Pancreatic cancer medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]

Overview[edit | edit source]

In patients with pancreatic cancer, surgery is the primary modality of treatment. However, surgery is performed only in a small fraction of patients who have resectable lesions. Majority of patients have unresectable disease and are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy. Curative resection is not performed in cases of extrapancreatic involvement that require palliative therapy. As per the guidelines of The National Comprehensive Cancer Network (NCCN), patients with locally advanced unresectable or metastatic disease should be treated with a combination of Leucovorin, 5-fuorouracil, Oxaliplatin, and Irinotecan also known as FOLFIRINOX regimen. Neoadjuvant therapy is preferred as shrinkage of the tumor using chemotherapy makes resection easier and improves patient prognosis. Radiotherapy may also form part of neoadjuvant therapy to facilitate tumor shrinkage, but its use on unresectable tumors remains controversial.

Medical Therapy[edit | edit source]

• In patients with pancreatic cancer, surgery is the primary modality of treatment.
• Patients with unresectable disease are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy.
• Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.
• The different types of treatment modalities available for patients with pancreatic cancer are:
  • Surgery
  • Radiation therapy
  • Chemotherapy
  • Chemoradiation therapy
  • Targeted therapy

• New types of treatment such as biologic therapy, are being studied in clinical trials.

Chemotherapy guidelines[edit | edit source]

• The National Comprehensive Cancer Network (NCCN) has recommended guidelines for treatment in patients based on their performance status.
• In order to predict survival of patients in various stages of pancreatic cancer, the performance status of a patient is a major prognostic factor.
• Patients with poor prognostic factors have poor performance status. This includes:^[1]
  • Metastatic disease
  • Large tumor
  • Severe weight loss
  • Preferred regimens based on performance status in locally advanced/metastatic disease are enlisted in the table as follows:^{[2][3][4][5][6][7][8][9][10][11][12][13][14]}

Preferred regimens based on the stage of pancreatic cancer:[edit | edit source]

Stages I-II:

Neoadjuvant therapy :

• There are no standard regimens currently for neoadjuvant treatment of resectable pancreatic cancer.
• Preferred neoadjuvant drug regimens are as follows:
  • Capecitabine
  • Fluorouracil
  • Fluorouracil or Cisplatin plus radiation
  • Gemcitabine or Gemcitabine or Cisplatin

Adjuvant chemotherapy:

• In patients with resectable pancreatic cancer:
• Preferred regimen: Gemcitabine 1000 mg/m ² IV q30min for 3 weeks; every 4 weeks for six cycles

Adjuvant chemotherapy and chemoradiation:

Preferred regimen (1): Gemcitabine 1000 mg/m ² IV q30min weekly for 3 weeks

Preferred regimen (2): 5-fluorouracil (FU) 250 mg/m ²/day continuous IV infusion via pump

Preferred regimen (3): Radiotherapy 1.8 Gy/day upto a total of 50.4 Gy; then  3-5 wk after chemoradiation: Gemcitabine 1000 mg/m ² IV q30 min weekly; every 4 weeks for three cycles

Stage III:[edit | edit source]

Neoadjuvant therapy:

Preferred regimen (1): Gemcitabine 1000 mg/m ² IV q30 min weekly for 3 weeks, every 4 weeks

Preferred regimen (2): 5-fluorouracil (FU) 500 mg/m ²/day IV bolus on days 1-3 and 29-31 with radiotherapy, 40 Gy

Stage IV:

• Preferred regimen (1): Protein bound Paclitaxel 125 mg/m ² AND Gemcitabine 1000 mg/m ² IV over 30-40 min on days 1, 8, and 15 q4weeks
• Preferred regimen (2): Gemcitabine 1000 mg/m ² IV over 30 min q1week for 7 wk, followed by 1 week off, then weekly for 3 wk
• Preferred regimen (3): Gemcitabine 1000 mg/m ² IV over 30 min on days 1 and 15 AND  Cisplatin 50 mg/m ² IV over 1 h on days 1 and 15, q4 weeks
• Preferred regimen (3): Gemcitabine 1000 mg/m ² IV weekly for 7 wk AND  Erlotinib 100 mg PO daily on days 1-56 then Gemcitabine 1000 mg/m ² IV on days 1, 8, and 15 plus  Erlotinib 100 mg PO q24h on days 1-28 in four cycles 
• Preferred regimen (4): Gemcitabine 1000 mg/m ² IV weekly for 3 weeks q4weeks AND  Capecitabine 1660 mg/m ²/day weekly for 3 wk; q4weeks
• Preferred regimen (5): Oxaliplatin 85 mg/m ² IV AND  Irinotecan 180 mg/m ² IV on day 1 AND  Leucovorin 400 mg/m ² IV on day 1, followed by 5-fluorouracil (FU) 400 mg/m ² IV bolus on day 1 and then 2400 mg/m ² IV infusion over 46 h on days 1 and 15

Alternative treatment recommendations for Stage IV:

• Alternative regimen (1): Capecitabine 1250 mg/m ² PO q12h for 2 weeks, every 3 weeks 
• Alternative regimen (2): Capecitabine 1000 mg/m ² PO q12h for 2 weeks; every 3 weeks AND Erlotinib 150 mg PO daily
• Alternative regimen (3): Irinotecan liposomal 70 mg/m ² IV infused over 1.5h AND  Leucovorin 400 mg/m ² IV infused over 30min ,followed by  5-fluorouracil (FU) 2400 mg/m ² IV infused over 46 h q3 weeks 
• Alternative regimen (4): 5-fluorouracil (FU) 2000 mg/m ² IV continuous on days 1, 8, 15, and 22 AND Leucovorin 200 mg/m ² IV over .5h on days 1, 8, 15, and 22 AND Oxaliplatin 85 mg/m ² IV on days 8 and 22; q42d

Comparison of one year survival of various regimens is depicted in the table below:

Radiation Therapy[edit | edit source]

• The role of radiotherapy as an auxiliary (adjuvant) treatment after potentially curative surgery is controversial.^[43][44][45]
• Radiotherapy may form part of neoadjuvant therapy to attempt to shrink a tumor to a resectable state, but its use on unresectable tumors remains controversial.^[19][46]

Palliative Therapy[edit | edit source]

Palliative therapy in patients with pancreatic cancer mainly involves the management of symptoms arising as a result of complications of therapy:^{[47][48][49][50][51][52]}

• Pain:
  • There are various techniques for pain management as palliative therapy in patients with advanced stage of pancreatic cancer:
    • Narcotic analgesics
    • Narcotic analgesics AND tricyclic antidepressants or antiemetics
    • Radiation therapy

Adjuvant and Neoadjuvant therapy[edit | edit source]

• The use of gemcitabine as adjuvant therapy is considered a standard form of therapy following surgical resection in pancreatic cancer patients.^{[39][44][53][54][55][56][57][58][59][60]}

• Neoadjuvant therapy may be used as a form of therapy due to the following reasons:^{[4][19][61][62][63][64][65][66][67][68]}
  • Toxic effects of chemotherapy can be tolerated more easily before surgery as compared to after resection.
  • Shrinkage of tumor with neoadjuvant therapy makes resection easier and improves patient prognosis.
  • Systemic treatment for cancer involving various systems improves prognosis.
• No therapy is considered as first line therapy under this category.
• Decisions for treatment are made on an individual basis.

New Treatments[edit | edit source]

• Irinotecan in an encapsulated form inside a nanoliposome is being used in advanced pancreatic cancer patients who have earlier been treated using gemcitabine-based chemotherapy.^[69]
• Liposomal Irinotecan is used along with leucovorin and fluorouracil.^[70]

References[edit | edit source]

Template:WikiDoc Sources