Systemic treatment of advanced pancreatic cancer

Pancreatic cancer belongs to the most malignant gastrointestinal cancers and, in its advanced stage, remains a deadly disease for nearly all affected patients. Treatment of metastatic adenocarcinoma of the pancreas not only involves chemotherapy and targeted therapy, but also requires attention to accompanying comorbidities as well as frequently intensive supportive treatment and psychosocial support. Gemcitabine-based combinations with fluoropyrimidines and platin analogs have essentially failed to provide a substantial prolongation of survival and may constitute a treatment option only in patients with a good performance status. Among targeted therapies, only the EGFR tyrosine kinase inhibitor erlotinib has shown activity which is marginal in the overall population, but clinically relevant in patients developing skin rash. New avenues of polychemotherapy are presently explored since the gemcitabine-free FOLFIRINOX-regimen (infusional 5-fluorouracil/folinic acid plus irinotecan and oxaliplatin) was shown to be markedly superior to gemcitabine in selected good-performance patients. Pancreatic cancer is notably characterized as a hypovascular tumor rich in desmoplastic stromal tissue. An innovative approach to treatment therefore focuses on peritumoral fibroblasts and aims to induce a depletion of the stroma either by inhibition of the hedgehog pathway or by targeting SPARC (secreted protein acidic and rich in cysteine) via application of albumin-bound paclitaxel.