• 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

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