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[Modulation of anticancer effects of immunochemotherapeutic agents in various nutritional environments]
M Akimoto1, T Nishihira, S Mori
12nd Dept. of Surgery, Tohoku University, School of Medicine.
Abstract:
It is well known that some kinds of immunological functions, s.c. NK activity, IFN or IL-2 production of spleen cells are decreased in mice with protein calorie malnutrition (PCM) compared with those of well-nourished mice. In this study, nutritional conditions of cancer bearers were demonstrated to have serious influence on the effects of immunochemotherapeutic agents as shown herewith. (1) Intra-tumoral 5-FU concentration was lower in PCM mice or starved mice than in mice fed a normal diet. (2) Transplanted mammary tumor, MM-48, was paradoxically grown in PCM mice after 7 days i.p. injection of OK-432 or Lentinan, but the tumor burden was relatively decreased after the same treatment in N-group mice. (4) The life prolongation effect of rIL-2 and OK-432 against ascitic hepatic carcinoma, MH-134, was recognized in C 3H/He mice. On the other hand, there was no observable effect by sequential i.p. injection of PCM mice sera together with rIL-2 and OK-432. (5) Clinically, a randomized study of advanced or recurrent gastric cancer patients treated with MMC and FT(MF) with or without Lentinan was performed. Excellent end-point results were obtained only in Lentinan-administered patients with normal protein levels, but no such effects were noted in patients with low protein levels (below 5.9 g/dl). These findings suggest that the nutritional environment of the cancer bearing host has an important role in the effect of some kinds of BRMs.
Insights
Protein calorie malnutrition (PCM) impairs immune function and reduces the efficacy of cancer immunotherapies. Nutritional status significantly impacts treatment outcomes for cancer patients, highlighting the importance of host nutrition in BRM therapy.
Area of Science:
- Immunology
- Oncology
- Nutritional Science
Background:
- Protein calorie malnutrition (PCM) is known to impair immunological functions like NK activity and cytokine production.
- Nutritional status in cancer patients can significantly influence the effectiveness of immunochemotherapeutic agents.
Purpose of the Study:
- To investigate the impact of nutritional status on the efficacy of immunochemotherapeutic agents in cancer bearers.
- To evaluate how protein-calorie malnutrition affects drug concentration, tumor growth, and survival in cancer models and patients.
Main Methods:
- Animal models (mice) with induced PCM or starvation were used to assess intra-tumoral drug concentration, tumor growth, and survival after treatment with 5-FU, OK-432, Lentinan, and rIL-2.
- A randomized clinical study evaluated advanced/recurrent gastric cancer patients treated with MMC and FT(MF) with or without Lentinan, correlating outcomes with serum protein levels.
Main Results:
- Intra-tumoral 5-FU concentration was lower in PCM or starved mice.
- Tumor growth was paradoxically enhanced in PCM mice treated with OK-432 or Lentinan, while tumor burden decreased in normally nourished mice.
- Therapeutic effects of rIL-2 and OK-432 were diminished in PCM mice.
- Clinical study showed positive outcomes with Lentinan only in gastric cancer patients with normal protein levels.
Conclusions:
- Host nutritional status critically influences the efficacy of certain biological response modifiers (BRMs) and immunochemotherapies.
- Maintaining adequate nutritional levels is crucial for optimizing cancer treatment outcomes, particularly when using BRMs.
- Further research into the interplay between nutrition and cancer therapy is warranted.
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