2 of nab-paclitaxel followed by standard gemcitabine treatment.

The MPAC patient group that was given the Abraxane/gemcitabine combined therapy demonstrated a 59% increase in the 12-month median survival rate above the group that had been treated with only gemcitabine. The Abraxane combination arm showed about a two month increase in overall survival advantage above the gemcitabine single treatment arm (8.5 months versus 6.7 months). Also, the 12-month survival rose from 22% to 35% in the group that was given the combination regimen at an impressive P=0.0002. The 2-year survival was still poor but increased with the combination to 9% from 4% over single therapy.

It would seem that the FOLFIRINOX regimen presented in 2011 and now this Abraxane/gemcitabine regimen appear to represent modest but definite advantage in the treatment of metastatic adenocarcinoma of the pancreas. Further research will undoubtedly further illuminate the nature and extent of these particular advantages – and present indications for these and single therapy (gemcitabine) as first-line treatment standard of care.


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Dale O’Brien, MD

Chemotherapy Regimen for NET: Platinum Agent Plus Topoisomerase Inhibitor

The exploration of chemotherapy for advanced pancreatic neuroendocrine tumors has been somewhat sparse, but has increased pace during the past few years. Certain of these regimens have met with some success, increasing the armamentarium of clinicians.

Beijing, China researchers led by Shen from the Peking University School of Oncology have published an article in the September 2013 issue of the journal Medical Oncology that examines the outcome of such a chemo regimen: the platinum drug cisplatin in combination with the topoisomerase I inhibitor, irinotecan (in the U.S. trade name Camptosar) in those with metastatic pancreatic cancer.

In years 2007 through 2009, sixteen patients with advanced and locally-advanced gastroenteropancreatic neuroendocrine tumors were treated with the cisplatin plus irinotecan combination therapy. Several of these patients were then transitioned to long-acting release octreotide after disease control had been reached.  The median duration of progression-free survival was found to be 5.5 months.  And the median overall survival of the patients was 10.6 months.  The primary serious side-effect of this treatment regimen was hematological. The authors conclude that this combination is reasonably well tolerated, and moderately effective.

This study is encouraging, and needs further confirmation.  But it does improve our understanding as to potential treatment options for those with more advanced neuroendocrine tumors.

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Dale O’Brien, MD

Heavy-duty Multimodal Therapy with RFA for Locally Advanced Pancreatic Cancer

In some ways, both early stage and late stage pancreatic cancer (under current thinking paradigms) may be easier stages in which to offer standard care: early receives surgery (without or without neoadjuvant or adjuvant augmentation), and late stage is typically chemotherapy in one combination or another – at least initially involving either gemcitabine or 5-FU.  These approaches are of course always changing as challenges move the cutting edge of science and medicine forward.  The recent modest breakthrough on nab-paclitaxel (Abraxane) plus gemcitabine presented by Von Hoff et al. in San Francisco in January 2013 is perhaps a case in point.

But at least for now, it is often the middle presenting disease stages – locally advanced pancreatic cancer – that do not present easier logical choices. So it is with some interest that we find in the August issue of HPB, the official journal of the International Hepato Pancreato Biliary Association, that Pederzoli and colleagues from Casa di Cura Pederzoli, Peschiera del Garda of Italy have published an intriguing study reflecting the results of an aggressive treatment protocol for locally advanced adenocarcinoma of the pancreas.

The researchers did a retrospective study of the outcomes of multimodal treatment (“Triple Treatment”) on locally advanced pancreatic cancer with radiofrequency ablation (“RFA”), radiochemotherapy, together with systemic as well as intra-arterial chemotherapy. They reviewed the results of 168 consecutive patients who had been treated with initial OR subsequent RFA (from 2007 until 2011), discovering that the median survival of these groups was roughly the same at about 25 months.  This was in comparison to the group which had received the more specific and aggressive Triple Treatment modality regimen which carried a subsequent overall median survival duration of 34 months.

This research carries the inherent limitations of what appears to be a nested retrospective study, but represents an interesting hypothesis – maybe especially in this time of more aggressive combinations (such as FOLFIRINOX)  – and as such is highly deserving of further study.

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Dale O’Brien, MD

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