ABSTRACT
The interactions among drugs, tumor and host are critical for a response to therapy and for outcome. Anticancer herbs used in Chinese medicine are classified into 4 groups based on their target (tumor, patient and drug) as follows: eliminating pathogenic factors, strengthening the body resistance, enhancing effects of chemotherapy and detoxication of chemotherapy. Correspondingly, anticancer drugs used in Western medicine can be classified into 4 groups as follows: cytotoxic drugs, biological response modifiers, chemosensitizers and chemoprotectants.
Based on the theory of Chinese medicinal formulas, prescriptions are composed of four constituents, namely, primary constituent (main component of the formula prescription), minister constituent (second component of formula prescription), adjuvant constituent (adjuvant component of the formula prescription) and messenger constituent (component making the formula prescription targeting pathological tissues). To control the interaction among drugs and to modulate the interaction among the tumor, patient and drugs, we suggest that combined therapy for Western medicine might include 4 constituents, i.e., primary, cooperative, adjuvant and modulatory constituent. Cytotoxic drugs frequently are used as primary and cooperative constituents, whereas biological response modifiers and biochemical modulators are usually regarded respectively as adjuvant drugs and modulatory constituents.
We believe these new concepts may be helpful for the aim of appropriately designing, evaluating or providing combination therapy.
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Introduction
Herbs have been used as anticancer drugs for more than thousands of years. The activity of an herb can be altered by another herb, and such interaction can often be clinically significant. Compounded prescriptions are a feature of Traditional Chinese Medicine (TCM), which is the art of making use of the interaction of herbs to enhance the therapeutic effects and reduce side reactions.
Combined chemotherapy is a critical method of anticancer strategy in Western medicine to improve the therapeutic response and outcome. Multidrug Western regimens usually include different drugs that have the different pharmacological mechanisms and toxic reactions to increase efficacy and decrease toxicity. What inspiration can be drawn from a comparative study of anticancer therapy between TCM and Western medicine?
The classification of anticancer drugs based on targets
The interaction among the tumor, patient and drug plays a critical role in controling tumors. Functional interactions between the host and abnormal cells can be altered by the tumor cells at different stages of carcinogenesis[1]. This homeostasis between host and tumor cells also may be altered by anticancer drugs. Cytotoxic drugs not only suppress cancer tissue but, also have a suppressive effect on the immune system, whereas some non-cytotoxic drugs can modulate the interaction among tumor cells, host response and cytotoxic drugs.
Anticancer herbs can be classified into 4 groups based on their target (tumor, patient and drug) as follows: eliminating pathogenic factors, strengthening the body resistance, enhancing the effects of chemotherapy and detoxication of chemotherapy. Correspondingly, anticancer drugs in Western medicine can be classified into 4 groups based on their targets, i.e., cytotoxic drugs, biological response modifiers (BRMs), chemosensitizers and chemoprotectants. Cytotoxic drugs can eliminate tumor tissue, BRMs can regulate the host response of carcinogenesis, chemosensitizers can affect the metabolic pathway of cytotoxic drugs to enhance the chemosensitivity, and chemoprotectants can reduce the toxic side effects of cytotoxic drugs (Table 1).
Classification of anticancer drugs based on mechanism of activity.
The host response to the tumor has a two-edged effect on carcinogenesis-suppression and promotion. On one hand, the immune system can eliminate the tumor cells. On the other hand, the host response contributes to tumor progression by angiogenesis and metastasis. BRMs can regulate the host response to carcinogenesis by suppressing the tumor growth and metastasis.
Cytotoxic drugs can kill tumor cells directly, while biochemical modulators lack visible antitumor activity in their own right. There are 2 groups of biochemical modulators-chemosensitizers and chemoprotectants. Drug resistance is a major reason for poor responses and failures in cancer chemotherapy, while chemosensitizers can enhance the chemosensitivity to reduce drug resistance. Dose-limiting toxicity secondary to chemotherapy may reduce tumor control because of the inability to deliver adequate dose-intensive therapy against the cancer. However, chemoprotectants can provide protection for normal tissues, without compromising antitumor efficacy. They may allow the delivery of higher cumulative doses of cytotoxic agents without the expected consequence of toxicity.
Prescription composition of combined chemotherapy
In TCM theory, prescriptions are composed of 4 constituents, i.e., primary constituent (main component of the formula prescription), minister constituent (second component of the formula prescription), adjuvant constituent (adjuvant component of the formula prescription) and messenger constituent (component making formula prescription targeting pathological tissues), to make adequate use of the interaction of herbs to enhance therapeutic effects and reduce side reactions[2]. Correspondingly, we suggest that combined therapy in Western medicine may include four constituents: primary, cooperative, adjuvant and modulatory constituent. Cytotoxic drugs frequently are used as primary and cooperative constituents, whereas BRMs and biochemical modulators are usually regarded as adjuvant constituent and modulatory constituent respectively in combined therapy (Table 2). For example, chemotherapy combined with cisplatin, 5-Fluorouracil and folinic acid is the standard treatment for gastric cancer. 5-fluorouracil is a primary drug for gastric cancer and cisplatin has a cooperative antitumor effect with 5-fluorouracil. Folinic acid can reduce the side toxicity of 5-fluorouracil. So the primary, cooperative and modulatory constituents are 5-fluorouracil, cisplatin and folinic acid respectively (Table 3). Recently, immunotherapy has been regarded as part of combinations for the treatment of cancer, and high-dose chemotherapy with hematopoietic growth factor support has been used in high-risk patients with many cancers, such as breast cancer, lymphoma, acute myeloid leukaemia and small cell lung cancer[3-11].
Prescription composition of combined chemotherapy in Traditional Chinese Medicine and Western medicine.
Prescription of combined chemotherapy in Western medicine.
Conclusions
The interactions among drugs, tumor and patient are critical for a response to therapy and for outcome. So we suggest that anticancer drugs can be classified into 4 groups as their target (tumor, patient and drug): namely a cytotoxic drug, biological response modifier (BRM), chemosensitizer and chemoprotectant. Furthermore, we suggest that combined therapy in Western medicine might include 4 constituents, such as primary, cooperative, adjuvant and modulatory agents, to make adequate use of the interaction among drugs and modulate the interaction among the tumor, patient and drugs. In this way, a new combined therapeutic standard could be set up in Western medicine to continuously raise the medical level. We believe this new concept of combined therapy may be helpful for the goal of appropriately designing, evaluating or providing combination therapy.
- Received December 28, 2007.
- Accepted March 10, 2008.
- Copyright © 2008 by Tianjin Medical University Cancer Institute & Hospital and Springer
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