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PANCREATIC CANCER
Pancreatic cancer is malignancy arising from the pancreas.
It is the 13th most common cancer in the world, 10th most common in the United States, and 4th leading cause of cancer-related deaths in the United Stated and Europe.
Exocrine tumors account for 95% of malignant pancreatic disease.
It is more common in women.
The median age of occurrence is at 71 years old.

Principles of Therapy

  • Patients previously given neoadjuvant therapy may receive adjuvant therapy after surgery for additional chemotherapy
    • Choice for adjuvant therapy should be based on the neoadjuvant therapy
    • Patients may be eligible for adjuvant therapy after neoadjuvant therapy given that complete recovery is seen

Neoadjuvant Therapy

  • Considered for pancreatic cancer patients w/ resectable & borderline resectable tumors
  • Improves overall survival of patients
    • Studies show decrease in tumor size prior to surgery
    • Improves tumor condition from borderline resectable to resectable status
    • Studies have shown a decrease in fistula-related morbidity rates after neoadjuvant treatment
  • May be done w/ chemotherapy alone or w/ radiation therapy
  • Helps categorize patients who are responsive to therapy
  • Has shown potential for treatment of early stages of micrometastases
  • Recommended for patients w/ biopsy-confirmed resectable pancreatic cancer w/ poor prognostic features
  • Further studies are needed to prove the efficacy of neoadjuvant therapy in patients w/ borderline resectable pancreatic cancer
    • If available, clinical trial participation is recommended; however, if not included in a clinical trial, patient w/ borderline resectable lesion can be given chemotherapy followed by chemoradiation then surgery

Pharmacotherapy

Recommended chemotherapeutic regimens

  • 5-FU + Cisplatin w/ concurrent radiation
  • Capecitabine w/ concurrent radiation
  • Continuous infusion 5-FU w/ concurrent radiation
  • FOLFIRINOX (preferred)
  • Gemcitabine + Cisplatin induction
  • Gemcitabine + Nab-Paclitaxel (preferred)
  • Gemcitabine induction followed by continuous infusion 5-FU/Capecitabine/Gemcitabine-based chemoradiation
  • GTX regimen

Gemcitabine

  • Administration of neoadjuvant treatment w/ Gemcitabine may help reduce the size & margin of the tumor in patients w/ resectable PC
  • Although some studies have shown that when given concurrently w/ radiation, patients w/ resectable PC showed worsening of the disease, leading to the need for restaging & cancellation of surgery

FOLFIRINOX

  • Further studies are needed to prove the efficacy & safety of FOLFIRINOX before Capecitabine-based chemoradiation & surgery in patients w/ borderline resectable PC

Adjuvant Therapy

  • Chemoradiotherapy is preferred as compared to R1 surgical resection for tumors w/ high possibility for locoregional recurrence & metastasis
  • Before starting adjuvant chemotherapy, perform a full restaging scan to exclude metastatic disease
  • Gemcitabine is preferred over 5-FU because of its better toxicity profile
  • FOLFIRINOX or Gemcitabine + Nab-Paclitaxel is an alternative for patients w/ good performance status who relapsed after adjuvant therapy (depends on length of time from finishing adjuvant therapy)

For patients w/ locally resectable tumors

  • Chemotherapy may be given alone or in combination w/ radiation therapy
  • 5-FU is most commonly given w/ Leucovorin
  • Chemoradiation therapeutic regimens include:
    • 5-FU + Cisplatin w/ concurrent radiation
    • 5-FU + Leucovorin (preferred)
    • Capecitabine (monotherapy)
    • Capecitabine w/ concurrent radiation
    • Continuous infusion 5-FU
    • Continuous infusion 5-FU w/ concurrent radiation
    • Gemcitabine (monotherapy) (preferred)
    • Gemcitabine w/ concurrent radiation

For patients w/ borderline resectable tumors

  • Preoperative therapy w/ chemoradiation/induction chemotherapy followed by chemoradiation may increase the rate of R0 resections
  • Chemotherapy may be given alone or in combination w/ radiation therapy
  • Chemotherapeutic regimens include:
    • 5-FU + Cisplatin w/ concurrent radiation
    • Capecitabine (monotherapy)
    • Capecitabine w/ concurrent radiation
    • Continuous infusion 5-FU
    • Continuous infusion 5-FU w/ concurrent radiation
    • FOLFIRINOX (preferred)
    • Gemcitabine (monotherapy) (preferred)
    • Gemcitabine followed by continuous infusion 5-FU/Capecitabine/Gemcitabine-based chemoradiation
    • Gemcitabine w/ concurrent radiation
    • GTX regimen

For patients w/ locally advanced, unresectable & metastatic tumors

  • Treatment depends on performance status of the patient
    • Patients w/ good performance status & Eastern Cooperative Oncology Group (ECOG) score of 0-2 may undergo chemotherapy & CRT
  • If available, clinical trial participation is recommended
  • Chemotherapeutic regimens of unresectable/locally advanced tumors include:
    • 5-FU (monotherapy)
    • 5-FU + Cisplatin w/ concurrent radiation
    • Capecitabine (monotherapy)
    • Capecitabine w/ concurrent radiation
    • Continuous infusion 5-FU w/ concurrent radiation
    • Fluoropyrimidine + Oxaliplatin (including FOLFOX [Continuous infusion 5-FU , Leucovorin, Oxaliplatin] & CapeOx [Capecitabine + Oxaliplatin]
    • FOLFIRINOX (preferred)
    • Gemcitabine (monotherapy) (preferred)
    • Gemcitabine induction
    • Gemcitabine + Capecitabine
    • Gemcitabine + Cisplatin
    • Gemcitabine + Cisplatin induction
    • Gemcitabine + Nab-Paclitaxel (preferred)
    • Gemcitabine + Erlotinib (preferred)
    • GTX regimen
  • Chemotherapeutic regimens of metastatic tumors include:
    • Capecitabine (monotherapy)
    • Capecitabine + Oxaliplatin
    • Continuous infusion 5-FU
    • FOLFIRINOX (preferred)
    • FOLFOX
    • Gemcitabine (monotherapy)
    • Gemcitabine + Capecitabine
    • Gemcitabine + Cisplatin
    • Gemcitabine + Nab-Paclitaxel (preferred)
    • Gemcitabine + Erlotinib
    • GTX regimen
    • TS-1 (Tegafur, Gimeracil & Oteracil)

5-FU

  • Recommended as first-line treatment option for patients w/ locally advanced unresectable & metastatic pancreatic caner
  • Combination w/ Cisplatin may be considered in patients w/ BRCA1/BRCA2-related pancreatic cancer

Capecitabine

  • Recommended option for patients w/ locally advanced unresectable & metastatic pancreatic cancer
    • Second-line treatment option for patients w/ locally advanced unresectable & metastatic pancreatic cancer after Gemcitabine-based 1st-line treatment
  • Showed significant improvement in overall survival in patients w/ advanced pancreatic cancer

Capecitabine + Continuous Infusion 5-FU

  • Recommended as first-line treatment option for patients w/ locally advanced unresectable & metastatic pancreatic cancer

Capecitabine + Oxaliplatin (CapeOx)

  • Second-line treatment option for patients w/ locally advanced unresectable & metastatic pancreatic cancer after Gemcitabine-based first-line treatment

Fluoropyrimidine (5-FU + Leucovorin or Capecitabine) + Oxaliplatin

  • Includes CapeOx (Capecitabine + Oxaliplatin) & modified FOLFOX
  • Second-line treatment option for patients w/ locally advanced unresectable & metastatic pancreatic cancer after Gemcitabine-based first-line treatment
  • Modified FOLFOX may extend the overall survival in patients w/ advanced Gemcitabine-refractory pancreatic cancer

FOLFIRINOX

  • Recommended as first-line therapy for patients w/ locally advanced unresectable & metastatic pancreatic cancer
  • May be considered in patients w/ ECOG performance status 0-1 w/ bilirubin level <1.5 x ULN
  • May be used in patients w/ BRCA1/BRCA2-related pancreatic cancer & pancreatic acinar cell carcinoma
  • Several studies show that this combination has anti-tumor activity & promising response rates in patients w/ locally advanced unresectable disease, anti-tumor activity, >30% response rate, & dramatic improvements in median progression-free survival & objective response rates in patients w/ metastatic pancreatic cancer

Gemcitabine

  • Monotherapy is recommended as an option for symptomatic patients w/ locally advanced & metastatic unresectable pancreatic cancer w/ poor performance status
  • Studies show that there was an increase in the median survival rate w/ fixed-dose rate regimen compared w/ monotherapy
  • Second-line treatment option for patients w/ locally advanced unresectable & metastatic pancreatic cancer after 5-FU-based 1st-line treatment
  • May be considered in patients w/ ECOG performance status 2 &/or bilirubin level >1.5 x ULN

Gemcitabine + Nab-Paclitaxel

  • Recommended for the treatment of pancreatic cancer patients w/ advanced disease & good performance status
  • May be considered in patients w/ ECOG performance status 2 due to heavy tumor load & in patients w/ ECOG performance status 0-1 w/ bilirubin level <1.5 x ULN
  • Studies have shown that addition of albumin-bound Paclitaxel to Gemcitabine significantly improved overall survival, response rate, & progression-free survival rates, w/ up to 42 mth long-term overall survival reported

Gemcitabine + Erlotinib

  • Recommended option for patients w/ locally advanced unresectable & metastatic pancreatic cancer w/ good performance status
  • Significant improvement in overall survival & progression-free survival were seen in patients w/ advanced pancreatic cancer who received this combination

Gemcitabine + Capecitabine

  • Considered as a treatment option for pancreatic cancer patients w/ locally advanced metastatic disease w/ good performance status who are willing to undergo more aggressive treatment regimens

Gemcitabine + Cisplatin

  • Recommended option for patients w/ strong hereditary factors as the origin of the disease

GTX regimen

  • Recommended option for patients w/ advanced pancreatic cancer & good performance status
  • May improve overall response rate
  • Adverse effects include leukopenia, grade 3/4 anemia & thrombocytopenia

Modified FOLFOX

  • Second-line treatment option for patients w/ locally advanced unresectable & metastatic pancreatic cancer after Gemcitabine-based first-line treatment

TS-1 (Tegafur-Gimeracil-Oteracil)

  • A reasonable alternative following postsurgical resection for metastatic pancreatic adenocarcinoma
  • A combination that reduced the GI adverse effects of 5-FU
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