Treatment Of Malignant Effusion Research Articles

Treatment of malignant effusion by oncolytic virotherapy in an experimental subcutaneous xenograft model of lung cancer

BackgroundMalignant pleural effusion (MPE) is associated with advanced stages of lung cancer and is mainly dependent on invasion of the pleura and expression of vascular endothelial growth factor (VEGF) by cancer cells. As MPE indicates an incurable disease with limited palliative treatment options and poor outcome, there is an urgent need for new and efficient treatment options.MethodsIn this study, we used subcutaneously generated PC14PE6 lung adenocarcinoma xenografts in athymic mice that developed subcutaneous malignant effusions (ME) which mimic pleural effusions of the orthotopic model. Using this approach monitoring of therapeutic intervention was facilitated by direct observation of subcutaneous ME formation without the need of sacrificing mice or special imaging equipment as in case of MPE. Further, we tested oncolytic virotherapy using Vaccinia virus as a novel treatment modality against ME in this subcutaneous PC14PE6 xenograft model of advanced lung adenocarcinoma.ResultsWe demonstrated significant therapeutic efficacy of Vaccinia virus treatment of both advanced lung adenocarcinoma and tumor-associated ME. We attribute the efficacy to the virus-mediated reduction of tumor cell-derived VEGF levels in tumors, decreased invasion of tumor cells into the peritumoral tissue, and to viral infection of the blood vessel-invading tumor cells. Moreover, we showed that the use of oncolytic Vaccinia virus encoding for a single-chain antibody (scAb) against VEGF (GLAF-1) significantly enhanced mono-therapy of oncolytic treatment.ConclusionsHere, we demonstrate for the first time that oncolytic virotherapy using tumor-specific Vaccinia virus represents a novel and promising treatment modality for therapy of ME associated with advanced lung cancer.

Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer

Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment.

VEGF A, C, and D levels in malignant pleural effusions

22126 Background: Mayo data revealed that the median survival of patients with malignant pleural effusion is 4.7 months, with a 23% survival at one year and 7% at two years. These data emphasize the need for more preclinical research on ways to improve the diagnosis and treatment of malignant effusions. The purpose of this double-blind study was to ascertain VEGF A, C and D levels in various fresh pleural effusions. Methods: Sixty-four patients with cytology-known recurrent pleural effusions, who either underwent ultrasound-guided thoracentesis or fluid removal at the time of PleurX catheter placement. The effusions were centrifuged, aliquoted and frozen within 24 hours after removal. Each sample was evaluated for VEGF A, C and D levels using assay kits from ELISA-DuoSet by R&D in Minneapolis, MN. Results: Twenty-four non-malignant effusions and 40 malignant effusions including lung (15), breast (5), GI (6), ovarian (3), renal cell (3) and hematologic (8) were assayed. Assay findings (log transformed) were compared across groups using analysis of variance (ANOVA) with Dunnett's test used to compare each group to the non-malignant controls. Compared to controls (median VEGF A = 177), malignant effusions from adenocarcinomas had significantly elevated VEGF A with highest levels seen in renal cell carcinoma (median 6643), ovarian (median 4534), GI (median 4506), lung (median 3403) and breast (median 1577). Hematologic malignancies had low levels of VEGF A (median 107). Levels of VEGF C and D did not differ significantly across groups. Conclusions: Elevated levels of VEGF A in malignant effusions from adenocarcinomas may allow the use of the PleurX catheter as a means to treat and assess response to intracavitary antiangiogenesis therapies. No significant financial relationships to disclose.

Rapid pleurodesis with doxycycline through a small-bore catheter for the treatment of metastatic malignant effusions

The goal of the study was to evaluate the safety and efficacy of bedside pleurodesis with doxycycline using a short-term indwelling chest catheter for the palliative treatment of malignant effusions. A prospective study of 36 rapid pleurodesis procedures in 34 patients with malignant pleural effusions was conducted over a 5-year period in a university hospital. A 12F chest catheter placement was facilitated utilizing the Seldinger percutaneous entry technique. Patients received 500 mg of intrapleural doxycycline combined in half of the cases with mepivacaine. We assessed success or failure of pleurodesis in addition to the frequency of complications and survival. Chest tubes were removed within 24 h in 69% and within 48 h in 94% of the patients. Complete success of pleurodesis was achieved in 17 (55%), partial success in eight (26%), and failure in six (19%) out of 31 evaluative procedures. Thus, the overall success rate of pleurodesis was 81%. Toxicity was mild and included pain (36%), fever (8%), and pneumothorax (6%). The median survival was 105 days. There was no relationship between instillation of intrapleural anesthetics and development of pain. Rapid pleurodesis with doxycycline, which can be accomplished within 24 to 48 h, is a valid option for the symptomatic treatment of malignant effusions. This technique can be used as a first-line procedure in the majority of cases, particularly if thoracoscopic facilities are not available.

Combined chemotherapy in the treatment of malignant effusions.

Combined chemotherapy in the treatment of malignant effusions.

Thoracoscopic Management of Malignant Pleural Effusions

Malignant pleural effusion is a common condition and often presents a challenge for treatment. We report our experience from a single institution with the use of video-assisted thoracoscopic surgery (VATS) in the management of malignant effusions. From September 1992 to April 1995, 69 patients (31 men, 38 women; age range, 38 to 76 years) underwent diagnosis and/or treatment of malignant effusions; these included 46 pleural biopsies, 34 talc insufflations, and 16 limited decortications. There was no mortality and there were no intraoperative complications. Postoperative complications occurred in seven patients (10%). Specific histologic diagnoses were obtained in all but 6 patients (87%). Malignant effusion was confirmed in 25 of 46 cases (54%). Thoracoscopic talc insufflation with or without additional decortication was successful in 32 of 34 cases (94%) in controlling recurrence of effusion after a mean follow-up of 6 months among the survivors (22 patients died during the follow-up period without effusion reaccumulation). We conclude that VATS not only provides an accurate diagnosis but also allows effective therapeutic procedures to be performed for malignant effusions that are associated with an acceptable morbidity.

Intrapleural and intraperitoneal palliative treatment of malignant effusions with mitoxantrone

Intrapleural and intraperitoneal palliative treatment of malignant effusions with mitoxantrone

Local Adoptive Immunotherapy Using Lymphokine-activated Killer Cells and Interleukin-2 against Malignant Pleural Mesothelioma: Report of Two Cases

Malignant pleural mesothelioma is refractory to conventional therapy. We tried local adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) to control malignant pleural effusion due to mesothelioma in two patients: Case 1 was that of a 69-year-old man, and Case 2 that of a 49-year-old woman with complicating chronic idiopathic thrombocytopenic purpura. A systemic survey revealed no sign of metastasis in either case. Intrapleural instillations of 6.7 x 10(9) autologous LAK cells in Case 1, or 11.3 x 10(9) allogeneic LAK cells in Case 2, with daily injections of IL-2 resulted in reductions of the pleural effusions in each case and in a decline in the level of hyaluronic acid in the effusion, in Case 1. The instillations of autologous and allogeneic LAK cells were well tolerated. The results suggest that local adoptive immunotherapy could be useful in the treatment of malignant effusion due to mesothelioma.

Cytostatic activity of oxidized tetracycline in vitro: relevance for the treatment of malignant effusions?

Cytostatic activity of oxidized tetracycline in vitro : relevance for the treatment of malignant effusions?

Tetracycline in the treatment of malignant effusions: Evidence for a cytostatic action of the decomposed drug

During the in vitro growth of human carcinoma cell lines an inhibition of cell growth in media containing tetracycline was observed at a concentration which was about 1000 times below the one reached in the pleural fluid of malignant effusions after tetracycline instillation. During short time drug-cell contact only previously heated tetracycline showed growth inhibition like doxorubicine, a substance of similar structure and origin. Freshly prepared tetracycline inhibited cell growth only after several minutes of drug cell contact. Our observations in vitro suggest that decomposed tetracycline plays an important role in the control of malignant effusions.

Clinical Evaluation of A Percutaneous Pneumothorax Catheter

This study prospectively evaluates the efficacy and complications of the percutaneous pneumothorax catheter. Twenty-five patients were treated with the percutaneous catheter for 19 episodes of spontaneous or iatrogenic pneumothorax, six malignant effusions, and one infected bulla. The catheter was effective in all but a single episode of spontaneous or iatrogenic pneumothorax and was especially useful in three patients with tension pneumothorax. Further experience is required to define fully its feasibility in the treatment of malignant effusions or infected bullae. The ease of insertion, good response, and low incidence of complications suggest that this catheter may be a useful alternative to tube thoracostomy in selected situations.

Intracavitary Corynebacterium parvum for treatment of malignant effusions

Intracavitary instillation of Corynebacterium parvum was used to treat recurrent malignant effusions in 15 patients. Eleven patients were treated for ascites, and four patients were treated for pleural effusion. Six patients (40%) had good response with no recurrence of effusions up to 3 months after treatment. Three patients responded but died before criteria for complete response could be fulfilled. Six patients were judged to have poor response, either because of death from tumor burden before evaluation could be made or because of recurrent effusions. There were no serious side effects directly attributed to intracavitary C. parvum therapy. Analysis of the results in this preliminary study suggests that patients who have had prior good response to chemotherapy, whose performance scale is adequate, whose tumor burden is not preterminal, and who have been previously treated with immunotherapy may be excellent candidates for definitive treatment of malignant effusions with intracavitary C. parvum.

The effects of R 17934 (NSC 238159), a new antimicrotubular substance, on the ultrastructure of neoplastic cells in vivo

Ultrastructural investigations on 3 experimental neoplasms and on 1 human malignancy show that the in vivo antitumoral activity of R 17934 can be explained by its antimicrotubular properties. The induced disappearance of microtubules results in the disorganization and necrosis of dividing and non-dividing cancer cells. Mitotic normal cells (e.g., in the intestinal crypts) seem to be equally sensitive to the antimicrotubular action of R 17934, as malignant cells. Interphase normal cells however are much more resistant than their neoplastic counterparts. The lysosomotropic properties of the compound, when given as a micronized suspension, ensure a slow release effect and a local accumulation of the compound which can be favourably exploited in the treatment of malignant effusions.

A Study of Simultaneous Radioactive Gold and Cytostatic Therapy in the Treatment of Malignant Effusions

I. A combination of radiogold and cytostatic drugs appears to give the best results in the treatment of malignant effusions.II. No correlation could be found between the type of tumour and the response to therapy.III. Asymptomatic patients seem to respond better to either forms of therapy.IV. The lasting relief may occur after 6–12 instillations of cytostatic drugs following 198Au therapy.V. The longest relief experienced in the present study lasted 2 years and 4 months and occured after a single application of 198Au.

Effect of prednisone in the treatment of malignant effusions.

About 30% of the patients with metastatic malignancy develop significant effusions in the pleural, peritoneal, or pericardial cavities. 1 Rarely, the fluid has the characteristics of a transudate, as in some cases of mediastinal adenopathy, or a high content of fats, as in chylous effusions. More commonly, its physical properties resemble those of an exudate, with a specific gravity in the neighborhood of 1.016, a protein content higher than 3.5 Gm.%, and a high number of cells in the sediment. It was for the latter type of exudative effusions that the intracavitary administration of radioisotopes and alkylating agents was proposed; it was presumed that the effectiveness of this form of therapy was due to high local concentration of the cancerocidal agent coming into direct contact with the malignant tumor implants on the serosa surfaces. 2 In general, it is estimated that with either radioisotopes or chemotherapeutic agents it is possible