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International Journal of Oncology Jun 2008The prognosis for patients with ovarian cancer is still poor and more effective therapeutic modalities are needed. (Radio)immunotherapy using monoclonal antibodies... (Review)
Review
The prognosis for patients with ovarian cancer is still poor and more effective therapeutic modalities are needed. (Radio)immunotherapy using monoclonal antibodies (Mabs) could be one of these approaches. Here, we review the status of (radio)immunotherapy using Mabs for the treatment of ovarian cancer. The Pubmed database was searched for clinical trials investigating the effect of (radio)immunotherapy in ovarian cancer published until October 1, 2007. Keywords for the search were: ovarian cancer, monoclonal antibodies, CA 125, gp38, HER2, HMFG, MUC1, TAG 72 and VEGF. A total of 44 trials on immunotherapy with unconjugated Mabs, Mab vaccination and (radio)immunotherapy directed towards the antigens CA 125, gp38, HER2, MUC1, TAG 72 or VEGF in patients with ovarian cancer were found, reviewed and discussed. Out of these trials, 23 studied immunotherapy with unconjugated Mabs, 5 vaccination with Mabs and 16 trials studied (radio)immunotherapy. The lack of large randomized prospective trials with Mabs directed to tumor-associated antigens expressed on ovarian cancer cells preclude any firm conclusion on the potential of Mabs use in the treatment of ovarian cancer. Oregovomab, directed against CA 125, and bevacizumab, targeting VEGF, are two unconjugated Mabs closest to clinical introduction for the treatment of ovarian cancer. Vaccination with Mab ACA 125 seems promising but these findings need to be confirmed in controlled randomized trials. Sole RIT should be investigated with the appropriate radionuclide and a Mab with high affinity for the specific tumor-associated antigen in the appropriate patient group to determine whether it may have a therapeutic effect. Additionally, appending (radio)immunotherapy with anti-TAG 72 or anti-MUC1 to other treatment strategies such as chemotherapy could also be a strategy worthwhile investigating. The potential of Mabs to complement current treatment paradigms, is encouraging and may bring a significant improvement to the overall therapeutic outcomes currently being achieved in ovarian cancer.
Topics: Antibodies, Monoclonal; Clinical Trials as Topic; Female; Humans; Immunotherapy; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms
PubMed: 18497976
DOI: 10.3892/ijo_32_6_1145 -
Cancer Management and Research 2019The number of published randomized clinical trials (RCTs) using targeted maintenance therapy for newly diagnosed epithelial ovarian cancer is increasing. Our objective...
The number of published randomized clinical trials (RCTs) using targeted maintenance therapy for newly diagnosed epithelial ovarian cancer is increasing. Our objective was to evaluate the comparative effectiveness of each maintenance therapy using a network meta-analysis. A systematic search for RCTs was conducted using Medline, Embase, and CENTRAL databases followed by a Bayesian network meta-analysis. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS). Pooled hazard ratios (HRs) with 95% credible intervals (95% CrIs) were used to estimate outcomes. A total of 11 RCTs involving 6631 patients were included. Network meta-analysis showed that pure maintenance therapy with pazopanib resulted in a significantly better PFS compared with placebo (HR, 0.77; 95% CrI, 0.65-0.92). Bevacizumab-throughout treatment was also associated with a better PFS (HR, 0.76, 95% CrI, 0.69-0.84). However, anti-CA-125 monoclonal antibodies (abagovomab and oregovomab) showed no significant survival benefit. Moreover, combined analysis showed that targeted-throughout was not significantly superior to pure targeted maintenance therapy for PFS and OS. Stratified analysis showed paralleled results with no significant difference between pazopanib pure maintenance and bevacizumab-throughout treatments. Our study showed a survival advantage conferred by pazopanib and bevacizumab as maintenance therapy in newly diagnosed epithelial ovarian cancer. Further clinical trials are essential to both determine the effect of bevacizumab in the maintenance stage and identify the specific subgroup(s) that benefit.
PubMed: 31190984
DOI: 10.2147/CMAR.S187119 -
PloS One 2018Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer.
METHODS
Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted.
RESULTS
Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64-0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53-0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73-1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95).
CONCLUSION
Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers?
Topics: Adjuvants, Pharmaceutic; Antineoplastic Agents; Aspirin; Decision Making; Evidence-Based Medicine; Humans; Neoplasms; Observational Studies as Topic; Treatment Outcome
PubMed: 30252883
DOI: 10.1371/journal.pone.0203957 -
Cancer Immunology, Immunotherapy : CII Jul 2020The original version of this article unfortunately contained a mistake.
Correction to: Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients.
The original version of this article unfortunately contained a mistake.
PubMed: 32219502
DOI: 10.1007/s00262-020-02537-4 -
Journal of Pharmacy & Pharmaceutical... 1998PURPOSE. This article reports the pharmacokinetics, radiation dosimetry and radioimmunoscintigraphy (RIS) of two (99m)Tc-labelled monoclonal antibodies (MAb) used to... (Clinical Trial)
Clinical Trial
UNLABELLED
PURPOSE. This article reports the pharmacokinetics, radiation dosimetry and radioimmunoscintigraphy (RIS) of two (99m)Tc-labelled monoclonal antibodies (MAb) used to detect cancer.
METHODS
The effects of circulating antigen in female cancer patients are explored and their effects on the ability of these MAbs to effectively perform as RIS agents noted. To illustrate the effects of circulating antigen, data using MAb B43.13 (OVAREX, AltaRex Corp., Waltham, MA, USA) from a Pilot study in ovarian cancer patients are presented. The results from a Phase II study of MAb 170H.82 (Tru-Scint AD, BIOMIRA INC., Edmonton, Alberta, Canada) in patients with primary and locally recurrent breast cancer were used to portray the biodistribution patterns when no circulating antigen is present. Data from planar gamma camera images were obtained for both groups and used for pharmacokinetic and radiation dosimetry analyses.
RESULTS
A pharmacokinetic analysis indicated a shorter residence time and higher clearance of (99m)Tc-MAb-B43.13 that was ascribed in part to the circulating CA 125 antigen in this group of ovarian cancer patients.
CONCLUSION
These clearance patterns resulted in acceptable, though higher radiation doses to the spleen and urinary bladder wall for these patients when compared to the MAb-170H.82 group. Both MAbs were found to produce acceptable radioimmunoscintigraphic images
Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Breast Neoplasms; CA-125 Antigen; Female; Humans; Image Processing, Computer-Assisted; Middle Aged; Organotechnetium Compounds; Ovarian Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution
PubMed: 10948399
DOI: No ID Found -
Cancer Immunology, Immunotherapy : CII Sep 1998The use of biodegradable poly(DL-lactic-co-glycolic acid) microspheres as a cancer vaccine delivery system for induction of anti-idiotypic responses was investigated...
Induction of anti-idiotypic humoral and cellular immune responses by a murine monoclonal antibody recognizing the ovarian carcinoma antigen CA125 encapsulated in biodegradable microspheres.
The use of biodegradable poly(DL-lactic-co-glycolic acid) microspheres as a cancer vaccine delivery system for induction of anti-idiotypic responses was investigated using a murine monoclonal antibody B43.13 that recognizes the human ovarian cancer antigen CA125. Immunization of mice with mAb B43.13 encapsulated in poly(DL-lactic-co-glycolic acid) microspheres resulted in enhanced humoral and cellular immune responses compared with mAb B43.13 alone or mAb B43.13 mixed with microspheres. The antibody responses could be further enhanced by the co-encapsulation of mAb B43.13 with monophosphoryl lipid A, a non-toxic adjuvant, in microspheres. Anti-idiotypic humoral responses were shown to result in Ab2 antibodies mimicking the nominal antigen CA125 and Ab3 antibodies recognizing CA125. Further, microsphere delivery of mAb B43.13 also resulted in induction of T cell responses involving T2 cells reactive with mAb B43.13 epitopes and T3 cells recognizing CA125. These results indicate that microsphere delivery of Abl can induce both humoral and cellular anti-idiotypic responses relevant to cancer antigens. This raises the possibility of the use of such formulations for anti-idiotypic induction immunotherapy for cancer.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antibody Formation; Biocompatible Materials; CA-125 Antigen; Female; Humans; Immunity, Cellular; Lactic Acid; Mice; Mice, Inbred BALB C; Microspheres; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; T-Lymphocytes
PubMed: 9755874
DOI: 10.1007/s002620050499