Mechanisms of Action and Administration Sequence of Common Antitumor Drugs

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Mechanisms of Action and Administration Sequence of Common Antitumor Drugs

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Mechanisms of Action and Administration Sequence of Common Antitumor Drugs.

In order to enhance the effectiveness of cancer treatment, a common approach involves using combination therapy with antitumor drugs, typically consisting of two or more agents.

The primary objective is to target different phases of the cell cycle or different cellular pathways in tumor cells with various drugs, thereby increasing treatment efficacy.

Proper and well-timed drug administration can lead to synergistic effects, not only improving therapeutic outcomes but also reducing or preventing toxicity and delaying the development of drug resistance.

This article provides a detailed overview of the administration sequences for commonly used antitumor drugs, including their mechanisms of action, common adverse reactions, administration timing, and intervals. Let’s delve into this information.

Mechanisms of Chemotherapy, Targeted Therapy, and Immunotherapy

1. Cell Cycle – Chemotherapy Drugs

Chemotherapy drugs act on various phases of the cell cycle to inhibit or kill cancer cells. Cell proliferation kinetics quantitatively study processes such as cell proliferation, differentiation, migration, cell death, and the influence of both internal and external factors on these processes. Depending on their targets in the cell cycle, antitumor drugs are categorized as:

• Cell Cycle Specific Agents (CCSA): Anti-metabolites, plant-derived antitumor drugs, and their derivatives.
• Cell Cycle Non-Specific Agents (CCNSA): Alkylating agents, antitumor antibiotics, and other antitumor drugs.

(Image Source: Reference 1)

2. Targeted Drugs

There are various types of targeted drugs, such as trastuzumab and pertuzumab targeting HER-2, lapatinib, neratinib, and small molecule tyrosine kinase inhibitors like pyrotinib. Trastuzumab and pertuzumab belong to large molecular monoclonal antibodies, primarily acting on extracellular domains. Pyrotinib and neratinib fall under small molecule tyrosine kinase inhibitors, acting on intracellular domains. Currently, ADC drugs like TDM-1, acting on extracellular domains, are highly effective by influencing downstream signaling of the EGFR family, especially the PI3K/Akt and MAPK pathways, inhibiting cancer cell proliferation, survival, migration, angiogenesis, drug resistance, and promoting apoptosis.

(Image Source: Reference 2)

3. Immune Checkpoint Inhibitors

Activation of T cells relies on dual signals. The first signal involves the binding of the Major Histocompatibility Complex (MHC)-presented antigens to the T-cell receptor (TCR). The second signal comprises co-stimulatory and co-inhibitory signals. PD-1 on T cells interacting with PD-L1 on tumor cells or antigen-presenting cells (APCs) effectively inhibits T cell activation, even leading to T cell apoptosis, reducing cytokine production, T cell lysis, and inducing antigen tolerance, allowing tumors to escape immune surveillance. PD-1/PD-L1 inhibitors block the interaction between PD-1 and PD-L1, restoring the recognition and cytotoxicity of immune cells, preventing tumor immune evasion.

(Image Source: Reference 3)

Factors Influencing the Administration Sequence of Antitumor Drugs

The administration sequence of antitumor drugs is typically influenced by factors such as drug interactions, cell proliferation kinetics, and drug irritability. Refer to Table 1 for specific administration sequences.

• Principles of Drug Interactions: Consider administration sequence based on pharmacokinetics and pharmacodynamics to maximize therapeutic synergy and sensitivity, while minimizing or avoiding increased side effects.

• Principles of Cell Proliferation Kinetics: Slow-growing solid tumors are treated first with cell cycle non-specific drugs followed by cell cycle-specific drugs, while faster-growing tumors follow the reverse order. Common cell cycle non-specific drugs include alkylating agents, platinum compounds, and antitumor antibiotics, whereas cell cycle-specific drugs affect nucleic acid biosynthesis and interfere with mitosis.

• Principles of Drug Irritability: When using two or more injectable antitumor drugs, it is advisable to administer the more irritative drug first, followed by the less irritative one. Foaming agents are typically administered first, and after the use of highly irritative drugs, flushing with normal saline or 5% glucose injection is recommended to reduce vascular irritation. At the beginning of chemotherapy, the vein structure is stable, and the chance of drug leakage is lower, minimizing adverse irritation to surrounding tissues.

Mechanisms of Action and Administration Sequence of Common Antitumor Drugs

References:

1. Matthews HK, Bertoli C, de Bruin RAM. Cell cycle control in cancer. Nat Rev Mol Cell Biol, 2022, 1: 74-88.
2. Xuhong JC, Qi XW, Zhang Y, et al. Mechanism, safety, and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib, and pyrotinib in HER2-positive breast cancer. Am J Cancer Res, 2019, 10: 2103-2119.
3. Tang Q, Chen Y, Li X, et al. The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers. Front Immunol, 2022, 9: 964442.
4. Expert Guidance on Intravenous Drug Safety Administration. Today’s Pharmacy, 1-23, 2023.
5. Drug Package Inserts.
6. Clinical Application Guidelines for Novel Antitumor Drugs (2022 Edition).

(source:internet, reference only)

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