Pancreatic cancer medical therapy

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

Overview

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

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

Chemotherapy guidelines

  • 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]
PREFERRED REGIMENS BASED ON PERFORMANCE STATUS IN LOCALLY ADVANCED/METASTATIC DISEASE
Good perfomance status FOLFIRINOX[15][16][17][18][19][20][21][22][23]
Good perfomance status with intolerance to FOLFIRINOX Paclitaxel protein bound AND Gemcitabine
Poor performance status Gemcitabine monotherapy[24][25][26][27]
Poor performance status refractory to Gemcitabine Capecitabine OR capecitabine AND erlotinib[28]

Preferred regimens based on the stage of pancreatic cancer:

Stages I-II:

Neoadjuvant therapy :

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:

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:

ONE YEAR SURVIVAL OF DIFFERENT REGIMENS
One year survival of FOLFIRINOX (leucovorin AND 5-fluorouracil [LV5-FU] AND oxaliplatin AND Irinotecan) is better than Gemcitabine[16][29][30][31][32][33][34]
One year survival of Gemcitabine AND Erlotinib is better than Gemcitabine[13][35][36]
One year survival of Gemcitabine AND Capecitabine is better than or equal to Gemcitabine [2][37][38][39][40]
One year survival of Gemcitabine AND nanoparticle albumin-bound (nab)-Paclitaxel is better than Gemcitabine[41][42]

Radiation Therapy

Palliative Therapy

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]

Adjuvant and Neoadjuvant therapy

New Treatments

References

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