Options and limitations of ductal pancreatic cancer treatment.
Ductal pancreatic cancer has still a dismal prognosis. Late diagnosis due to missing or unspecific early symptoms, early metastases and a relative resistance to radio- and chemotherapy characterize this tumor. There is only a chance of cure when a RO resection of the tumor is achieved.
Neoadjuvant treatment is as yet not an established treatment modality for pancreatic cancer. There are several smaller trials using chemotherapy or radiochemotherapy as neoadjuvant treatment strategies. Their results need confirmation in larger randomized trials. In the postoperative adjuvant or additive setting (after Rl resection) the ESPAC-trials und the CONKO-001 trial have established chemotherapy as treatment of choice. Gemcitabine is the preferred drug for the adjuvant treatment due to the more favourable toxicity profile compared to bolus 5-FU. Adjuvant chemotherapy with gemcitabine (or 5-FU) increases the 5-year overall survival rate from 9% to 20%.
In the palliative setting chemotherapy can prolong survival and improve symptoms such as pain and weight loss. Here, gemcitabine is still the standard of care. Gemcitabine can be combined with the small molecule Erlotinib, an EGFR receptor tyrosine kinase inhibitor, that has been shown to prolong overall survival in combination with gemcitabine if patients develop a marked skin rash during the first weeks of treatment with the drug. Other "targeted therapies" such as matrix metalloprotease inhibitors, inhibitors of angiogenesis, anti-EGFR antibodies or farnesyltransferasein-hibitors failed in large phase III trials. Novel compounds such as inhibitors of the sonic hedgehog or the Notch pathway are under clinical investigation.
Recently, data from a French group demonstrated that with intensified chemotherapy using a combination of 5-FU, irinote-can and oxaliplatin (the so called FOLFIRINOX protocol; Conroy ef a/., NEJM 2011, 364; 19:1817) a median overall survival in the metastatic situation of more than 11 months can be achieved. The corresponding figure for gemcitabine is merely 6.2 months. However, this combination regimen has substantially more toxicity compared to gemcitabine, in particular hematological and gastrointestinal toxicity.
Conclusion: The FOLFIRINOX data show that it is possible to treat pancreatic cancer more effectively. Future strategies should aim at using those regimens to achieve more RO surgical resections as the only curative treatment for pancreatic cancer.
Keywords: Pancreatic cancer; Targeted therapies; Adjuvant treatment; Palliative treatment
Thomas Seufferlein *
Department of Internal Medicine I, University Hospital Martin-Luther-University, Ernst-Grube-Strasse 40, D-06120 Halle (Saale), Germany
* Tel.: +49 345 557 2661; fax: +49 345 557 2053. E-mail address: email@example.com.
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|Publication:||Phytomedicine: International Journal of Phytotherapy & Phytopharmacology|
|Date:||Oct 15, 2011|
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