CLINICAL APPLICATION AND POSSIBLE FUTURE TRENDS

VIII. CLINICAL APPLICATION AND POSSIBLE FUTURE TRENDS

Lentinan appears to be a unique immunological adjuvant with no toxic side effects on in vivo application. It was found to have distinct antitumor and metastasis-inhibiting effect in allogenic, syngenic, and autochthonous hosts, and its mode of action has been elucidated. Several studies have been done on the antitumor activity of L. edodes (7,21,22,26,31–34,36,37,39,42,44– 47,49,67,133–136) and it has been widely accepted that activated macro- phages, cytotoxic T cells, natural killer cells, and killer T cells usually play important roles in the immunity against tumor. Lentinan has been reported to enhance the activity of these immune systems and its antitumor activity is activated through a host-mediated immune response (10,20,21,45,71,76,137– 139). Hence, lentinan shows great potential as a candidate for effective therapy of cancer patients.

Several studies have shown the safety of soluble h-glucans and the absence of undesirable side effects (21,26,45,71,137). Studies involvinganimal models revealed that the LD 50 is over 2500 mg/kg by intraperitoneal and 250– 500 mg/kg via intravenous administration in mice and rats (26). Yap and Ng (22) and Sudhir and Ng(132) also observed no weight loss in the experimental mice experiment over a period of 1 month.

Clinical trials usinglentinan in combination with chemotherapy have shown encouraging results (41,42,52,53,135,134). Taguchi (42), investigating the clinical application of lentinan, has carried out Phase I, II, and III studies of randomized control clinical trials. Results of a 4-year follow-up Phase III randomized control study of lentinan patients with advanced and recurrent stomach and colorectal cancer revealed that the combination therapy of lentinan with tegafur led to the prolongation of their life span. Increment in survival time and complete cure of micrometastases after surgical resection in cancer patients could also be achieved by usinglentinan (64,140,141).

Human cancer is a disease with great diversity as compared to other infectious diseases. The tumor-host relationships may differ, dependingon the stage of tumor growth, as well as the course of treatments. Hence, the use of lentinan for human cancer should be based on strict administration timing and dosage schedules in compliance with the immunological and biological changes that were observed in lentinan-treated animals. The effect of lentinan in the treatment of human cancer is increased when it is used in conjunction with other therapies, especially after surgical resection. An important field of

354 Yap and Ng

study may be to determine the parameters for tumor-host relationships, which can then be used as indicators for the design of protocols on the use of im- munopotentiators such as lentinan.

ACKNOWLEDGMENT The authors are grateful to the National University of Singapore for the

research grant (R-182-000-018-112). Thanks to Ms. R. K. Bhuvana for her kind assistance in verification of the bibliography and to Miss Patricia Netto for preparingthe figures.

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