Pancreatic Cancer: Drug Therapy

Therapeutic targets

• Improvement of the symptomatology
• Reduction of tumor mass
• Palliative (palliative treatment)

Therapy recommendations

• The most important therapeutic procedure is surgery (see “Surgical therapy” below).
• In pancreatic cancer, chemotherapy may be necessary in addition to surgical therapy, depending on the stage of the disease. A distinction can be made between neoadjuvant chemotherapy (i.e., chemotherapy before surgery) and adjuvant (“supportive”) chemotherapy.
  • Neoadjuvant chemotherapy (NACT) is recommended according to the current American Society of Clinical Oncology (ASCO) guidelines:
    • Reduced general condition that does not allow surgery at the time of diagnosis; however, this must be reversible in principle
    • radiological evidence for
      • Extrapancreatic tumor spread (outside the pancreas).
      • Arterial vascular infiltration
    • Very high CA19-9 levels, i.e., suspected disseminated disease.
  • Adjuvant chemotherapy is given to all patients in UICC(Union internationale contre le cancer) stage I-III after R0 (complete surgical removal of a tumor) or also R1 resection (macroscopically, the tumor was removed; however, in histopathology, smaller tumor parts are detectable in the resection margin) (according to the current S3- guideline for stage I-III+ R0 resection (removal of the tumor in healthy tissue; in histopathology, no tumor tissue is detectable in the resection margin)). This should be performed within eight weeks of resection unless contraindications exist. Contraindications include:
    • General condition worse than ECOG-PS (Eastern Cooperative Oncology Group-Performancestatus) 2.
    • Liver cirrhosis (“shrunken liver”) with Child-Pugh stage B or C.
    • Heart failure (cardiac insufficiency; NYHA stage III or IV).
    • Severe coronary artery disease (CAD; coronary artery disease).
    • Preterminal and terminal renal insufficiency (renal failure).
• In locally advanced unresectable tumor, palliative chemotherapy should be given. Here, the tyrosine kinase inhibitor erlotinib is used in combination with the standard chemotherapeutic agent gemcitabine for first-line therapy.
• A treatment regimen of chemotherapy and radiation chemotherapy can be performed in locally advanced inoperable tumor.
• Palliative radiotherapy should be performed only in symptomatic metastases.
• In advanced stages, palliative therapy (palliative treatment) is given:
  • Enteral nutrition, e.g., feeding via a PEG (percutaneous endoscopic gastrostomy: endoscopically created artificial access from the outside through the abdominal wall into the stomach).
  • Infusion therapy via a port catheter (port; permanent access to venous or arterial blood circulation).
  • Supplementation (“complementary therapy”) of pancreatic enzymes (2,000 IU per one gram of fat), insulin, and micronutrients (see under “Further therapy/nutritional medicine”)
  • Pain therapy (according to WHO stage scheme; see below “Chronic pain“).
• See also under “Further therapy”, esp. nutritional medicine.

Active substances (main indication)

Cytostatics

• For pancreatic cancer with R0 resection, adjuvant chemotherapy of gemcitabine or 5-FU/folinic acid (Mayo protocol) should be given for six months to prolong the recurrence-free interval. Therapy should begin no later than 6 weeks after surgery.
• For R1 resection, chemotherapy should be given with gemcitabine or 5-FU/folinic acid for six months.
• In patients who received adjuvant chemotherapy with gemcitabine and capecitabine, the prodrug of 5-fluorouracil, after resection of pancreatic ductal adenocarcinoma (R0 or R1 resection), the additional administration of capecitabine resulted in a prolongation of life from 25.5 to 28.0 months.
• In metastatic pancreatic cancer, options are available for first-line therapy:
  • Gemcitabine as monotherapy
  • Gemcitabine plus erlotinib (EGF receptor tyrosine kinase inhibitor).
  • Gemcitabine plus nab-paclitaxel (nanoparticle albumin bound paclitaxel) and folfirinox (5-fluorouracil [5-FU], folinic acid, oxaliplatin, irinotecan) → significant improvement in overall survival.

Additional notes

• After R0 or R1 resection, adjuvant chemotherapy with folfirinox significantly prolonged disease-free and overall survival in patients: after 3 years, overall survival was 63.4% in the folfirinox group and 48.6% in the gemcitabine group.

No information on dosages is provided here because changes in the respective regimens are common with cytostatic drugs