Malignant pleural effusion is a distressing complication in cancer patients with considerable management problems. A sclerosing agent, either antibiotic, antineoplastic, or radioactive can be delivered intrapleurally to produce mesothelial
fibrosis
and
obliterate small blood vessels, rather than produce specific antineopiastic activity. As previously described, the biological response modifier OK-432,a streptococcal preparation, has been to have clinical activities in malignant
pleuro-peritoneal
effusions.
To evaluate the clinical efficacy, 10KE of OK-432 dissolved in 50ml of normal saline was instilled in 16 patients with malignant pleural effusion via the chest tube drain. If necessary, instillations were repeated at one-week interval, one to
three
times. Peripheral blood lymphocytes of these patients ere evaluated sequentially for their natural killer(NK) and antibodydependent cellular cytotoxic(ADCC) activities before and after OK-432 instillation.
The age of patients ranged from 21 to 74 years with a median of 56 years, and the male to female ratio was 10:6. Ten patients had the lung primaries, and the other six primaries included stomach, uterine cervix rectum, liposarcoma of the chest
wall,
thymic carcinoma, and melanoma respectively, Cytologic examinations of the pleural fluid for malignant cells were positive in 5 patients.
Eleven patients(68.8%) showed an objective response and the duration ranged from 4+to 24 weeks with a median of 6+ weeks. Especially all 5 patients with positive pleural fluid cytology showed the response. Chest pain(13/25), and fever and/or
chills
(11/25) were the most common side effects. Other untoward effects included transient aggrevation of dyspnea(4/25), vomiting (4/25), anorexia(3/25), and general weakness(2/25). No patient showed the hypersensitivity reaction or reduction of blood
cell
counts.
Mean NK activity was markedly low in patients with malignant pleural effusion compare to that of 18 healthy volunteers (24.5*9.6% vs 47.6*6.4%) (P<0.01), but no difference in ADCC activity (50.9*14.5% vs 56.9*5.2%). The NK activity was enhanced
after
instillation of OK-432 (24.5*9.6% on day 0, 32.1*17.3% on day 1 through 3, and 42.4*26.0% on day 7) but their ADCC activities wee the same.
In a separate experiment, pleurae from the healthy rabbits were examined before and after intrapleural injection of OK-432. Varying dose of intrapleural OK-432 (1. OKE-10KE) did not cause any histologic change on the pleurae from the rabbits
which
were
sacrificed on day 7. No drug associated mortality was observed in the rabbits
OK-432 was effective to control the malignant pleural effusion especially in patients with positive pleural fluid cytology and showing augmentation of the NK activity in the peripheral blood. The side effects of the OK-432 was manageable. OK-432
did not
make any histologic change on the pleurae of the healthy rabbits.
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