Pancreatic Disorders & Therapy
Open Access

Chemotherapeutic Drugs for Pancreatic Cancer: An Overview of Current Treatments and Advances

Fu Deliang^{* *}Correspondence: Fu Deliang, Department of Pancreatic Surgery, University of Fudan, Shanghai, China, Email:

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Description

Pancreatic cancer is one of the most challenging malignancies to treat, characterized by its aggressive nature and late-stage diagnosis. The prognosis for patients diagnosed with this disease remains poor, with a five-year survival rate of approximately 10%. However, advancements in medical science have led to the development of several chemotherapeutic agents that plays an important role in the management of pancreatic cancer. This article analyses the key chemotherapeutic drugs used in treating this condition, their mechanisms, efficacy, and emerging therapies. Pancreatic cancer often presents with nonspecific symptoms, making early detection difficult. The majority of cases are diagnosed at an advanced stage, which significantly complicates treatment. The most prevalent form of pancreatic cancer is Pancreatic Ductal Adenocarcinoma (PDAC), which represents approximately 90% of cases diagnosed. Standard treatment options include surgery, radiation, and chemotherapy, with chemotherapy being the cornerstone for unresectable or metastatic disease.

Standard chemotherapeutic regimens

Gemcitabine: Gemcitabine was one of the first chemotherapeutic agents to show efficacy against pancreatic cancer. It is a nucleoside analogue that disrupts DNA synthesis, ultimately inhibiting cell proliferation. Clinical studies have demonstrated that gemcitabine improves survival rates compared to supportive care alone. It is often administered as a single agent or combined with other drugs, such as nab-paclitaxel.

FOLFIRINOX: It is a combination chemotherapy regimen that includes four drugs Fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin. This regimen has shown significant survival benefits in patients with good performance status. Clinical trials have indicated that FOLFIRINOX can extend overall survival compared to gemcitabine alone, making it a preferred option for fit patients with advanced pancreatic cancer.

Nab-paclitaxel and gemcitabine: The combination of nab-paclitaxel (a nanoparticle formulation of paclitaxel) and gemcitabine has emerged as a standard treatment for metastatic pancreatic cancer. Nab-paclitaxel enhances the delivery of gemcitabine by altering the tumour microenvironment and improving drug penetration. Clinical studies have shown that this combination leads to improved overall survival and response rates compared to gemcitabine alone.

Emerging therapies and combinations

As the understanding of pancreatic cancer biology evolves, new therapeutic strategies are being explored to enhance treatment efficacy.

Targeted therapies: These therapies aim to disrupt specific molecular pathways that contribute to the growth and spread of cancer. For instance, the use of erlotinib, an Epidermal Growth Factor Receptor (EGFR) inhibitor, has been studied in combination with gemcitabine. While results have been mixed, ongoing research continues to explore the potential of combining targeted agents with traditional chemotherapy.

Immunotherapy: Immunotherapy is a potential area of research for pancreatic cancer, though it has faced challenges due to the tumour's immunosuppressive microenvironment. However, clinical trials are investigating combinations of immune checkpoint inhibitors with chemotherapy. These strategies aim to enhance the immune response against pancreatic tumours and improve patient outcomes.

PARP inhibitors: Drugs like olaparib, are being studied particularly in patients with BRCA1 or BRCA2 mutations. These agents exploit the concept of "synthetic lethality," where cancer cells with defective DNA repair pathways are selectively targeted. Initial studies indicate that combining PARP inhibitors with chemotherapy could lead to improved responses in genetically predisposed populations.

Side effects and management

Chemotherapeutic agents are associated with a range of side effects, which can significantly impact patients' quality of life. Frequent side effects include nausea, vomiting, fatigue, low white blood cell counts, and diarrhea. Management of these side effects is important for maintaining treatment adherence and overall patient wellbeing. Supportive care measures, such as antiemetic’s, growth factors, and dietary modifications, can help mitigate these effects.

Conclusion

Chemotherapeutic drugs are a critical component in the management of pancreatic cancer, particularly for patients with advanced disease. Regimens such as gemcitabine, FOLFIRINOX, and nab-paclitaxel combined with gemcitabine have improved survival outcomes and quality of life for many patients. As research continues to evolve, the integration of targeted therapies and immunotherapy offers hope for more effective treatments in the future.