Semlitsch, T. and Zengerer, A. and Jeitler, K. (2014): Nab-Paclitaxel (Abraxane®) as first-line therapy for metastatic adenocarcinoma of the pancreas. DSD: Horizon Scanning in Oncology 43.
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Pancreatic cancer is the fourth most common cause of cancer-related death in Western Europe and North America. In Austria 1,424 men and women died of pancreatic cancer in 2009, although it accounts for only 4% of all cancers diagnosed. This high lethality results from the fact that pancreatic cancer is usually diagnosed at advanced stages, since it does not cause early symptoms. Paclitaxel, a natural mitotic inhibitor, blocks the progression of mitosis and triggers apoptosis or reversion to the G-phase of the cell cycle without cell division.
In September 2013, the FDA authorised Abraxane®, the albumin-bound formulation of paclitaxel (nab-paclitaxel), in combination with gemcitabine for the first-line treatment of patients with metastatic pancreatic cancer. For Europe, approval was achieved in December 2013.
Publications reporting on one phase III trial and three phase II trials were identified, but to date results are only available for the phase III trial and two of three the phase II trials.
In the multicentre, open-label randomised controlled phase III trial (MPACT), nab-paclitaxel plus gemcitabine was compared to gemcitabine alone in 861 patients previously not treated for their metastatic disease. The study showed statistically significant improvements for the combination therapy regarding OS (8.5 vs. 6.7 months), PFS (5.5 vs. 3.7 months) and ORR (23 vs. 7%). However, more than 50% of the patients in the intervention group developed a peripheral neuropathy, with 17% of them being an AE of grade ≥ 3. In the control group this grade ≥ 3 AE occurred in only 1% of the patients. Other frequent AEs of grade ≥ 3 with nab-paclitaxel and gemcitabine were neutropenia, leukopenia and fatigue. Data on health-related quality of life were not available.
The regulatory approval of nab-paclitaxel in combination with gemcitabine means that a new therapy is available for metastatic pancreatic cancer, a disease for which therapeutic options are generally limited. This new treatment has demonstrated an increase in PFS and OS, but due to the study’s inclusion criteria it is eligible only for patients with a good performance status and a bilirubin level within the normal range. Apart from the benefits, nab-paclitaxel plus gemcitabine is associated with higher rates of AEs, especially a strongly increased rate of peripheral neuropathy.
To date, data on QoL are missing and there are no studies comparing nab-paclitaxel plus gemcitabine to FOLFIRINOX -the other combination chemotherapy recommended for patients with metastatic pancreas carcinoma- and good performance status. Therefore, many unresolved questions regarding this therapy still remain.
|Item Type:||DSD: Horizon Scanning in Oncology|
|Keywords:||Pancreatic cancer, pancreatic adenocarcinoma, Paclitaxel, Abraxane®|
|Subjects:||WI Digestive system > WI 800-830 Pancreas|
WB Practice of medicine > WB 300-962 Therapeutics
QZ Pathology > QZ 200-380 Neoplasms.Cysts
QV Pharmacology, toxicology, pharmacy > QV 60-370 Pharmacology
|Series Name:||DSD: Horizon Scanning in Oncology 43|
|Deposited on:||07 Mar 2014 14:35|
|Last Modified:||07 Mar 2014 14:35|
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