Pancreatic cancer

Methods of treatment

Treatment options for pancreatic cancer

Pancreatic cancer is treated depending on its stage, namely the spread of the tumor process in the body.

Resectable cancer — according to visual assessment, cancer has not spread beyond the pancreas and has not grown into nearby large blood vessels.

Depending on the location of the tumor tissue and to increase the effectiveness of treatment for an operable tumor, chemotherapy / chemoradiotherapy can be additionally used:

before surgery, to reduce the size of the tumor(neoadjuvant therapy)
after surgery, to prevent the spread of tumor cells that may have remained after surgery

Borderline resectable cancer involves damage to nearby blood vessels without sprouting and surrounding them.

Surgical removal is possible, used in combination with other methods.

Sometimes the decision on the initial tactics (possibility of carrying out / volume of the operation) changes during the surgery.

Depending on the specific situation, chemotherapy (mFOLFIRINOX, GEMCAP) / chemoradiotherapy is additionally used:

before surgery, to reduce the size of the tumor (neoadjuvant therapy)
after surgery, to prevent the spread of tumor cells that may have remained after surgery

Locally advanced (unresectable) cancer has grown too far into nearby blood vessels or other tissues to be completely removed by surgery, but has not spread to the liver or distant organs and tissues.

Surgical treatment does not increase life expectancy, it is used to relieve symptoms (blockage of the bile ducts, small intestine, organ compression).
Chemotherapy is the standard treatment (mFOLFIRINOX, GEMCAP).
Chemo-radiotherapy should assess the benefit-risk ratio due to side effects and lower tolerance.
Targeted therapy or immunotherapy may also be added to the treatment regimen in selected cases.

Metastatic (spread) cancer, as a rule, first spreads to the abdomen and liver. It can also metastasize to the lungs, bones, brain, and other organs.

Chemotherapy is the standard treatment (FOLFIRINOX, gemcitabine + paclitaxel, gemcitabine + platinum-based drugs, gemcitabine).
A germline or somatic mutation in BRCA or PALB2 genes determines the choice of gemcitabine + platinum-based drugs regimen. After at least 16 weeks of first-line platinum-based chemotherapy, it is recommended to consider either continuing chemotherapy (including supportive chemotherapy with fluoropyrimidines or FOLFIRI) or switching to therapy with olaparib until disease progression or intolerable toxicity.
If there are certain genetic alterations, immunotherapy or targeted therapy may be indicated.
Radiation therapy, nerve block, bile duct stenting may be used to relieve symptoms.

Treatment of advanced or recurrent pancreatic cancer

When pancreatic cancer recurs, it most often first appears in the liver, but may also spread to the lungs, bones, or other organs.

If patient’s health condition is satisfactory chemotherapy is prescribed. If chemotherapy took place earlier, and it inhibited the growth of the tumor for some time, then the same scheme can be chosen. Or some other chemotherapy protocols are prescribed, sometimes along with targeted therapy. Immunotherapy may also be given in some cases of recurrent pancreatic cancer. A patient can also find out about ongoing clinical trials.

Surgery

Surgical treatment offers the only real chance for a cure. The most commonly used method of surgical treatment of the pancreatic head of a malignant tumor is gastro-pancreatoduodenal resection. If the tumor is localized in the body or tail of the pancreas — distal pancreatectomy. Total pancreatectomy is required when the tumor process spreads throughout the pancreas or in the presence of several foci of cancer.

Radiation therapy

is indicated when

preoperative treatment, to reduce the size of the tumor
in locally advanced pancreatic cancer after surgical treatment in case of relapse,
growth of a primary unresectable tumor after chemotherapy in the absence of distant metastases,
to relieve severe pain in metastatic lesions or after surgery to reduce the risk of cancer recurrence.

This is usually external radiation for 5-6 weeks. Stereotactic radiation therapy provides targeted irradiation of the tumor in a small number of sessions.

Chemotherapy

It is prescribed after surgical removal of pancreatic cancer to prevent possible tumor recurrence. Currently gemcitabine (Gemzar)

It is one of the most commonly used drugs. It is used alone, with the drug paclitaxel (Abraxane), especially in debilitated patients and in the presence of comorbidities, or in combination with other drugs such as capecitabine (Xeloda) (GEMCAP).
According to the Russian clinical guidelines (Russco), the combination of gemcitabine and erlotinib is not recommended for patients with pancreatic cancer, as a randomized trial showed a minimal benefit in life expectancy with a significant increase in toxicity.
For patients with a mutation in the BRCA1, BRCA2, or PALB2 genes, a combination of gemcitabine with a platinum-based therapy (cisplatin, carboplatin, or oxaliplatin) is recommended.
In patients with metastatic prostate cancer (PC) and pathogenic germline mutations in the BRCA genes, in the absence of progression after at least 16 weeks of platinum-based first-line chemotherapy, it is recommended to consider either continuing chemotherapy or switching to maintenance therapy with olaparib until disease progression or intolerable toxicity.

Targeted Therapy

Erlotinib (Tarceva) is a drug that blocks the EGFR cell receptor. The American Society of Clinical Oncology recommends prescribing it with a combination of gemcitabine for metastatic pancreatic cancer. In certain cases, patients may benefit more from this combination than others.

Olaparib (Lynparza) is a PARP inhibitor. PARP enzymes are usually involved in a pathway that helps repair damaged DNA inside cells. BRCA genes are usually involved in a different DNA repair pathway, and mutations in one of these genes can block that pathway. Therefore, PARP inhibitors lead to the death of cells with a mutation in the BRCA1, BRCA2, or PALB2 genes. Olaparib can be used to treat advanced pancreatic cancer in people with a known or suspected BRCA1, BRCA2, or PALB2 gene mutation whose cancer has not gotten worse after at least 4 months of chemotherapy that includes platinum-based drugs (such as oxaliplatin or cisplatin).

NTRK inhibitors. About 1% of pancreatic cancers have alterations in one of the NTRK genes.

Larotrectinib (Vitraqui) and entrectinib (Rozlitrek) target proteins produced by the NTRK genes. These drugs can be used in people with advanced pancreatic cancer that has been found to have an NTRK gene alteration.

Immunotherapy may be indicated for high levels of microsatellite instability (MSI-H).