Clinical Implications of PSP in Oncology
T.F. Liu and W.C. Xue
Department of Radiation Oncology
Cancer Hospital, Shanghai Medical University
AbstractUp to now, the three main weapons against cancer have been surgery, radiotherapy and chemotherapy. Although these classical methods of treatment have given fairly good results in general, the results have yet to be improved, especially in late cases. Thus for many years, the search for a more effective means of anti-cancer treatment has been going on world-wide. An ideal drug would of course be one that could directly kill all the cancer cells without harming the normal tissues, and also without causing general toxicity. However, at present a more practical approach is to use drugs that would either enhance the biological effects of radiation or of cytotoxic agents, or strengthen the organism's immunological defenses. In recent years, several such drugs have been undergoing clinical trials, for example, Misonidazole, RS 2508, OK-432, PSK, etc.
The drug that we shall talk about today is polysaccharide peptide, hereafter referred to as PSP. This is a polysaccharide isolated from Coriolus versicolor by Professor Qing-yao Yang. It is similar in many ways to Krestin (PSK) discovered by the Japanese scientists in 1965. However, laboratory data, as well as both in vitro and in vivo experiments have shown that PSP is more active than PSK. Nevertheless, as a clinical oncologist, I must emphasize that any anti-cancer agent, no matter if the action is direct or indirect, must all undergo clinical trials to prove their value. It is well known that many drugs have been found to be very effective at the experimental level in animals, but when applied to human beings, due to unacceptable toxicity at effective doses, there was only limited practical value. Such examples are quite abundant in oncology: the radiosensitizer Misonidazole is a recent one. In the laboratory, an enhancement ratio of 1.7 of radiation effects was found in mice, but when used in patients, an E.R. of 1.2 could be barely achieved due to toxicity, and even then the late reactions of neurotoxicity made the drug unacceptable for clinical use. The presently widely used cancer chemtoherapy drugs such as Adriamycin and Cis-platinum have similar problems that limit their effectiveness.
Just as with PSK, basic investigations of PSP regarding toxicities and pharmacological activities have shown that by oral administration, no disturbances of peripheral blood picture, bone marrow, gastrointestinal tract, liver and kidney functions have been found so far. Marked effect has been demonstrated in animal experimental tumors.
In the Cancer Hospital of the Shanghai Medical University, Dr. Xue et al have treated 151 cases of various kinds of cancer, such as esophagus, lung, mediastinum, etc. First of all, two very important clinical aspects of PSP have been shown in the course of treatment of these cases. No drug toxicity has appeared clinically, and there has been noticeable, sometimes remarkable anti-cancer effect. These effects have been confirmed by many other colleagues who have used PSP on their patients. Such a combination is ideal for further clinical investigation, without the hazards associated in clinical trials with other agents.
There are several paths of clinical investigation that should be considered.
In our Department of Radiation Oncology, we have treated 4 cases of lung carcinoma with PSP, and found that growth of tumor, as shown by consecutive X-ray films, was stabilized as compared to 5 other cases without PSP treatment.
Very encouragingly, PSP has been shown to be of notable value in this respect. The experience of the Changzhou Municipal Hospital of Chinese Medicine has shown that PSP is effective in maintaining or even raising the WBC in 6 cases of advanced cancer treated by chemotherapy. The WBC had dropped to below 4000. PSP was able to raise them all to above 4000, in one case even to above 7000. In all the cases, the general condition was improved when PSP was given.
In our own cases, the value of PSP as an ajuvant treatment is quite evident, as Table 1 shows.
|Symptoms||No. of cases||Positive Effects||%|
|Relief of pain||44||37||84|
|Improvement of appetite||39||35||89|
|Less radiation reaction||5||4||80|
PSP has been shown to have immuno-potentiating properties. A preliminary investigation of immunological status in 10 of our patients treated by radiotherapy showed that the 5 patients receiving PSP had marked improvement in the post-radiation period as compared to the 5 controls.
In conclusion, in the pilot studies for PSP done on the clinical level, results have been very encouraging from all the various aspects including clinical effects against tumors, potentiation of effects in radiotherapy, chemotherapy and immunotherapy, as well as adjuvant symptomatic treatment. It is suggested that further Phase III trials be carried out under strict protocol, so that recognition and establishment of PSP as a new anti-cancer weapon will be achieved among oncologists all over the world.
|Per cent lymphocyte mitosis|
|Treament||Before RT||At end of RT||1 month after RT|
|Radiation + PSP||18||16||20.0|