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Treatment with biologic response modifiers in patients with ovarian cancer
H Koelbl1, M Micksche, G Gitsch
12nd Department Obstetrics and Gynecology, University Hospital of Vienna, Austria.
Abstract:
The therapeutic and immunomodulating potential of biological response modifiers (BRM) such as OK-432 (a streptococcal preparation) and recombinant interferon gamma (rIFN-gamma) has been evaluated in 15 patients with advanced chemotherapy resistant ovarian cancer, presenting malignant ascites and/or pleural effusions. OK-432 was injected intracavitary in 10 patients in increasing doses from 0.2 up to 7.5 mg weekly. Five women were treated intracavitary with rIFN-gamma twice a week. The initial dose was 0.1 mg/m2 which was raised up to 12 mg/m2 over 6 weeks. With OK-432 a complete response was achieved for 14.1 + 8.9 months in 4 patients, a partial response for 1.7 + 0.3 months in 3 patients. The survival time of the 4 responders was significantly longer (21.1 + 8.3 months) than the survival time of the patients with partial or no response (4.9 + 2.7,4.1 + 2.3 months, respectively). In the rIFN-gamma therapy group, we found a partial response in one and no response in 4 patients. Toxicity observed under OK-432 and rIFN-gamma was minimal in all patients, suggesting a lack of systemic effect of intracavitary-applied BRM. With both agents, augmentation of certain immune responses, especially in the peritoneal cavity and to a lesser extent in the peripheral blood, has been documented. In 5 patients treated with OK-432, we found an overall augmentation of the effusion macrophage killer activity. rIFN-gamma augmented natural killer activity in 2 of 3 patients.
Insights
Biological response modifiers (BRM) like OK-432 and recombinant interferon gamma (rIFN-gamma) showed therapeutic potential in ovarian cancer patients with malignant effusions. Intracavitary BRM therapy demonstrated minimal toxicity and enhanced immune responses, improving survival in responders.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Advanced ovarian cancer with malignant ascites/pleural effusions is often chemotherapy-resistant.
- Biological response modifiers (BRM) are being explored for their therapeutic and immunomodulating effects in cancer treatment.
Purpose of the Study:
- To evaluate the therapeutic and immunomodulating potential of OK-432 and recombinant interferon gamma (rIFN-gamma) in patients with advanced chemotherapy-resistant ovarian cancer.
- To assess the efficacy, toxicity, and immune response augmentation of intracavitary BRM therapy.
Main Methods:
- 15 patients with advanced ovarian cancer and malignant effusions were treated with either OK-432 (n=10) or rIFN-gamma (n=5) via intracavitary injection.
- OK-432 doses ranged from 0.2 to 7.5 mg weekly; rIFN-gamma doses ranged from 0.1 to 12 mg/m2 twice weekly.
- Immune responses, including macrophage killer activity and natural killer (NK) cell activity, were monitored.
Main Results:
- Complete response (CR) to OK-432 was observed in 4 patients (lasting 14.1 months), with significantly longer survival (21.1 months) compared to partial (PR) or no responders.
- Partial response (PR) was achieved in 3 patients with OK-432 and 1 patient with rIFN-gamma.
- Minimal toxicity was noted for both agents, suggesting limited systemic effects. Immune responses, particularly in the peritoneal cavity, were augmented.
Conclusions:
- Intracavitary OK-432 and rIFN-gamma demonstrate therapeutic potential and immunomodulatory effects in advanced ovarian cancer with malignant effusions.
- BRM therapy is associated with minimal toxicity and can enhance local immune responses, leading to improved survival in responders.
- Further investigation into BRM as a treatment strategy for refractory ovarian cancer is warranted.