Pancreatic cancer is disease in which cancerous cells form in the tissue of the pancreas, a gland located behind the stomach and in front of the spine. Pancreatic adenocarcinoma is the most common type of pancreatic cancer. Pancreatic adenocarcinoma develops when exocrine cells in the pancreas begin to grow out of control.1

Pancreatic neuroendocrine tumors are less common and develop with endocrine cells in the pancreas. When diagnosed with pancreatic cancer, it is very important to know which type of cancer it is, exocrine or endocrine, because they are treated differently.1

Risk Factors
Risk factors are anything that can increase the likelihood of cancer from developing. Some risk factors are tobacco smoke, heavy alcohol use, high body mass index (BMI), genetics, pre-diabetes, long-term diabetes, family history of pancreatic cancer, contact with chemicals and heavy metals. Genes for cancer can be inherited from parent to child from a mutation in the genetic code but it does not necessarily mean they will develop cancer.1

Symptoms
There are no specific early warning symptoms of pancreatic cancer. Some possible symptoms that may occur include weight loss, nausea, vomiting, jaundice, new onset diabetes, trouble controlling diabetes, pain in the abdomen and back, and indigestion.

Having these symptoms can be a sign of pancreatic cancer, but other health conditions can cause them too. It is important to let your health care provide know if anything changes with your health.1

Treatment for Advanced Pancreatic Cancer
Erlotinib (Tarceva), an epidermal growth factor receptor (EGFR) inhibitor, is used to prevent cell replication by targeting the EGFR protein on cancer cells. Erlotinib is a systemic treatment and is used as targeted therapy.

Targeted therapy are drugs that target unique features on the cancer cells to make them more specific. Erlotinib taken with gemcitabine was approved by the FDA for locally advanced, inoperable, or metastatic pancreatic cancer in 2005.2

Mechanism of Action
Erlotinib is a tyrosine kinase inhibitor that inhibits the epidermal growth factor receptor on cells in the body. When erlotinib inhibits the EGFR receptor, the cell is no longer able to proliferate and will die. Since EGFRs are expressed on both normal and cancer cells, erlotinib can affect both.3

Indication
Erlotinib is a first-line treatment taken with gemcitabine for advanced pancreatic cancer that cannot be surgically removed and has not received chemotherapy before.6

Dosing Administration
The recommended dose of erlotinib taken with gemcitabine for advanced pancreatic cancer is 100 mg per day. The duration that erlotinib should be taken is until there is disease progression or intolerable toxicities.6

Clinical Studies
The National Cancer Institute of Canada Clinical Trials Group performed a phase 3 trial to compare the survival rate between gemcitabine alone and gemcitabine in combination with erlotinib. Gemcitabine, a chemotherapy drug, was used alone to treat pancreatic cancer when it was first introduced but there was no increase in survival.

The experiment was a phase 3 double-blind, randomized, placebo-controlled, international trial. There were 569 patients randomly assigned to the gemcitabine plus erlotinib or the gemcitabine plus placebo groups. Overall survival (OS) was significantly increased in the gemcitabine/erlotinib group compared with the gemcitabine/placebo group [HR 0.82; 95% CI, 0.69 to 0.99; P = .038].

The 1-year survival was also longer in the gemcitabine/erlotinib group, with a 23% increase compared with 17% in the gemcitabine/placebo group. Although, there was in increase in adverse events (AEs), they were not severe. Based on the phase 3 trial, gemcitabine combined with erlotinib significantly improved survival in patients with advanced pancreatic cancer.4,5

Contraindications
There are no contraindications per the manufacturer’s US labeling.6

Warning and Precautions
Renal and Hepatic Impairment
If a patient experiences renal or hepatic toxicity during treatment, the patient should withhold treatment until toxicity returns to normal levels. Once toxicity has resolved, treatment should be resumed with a 50 mg dose reduction.3

Interstitial Lung Disease
Erlotinib should be stopped if acute onset of pulmonary symptoms, such as shortness of breath, cough, and/or fever occurs.6

AEs
Cardiovascular events have been reported in patients taking gemcitabine plus erlotinib. Gastrointestinal AEs have been reported with symptoms of nausea, diarrhea, abdominal pain, and weight loss. Patients taking erlotinib may have increased susceptibility to infections.3

Drug Interactions
According to the manufacturer, the recommended administration is on an empty stomach (>1 hour before or 2 hours after eating food).Avoid taking with PPIs or H2 antagonists (H2RAs), if possible, and separate antacids by several hours. Taking PPIs or H2RAs can decrease the serum concentration of erlotinib.6

Dietary considerations are to avoid grapefruit and grapefruit juice because they can increase serum concentrations of erlotinib.3

Special Populations
Geriatrics
During clinical trials, there were no differences between older and younger adults in OS benefit. No dose adjustments are necessary for geriatrics.3

Pregnancy
Erlotinib is known to cross the placenta, which may cause fetal harm. Female patients should use effective contraception during and 1 month after treatment. There is not enough information to determine whether erlotinib is excreted in breast milk, so lactating women should not breastfeed during treatment and up to 2 weeks after final dose.3

Smokers
People who smoke have lower serum concentration levels. Patients should be advised to stop smoking before starting treatment. Smokers who took 300 mg per day had the same steady-state concentration as a non-smoker who received 150 mg per day.3

Storage/Stability
Erlotinib should be stored at 25°C (77°F). An oral suspension can be made using erlotinib tablets and Ora-Plus: Ora-Sweet, and will remain stable for at least 28 days at room temperature.3

References
1. American Cancer Society. What is pancreatic cancer? 2019 February 11 [cited 2020 June 2]. Available from: https://www.cancer.org/cancer/pancreatic-cancer/about/what-is-pancreatic-cancer.html

2. Cancer Connect. FDA approves Tarceva® in combination with Gemzar® for pancreatic cancer.  2018 June 1 [cited 2020 June 2]. Available from: https://news.cancerconnect.com/pancreatic-cancer/

3. Erlotinib (Lexi Drugs). Husdon (OH): Lexi-Comp; 1978-2020 [cited 2020 May 31]. Available from: http://online.lexi.com with subscription.

4. Kelley RK, and Ko AH. Erlotinib in the treatment of advanced pancreatic cancer. Biologics. 2008 March [cited 2020 June 1]; 2(1): 83–95. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727779/

5. Malcolm MJ, Goldstein D, Hamm J, Figer A, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A Phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 April [cited 2020 June 1]; 25(15): 1960. Available from: https://pubmed.ncbi.nlm.nih.gov/17452677/

6. Tarceva® [package insert]. South San Francisco, CA: Genentech USA, Inc; 2010. Accessed by: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021743s14s16lbl.pdf

About the Authors
Greg Watanabe
is a PharmD candidate at Pacific University’s School of Pharmacy, anticipated to graduate in spring 2021.
Jonathan Ogurchak, PharmD, CSP, is the founder and CEO of STACK, a pharmacy compliance management software, and serves as preceptor for a virtual Advanced Pharmacy Practice Experiential Rotation for specialty pharmacy, during which this article was composed.