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Ovarian cancer is the fourth leading cause of death from cancer in women and accounts for the highest mortality rate of all of the gynecological cancers (1). Despite aggressive treatment via radical surgery, radiotherapy, or chemotherapy, the mortality rate remains >50% for diagnosed patients. Although approximately 90% of stage IA (growth limited to the ovary) and 70% of stage IIA (metastases to the uterus or Fallopian tubes) tumors are curable if detected, 70% of women who are diagnosed with stage III and IV tumors have widespread intra-abdominal disease or distant metastases at diagnosis. For these patients, the cure rate plummets to 12 months after platinum therapy). To maximize the benefits of therapeutic regimens being tested in future clinical trials for ovarian cancer, an objective, reliable, and meaningful measure is required to assess end points.Characterized in 1981, the CA-125 antigen (38) remains the only serum tumor marker routinely used to test for epithelial cancer of the ovary (39). CA-125 is a membrane glycoprotein expressed by epithelial cells of different origins and thus is present in the serum of patients who have a variety of tumors. Different sites of glycosylation on CA-125 produce a heterogeneous mixture of varying molecular mass (mostly >1000 kDa) glycoproteins (40).The first method developed to measure CA-125 was a radioimmunometric assay that used the murine monoclonal antibody OC 125 as both capture and indicator antibodies (39). OC 125 was obtained after immunization with the OVCA 433 cell line, which was derived from the ascites fluid of a patient with papillary cystadenocarcinoma of the ovary (38). OC 125 recognizes the CA-125 epitope on a high molecular weight glycoprotein designated MUC 16. Monoclonal antibodies raised against other epitopes expressed by this molecule have led to the development of the CA-125-II assay, a variant of the original CA-125 assay that utilizes the M 11 monoclonal antibody as the capture antibody (41, 42). Both assays have proved reliable for measuring CA-125 levels in a number of benign and cancerous conditions, most notably ovarian cancer.Several studies document the similarities of sensitivity and specificity obtained with the original CA-125 and newer CA-125-II assays (43, 44). In addition to the very high correlation to the original CA-125 assay, the CA-125-II assay exhibits significantly less day-to-day variation and has better measurement characteristics for low CA-125 values (45). For the purposes of monitoring response to therapy, higher CA-125 values are generally observed and (over time) can be measured more precisely with the CA-125 II assay.CA-125 concentration is elevated most consistently in epithelial ovarian cancer, and its value has been demonstrated as a marker for patient prognosis, disease progression, and response to chemotherapy. At diagnosis, approximately 50% of patients who have stage I ovarian cancer and 90% of those with advanced-stage disease have elevated concentrations of CA-125 in their sera (2, 41, 46). However, CA-125 is expressed by a number of different cell types, both cancerous and noncancerous. Some patients with cancers of the lung, breast, endometruim, and gastrointestinal tract present elevated levels of CA-125, and CA-125 levels are also elevated in endometriosis, benign diseases of the liver and gastrointestinal tract, inflammation, and benign tumors of the ovary and uterus (47). Normal physiological conditions may also modulate CA-125 levels because concentrations are elevated slightly during menstruation (48) and more prominently during the first trimester of pregnancy.In clinical practice, CA-125 has important CA-125 in patients with a mass the of ovarian cancer, thus the patient a gynecological for chemotherapy, a CA-125 and patient that the tumor is CA-125 during chemotherapy can indicate development of drug This to an earlier or of therapy than if clinical criteria alone were CA-125 that is elevated but at the end of the of chemotherapy disease, but it remains this should be women in the have CA-125 levels measured during relapse, on months before is clinical evidence of However, is no evidence to that early treatment on a of CA-125 in an patient confers survival or An trial is whether early of chemotherapy relapse has been by an elevated CA-125 that can be to assess response to and subsequent of treatment. use obtained at of to indicate response and to indicate potential of CA-125 as a prognostic marker has been well and the biomarker has some in clinical trials that large of all ovarian cancer, the of CA-125 is about and studies have demonstrated that those patients with a of have a The of CA-125 before therapy has also been to be of prognostic These factors could be used to patients clinical trials.The rate of of CA-125 long-term response to therapy. For the individual patient, a serum CA-125 of measured before the of chemotherapy has been to be the most of early relapse or death the serum of CA-125 during chemotherapy is an prognostic marker for survival, rate of progression, time to progression, and the for a of progression rate of to 20% the value of these measurements for of individual patients. This of would inhibit the therapy of an individual patient but could be used in a clinical For if a high of patients in one of a trial had a CA-125 or higher CA-125 levels after of therapy, this would indicate the of that of therapy earlier than any other currently used an could an to determine whether to discontinue this treatment at an early time thus to therapy is an to trials with to early of the effective will benefit patients and an should be used if any of the are to cause disease than response for addition to its potential as a prognostic CA-125 has been to be as a for measuring tumor response to chemotherapy more patients who are first-line treatment are to CA-125 than those by used to assess standard or response criteria measurement of CA-125 is less and more for patients than In defined criteria for evaluating 50% and response to CA-125 in and these a 50% response to CA-125 is defined as a 50% in serum CA-125 as through a of CA-125 with elevated the that a 50% and a at the response is established if has been a in serum CA-125 levels of over In both the 50% and response the must be at after the previous recent the of response rates obtained using 50% and response definitions in of drugs in Phase II trials for ovarian cancer, compared with response rates obtained by standard criteria were obtained from treatment Phase II clinical trials of different drugs for relapsed ovarian cancer. Response rates were in patients to standard criteria and in patients to For each trial, the observed response rates as evaluation of the two criteria would in a Phase II trial, a target drug rate of 20% and a of was no response rate obtained by standard criteria and that obtained by CA-125 and therefore was no in whether a Phase II drug is active and in clinical this data on CA-125, its use in a clinical trial as a marker of response rate will have significant on the evaluation of new of any Phase II trial is to determine whether the of a drug is to continued and CA-125 measurement of tumor response has for clinical trial For the to discontinue a clinical trial or a therapeutic regimen can be early if the tumor response rate to CA-125 to a a trial that a response rate to CA-125 should be to include patients to be using both CA-125 and RECIST of CA-125 response rate could also be used to the less effective treatment to determine which should be is our that CA-125 response rate, using an should be in the of all clinical trials that evaluate therapy for ovarian cancer. The of response on CA-125 has been developed from clinical and with a has been the of by the Gynecologic Cancer a if would an of response than that has been to be an marker to define relapse of ovarian cancer The of of and the National Cancer has recently defined the date of progression to CA-125 using progression criteria These criteria are compared with the RECIST criteria in that CA-125 measurement be the of all ovarian cancer trials to define a date of disease progression for each patient. In addition to the number of patients for a trial, measurement of disease progression by CA-125 measurement with standard or RECIST criteria will the number of in the clinical In many progression defined using CA-125 will be earlier than progression established using RECIST data indicate that the is as an indicator of disease progression as the RECIST when used in a variety of clinical trials for or relapsed ovarian cancer Because of the of disease in ovarian cancer, an that measurements of CA-125 and measurable disease will provide a more of the tumor In certain an in progression-free survival using RECIST or CA-125 criteria should be to clinical benefit and should be used to of new drugs for ovarian for CA-125 measurement in has been proposed by CA-125 should be at each months for the first months after of chemotherapy. This can be increased to months for months and from years after the diagnosis. CA-125 in an patient is cause for but not treatment by The to on a CA-125 should be on the of CA-125 from a value the of should be the drugs clinical trials are to produce disease than with an rise in CA-125 levels who as progression to CA-125 are a particularly group in to test these is important that use of an elevated CA-125 as an with the of progression to CA-125 by the The to evaluating a drug would be to patients a test therapy and or no treatment. data in such a of patients, is a to for in fewer are potential as to could be to The is to use the response criteria only disease is one could for of that are for a as in a trial of and patients are CA-125 measurements months during the time from last CA-125 the to a the of can be used to the time therapy. This value can be compared with the time after a new therapy. from the treatment of the for and of Cancer CA-125 will clearly demonstrate the of the CA-125 rise over time in patients. These data will the of the CA-125 rise and the potential of before and after introduction of a novel this use of CA-125 can indicate for drugs in a Phase II it could be used to those drugs evaluation in would be to the CA-125 at the start of the new trial therapy as the CA-125 from that would be The time before progression could be the to CA-125 such as disease would require would require in different trials and against standard a of CA-125 levels is used as an the CA-125 not continue to rise at the rate monitoring of CA-125 will be required to a point the rise in CA-125 is significantly In this to that used for early of ovarian cancer with CA-125 values must be developed such as monitoring is therefore when any new definitions on are a large number of Phase II and Phase III clinical trials evaluating new and regimens of approved as well as new and drugs for treatment of ovarian cancer. The is to a of these and some of these trials have the CA-125 response rate criteria as well as the criteria for of progression-free survival Whereas much is required to or trial in of a Phase II trial using these criteria the and value of these methods for making in development of drugs for treatment of ovarian is currently a of data to the acceptance of CA-125 as a marker in clinical trials for the evaluation of drugs for ovarian cancer is our that CA-125 has numerous in the design of clinical from to of CA-125 as a biomarker for ovarian cancer will the number of patients for clinical trials in ovarian cancer. CA-125 should be as a that is to standard criteria for disease CA-125 measurement with RECIST therapies can be more and therapies can be These will benefit both the patient and the data that demonstrate the utility of a drug on progression-free survival to CA-125 and RECIST criteria proposed by the should be used to of therapies. therefore the following with to CA-125 in clinical trials for ovarian CA-125 should be used routinely in Phase II clinical trials to for to determine response rates using both CA-125 criteria and RECIST criteria would be designed that if the CA-125 response rate is than a that has 90% to the rate, the trial would be continued that response can be measured with the by RECIST should be that in trials of chemotherapy early CA-125 response is to both and these values should not be as response to chemotherapy. Because the CA-125 is the CA-125 response to should no be a by the start of the of treatment. treatment of trials of therapy should the of patients with CA-125 levels the of at the start of their of chemotherapy from or CA-125 of should be for early of those with significantly defined by Progression-free survival the date of progression should be defined to the CA-125 and RECIST criteria proposed by the CA-125 should be in Phase I and II trials to the optimal and of therapies such as signal Several methods for and evaluating response criteria for these newer drugs are and their is and should be the of and new such as and should aid for both Phase II and pivotal trials and could be end points to CA-125 in evaluating new ovarian cancer therapies. may be to to therapeutic response for which assays could be These assays could new therapies, trial data that demonstrate CA-125 response defined and in previous and an in progression-free survival defined to the CA-125 and RECIST criteria proposed by the should be used to of therapies. These trials would be designed to allow of evaluation to survival or quality of life end points or to be in Phase IV trials using these standard end for of Cancer
Rustin et al. (Tue,) studied this question.