CA-125 Changes Research Articles

Phase II trial of the oral PARP inhibitor olaparib (AZD2281) in BRCA-deficient advanced ovarian cancer

5500 Background: Olaparib (AZD2281; KU-0059436) is a novel, orally active PARP inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. A phase I trial identified 400 mg bd as the maximum tolerated dose (MTD) with an initial signal of efficacy in BRCA-deficient cancers (ASCO 2008; abst 5510). The primary aim of this study was to test the efficacy of olaparib in confirmed BRCA1/BRCA2 carriers with advanced chemotherapy-refractory ovarian cancer. The secondary aim was to assess the safety and tolerability profile in ovarian cancer patients with BRCA1/2 deficiency. Methods: In an international, multicenter, proof-of-concept, single-arm, phase II study, two patient (pt) sequential cohorts received continuous oral olaparib in 28-day cycles, initially at the MTD, 400 mg bd (33 pts), and subsequently at 100 mg bd (24 pts), a previously shown clinically active and PARP inhibitory dose. Eligibility criteria included confirmed genetic BRCA1/2 mutation and recurrent, measurable, incurable disease (previous chemotherapy, median 3 lines). The primary efficacy endpoint was best objective response rate (ORR; RECIST) post baseline. Change in CA125 was a secondary efficacy endpoint. All adverse events were reported using CTCAE v3. Results: At this interim analysis dated October 31, 2008, of 57 enrolled pts (39 BRCA1 deficient and 18 BRCA2 deficient), 33 were evaluable at 400 mg bd and 24 at 100 mg bd. The confirmed RECIST ORR was 33% at 400 mg bd and 12.5% at 100 mg bd. Clinical benefit rate (ORR and/or confirmed >50% decline in CA125) was 57.6% at 400 mg bd and 16.7% at 100 mg bd. Toxicity was mainly mild in severity, reflecting grade 1/2 nausea (44%); fatigue (35%); and anemia (14%). Grade 3 toxicity occurred infrequently, and comprised primarily nausea (7%) and leukopenia (5%). Conclusions: Oral olaparib is well tolerated and highly active in advanced, chemotherapy-refractory BRCA-deficient ovarian cancer, with greater activity seen at the higher dose. Toxicity in BRCA1/2 carriers was similar to that seen in non-carriers. This study provides positive proof of the concept of the activity and tolerability of genetically defined targeted therapy with olaparib in BRCA-deficient ovarian cancers. [Table: see text]

CA-125 change after chemotherapy in prediction of treatment outcome among advanced mucinous and clear cell epithelial ovarian cancers: a Gynecologic Oncology Group study.

There are limited data regarding unique clinical or laboratory features associated with advanced clear cell (CC) and mucinous (MU) epithelial ovarian cancers (EOC), particularly the relationship between CA-125 antigen levels and prognosis. A retrospective review of 7 previously reported Gynecologic Oncology Group phase 3 trials in patients with stage III/IV EOC was conducted. A variety of clinical parameters were examined, including the impact of baseline and changes in the CA-125 level after treatment of CC and MU EOC on progression-free (PFS) and overall survival (OS). Clinical outcomes among patients with advanced CC and MU EOC were significantly worse when compared with other cell types (median PFS, 9.7 vs 7.0 vs 16.7 months, respectively, P < .001; median OS, 19.4 vs 11.3 vs 40.5 months, respectively, P < .001). Suboptimal debulking was associated with significantly decreased PFS and OS among both. Although baseline CA-125 values were lower in CC (median, 154 micron/mL) and MU (100 micron/mL), compared with other cell types (275 micron/mL), this level did not appear to influence outcome among these 2 specific subtypes of EOC. However, an elevated level of CA-125 at the end of chemotherapy was significantly associated with decreased PFS and OS (P < .01 for all). Surgical debulking status is the most important variable at prechemotherapy predictive of prognosis among advanced CC and MU EOC patients. Changes in the CA-125 levels at the end treatment as compared with baseline can serve as valid indicators of PFS and OS, and likely the degree of inherent chemosensitivity.

A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer

Objectives Å6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered Å6 in women with epithelial ovarian cancer. Methods Women with epithelial ovarian, fallopian tube, or primary peritoneal cancer in clinical remission after first-line chemotherapy with 2 consecutive increases of CA125 values above normal but with no disease on physical examination or imaging studies were randomly assigned to receive daily subcutaneous injections of placebo, low-dose Å6 (150 mg), or high-dose Å6 (300 mg) until disease progression or end of study participation. Primary endpoints were time to clinical progression of disease and safety of Å6. Secondary endpoints were changes in serum CA125 and biomarkers of the urokinase system. Results Data are available for 24 women (placebo, n = 12; low-dose, n = 8; high-dose n = 4). Å6 therapy was associated with a statistically significant delay in time to clinical progression (log-rank p-value 0.01) with a median of 100 days (95% CI: 64,168) for women who received Å6 compared with 49 days (95% CI: 29,67) for women who received placebo. The treatments appeared to be well tolerated. Treatment was not associated with CA125 response ( p = 0.44). On-treatment values for plasma urokinase plasminogen activator receptor were statistically significantly lower in the Å6 groups compared with placebo ( p = 0.02). Conclusions Å6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population.

Effectiveness of ultrasound-guided aspiration and sclerotherapy with 95% ethanol for treatment of recurrent ovarian endometriomas

To evaluate the effectiveness of transvaginal ultrasound aspiration and ethanol sclerotherapy in patients with recurrent ovarian endometriomas. Retrospective study. Teaching hospital affiliated with Chang Gung University, Taipei. Patients (n = 108) with recurrent ovarian endometriomas >or=3 cm. Preoperative evaluation of previous pathology, midcycle serum CA-125 level, and color Doppler ultrasonography to exclude possibility of malignancies. After aspiration, sclerotherapy with 95% ethanol irrigation of the cystic cavity was performed (group 1, n = 78, 0-10 minutes of retention; group 2, n = 30, ethanol left in situ [retention]). Ultrasonography was performed at 3, 6, 9, and 12 months to determine persistence and size of cysts and the number of antral follicles. Pelvic pain score was also determined at those time points. The 1-year recurrence rate for group 2 patients was significantly lower than for group 1 patients (13.3% vs. 32.1%). Antral follicle count was increased and pain score was decreased in both groups to a similar level. No significant change in CA-125 was observed. Ultrasound-guided sclerotherapy with 95% ethanol is an effective therapy for ovarian endometriomas. Retention of ethanol is more effective than irrigation only.

Use of a novel biomarker HE4 for monitoring patients with epithelial ovarian cancer

5535 Background: The serum biomarker CA125 is effectively used for monitoring response to therapy and monitoring for recurrent disease in patients with epithelial ovarian cancer (EOC). However, CA 125 is not elevated in approximately 20% of patients. The novel tumor marker HE4 has been shown to be elevated in the majority of EOC patients as well as in patients that do not express CA125. The object of this study was to determine the concordance between HE4 and CA125 in patients being followed with EOC. Methods: This was a retrospective study utilizing serum samples obtained from an IRB approved serum bank. Serial samples from patients either undergoing treatment for EOC or being monitored for recurrence were obtained. Clinical status of the patients was assessed through serial CA125 and CT imaging with documentation of regression or progression of disease or absence of disease over time. Serum CA125 and HE4 levels were measured using the Architect CA 125II assay and the HE4 EIA assay. Serial changes in the serum CA125 and HE4 levels were compared to the documented clinical status using a cutoff of 25%. Concordance between HE4 and CA125 was determined and the performance of CA125 and HE4 was compared directly using a non-inferiority approach. Results: A total of 434 serial samples from 80 patients either undergoing treatment for EOC or being monitored for recurrence were obtained. Longitudinal analysis of the serum sample sets showed that changes in HE4 values were not inferior to changes in CA125 values in accordance with clinical status (p=0.039). CA125 correlated with clinical status in 78.8% (63/80) and HE4 correlated in 76.2% (61/80). In patients where CA125 did not correlate with clinical status, HE4 correlated in 23.5% (4/17). In patients where HE4 did not correlate with clinical status, CA125 correlated in 31.6% (6/19). In consideration of all cases either CA125 or HE4 correlated with clinical status for 83.8% (67/80). Conclusions: HE4 is a valuable biomarker for the majority of patients with EOC and behaves in concordance with CA125 in patients with EOC. As well, HE4 is a valuable marker for the management of some patients where CA125 is not of clincal utility. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Fujirebio Diagnostics, Inc Fujirebio Diagnostics, Inc, Thiel Statistical Consultants Fujirebio Diagnostics, Inc Fujirebio Diagnostics, Inc

Pegylated liposomal doxorubicin for epithelial ovarian cancer: The utility of Ca125 trends in guiding treatment decisions and subsequent response to platinum retreatment

16539 Background: In epithelial ovarian cancer early Ca125 changes guide clinical management decisions with rising trends prompting discontinuation of treatment. A retrospective review of case reco...

Lack of reliability of CA125 response criteria with anti‐VEGF molecularly targeted therapy

CA125 is an accepted indicator of epithelial ovarian cancer (EOC) response and is used to monitor patients treated with cytotoxic chemotherapy. It is uncertain how CA125 is affected by molecularly targeted drugs. In this pilot study, the authors analyzed the utility of CA125 to predict disease behavior in patients who were receiving sorafenib, a Raf-kinase/VEGFR2 inhibitor, and bevacizumab, an anti-VEGF monoclonal antibody. Fifteen of 42 patients had recurrent EOC. Patients received sorafenib 200 mg orally twice daily or D1-5 of 7 and bevacizumab 5 mg/kg to 10 mg/kg intravenously every 2 weeks for 28-day cycles. Computed tomography (CT) scans were performed every 2 cycles for restaging, and CA125 was measured monthly. CA125 concentrations were retrospectively analyzed as a function of clinical behavior. Fourteen of 15 patients had abnormal CA125 concentrations at study entry (median 1056 U/mL; range, 67 U/mL to 9813 U/mL). Seven (47%) patients had partial response by imaging criteria. Five of these 7 patients had partial response by CA125 criteria (71% sensitivity). Eight (53%) patients would have had partial responses if CA125 criteria were used; only 5 were confirmed by CT (63 % specificity). Imaging and CA125 criteria combined yielded a higher total response rate of 10 of 15 (67%). Three patients with objective partial response by imaging lasting >20, >22, and >24 cycles would have terminated treatment prematurely if CA125 had been used. CA125 changes may not correspond to imaging response criteria for EOC patients who are receiving sorafenib and bevacizumab. Caution is recommended when using CA125 as a response criterion of molecularly targeted agents until prospective studies validate CA125 changes with objective imaging response results.

Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer

Objective. To investigate the efficacy and safety of bevacizumab in heavily pretreated patients with recurrent ovarian cancer. Methods. Patients with recurrent ovarian cancer were treated with intravenous bevacizumab 10 mg/kg every other week plus oral cyclophosphamide 50 mg daily until disease progression or undue toxicity. Adverse events were graded according to the NCI Common Toxicity Criteria. Response rates were determined by CA-125 levels or changes in target lesions according to RECIST. Results. Fifteen patients were treated. Median age was 57 years (range 42–69). The median number of previous chemotherapy regimens was 8 (range 5–15). The median time from the first diagnosis to treatment with bevacizumab was 68.9 months (range, 26.5–177.2). The median number of bevacizumab infusions was 8 (range, 2–12), and the total number was 113. Two patients (13.3%) had a complete response after 4 months of therapy. Six patients (40.0%) had a partial response. The median duration of this response was 3.9 months (range, 2.3–10.4). Three patients (20%) had stable disease of 4.0, 5.2 and 5.5 months' duration, and 4 patients (26.7%) had progressive disease. Despite being heavily pre-treated and having confirmed intra-abdominal cancer, no gastrointestinal perforations developed. Other toxicities included: grade 3 pancreatitis in 1 patient; grade 2 proteinuria and hypertension in another, which resolved with the cessation of bevacizumab. Conclusion. In our population of very heavily pre-treated patients, with at least five prior regimens, bevacizumab in combination with oral cyclophosphamide has significant activity with a response rate of 53%, without significant toxicity.

Antiestrogen Therapy Is Active in Selected Ovarian Cancer Cases: The Use of Letrozole in Estrogen Receptor–Positive Patients

To evaluate the efficacy of the aromatase inhibitor letrozole in preselected estrogen receptor (ER)-positive relapsed epithelial ovarian cancer patients and to identify markers that predict endocrine-sensitive disease. This was a phase II study of letrozole 2.5 mg daily until clinical or marker evidence of disease progression in previously treated ER-positive ovarian cancer patients with a rising CA125 that had progressed according to Rustin's criteria. The primary end point was response according to CA125 and response evaluation criteria in solid tumors (RECIST) criteria. Marker expression was measured by semiquantitative immunohistochemistry in sections from the primary tumor. Of 42 patients evaluable for CA125 response, 7 (17%) had a response (decrease of >50%), and 11 (26%) patients had not progressed (doubling of CA125) following 6 months on treatment. The median time taken to achieve the CA125 nadir was 13 weeks (range 10-36). Of 33 patients evaluable for radiological response, 3 (9%) had a partial remission, and 14 (42%) had stable disease at 12 weeks. Eleven patients (26%) had a PFS of >6 months. Subgroup analysis according to ER revealed CA125 response rates of 0% (immunoscore, 150-199), 12% (200-249), and 33% (250-300); P = 0.028, chi(2) for trend. Expression levels of HER2, insulin-like growth factor binding protein 5, trefoil factor 1, and vimentin were associated with CA125 changes on treatment. This is the first study of a hormonal agent in a preselected group of ER-positive ovarian cancer patients. A signature of predictive markers, including low HER2 expression, predicts response.

Serum CA-125 in Relation to Adnexal Dysplasia and Cancer in Women at Hereditary High Risk of Ovarian Cancer

Serum CA-125 level is commonly used as indicator for ovarian cancer recurrence. However, its value for the prediction of neoplastic lesions is unknown. The aim of this study was to investigate whether CA-125 concentrations are indicative of adnexal dysplasia and cancer in women at hereditary high risk of ovarian/tubal cancer. CA-125 was obtained from 424 women at hereditary high risk of ovarian/tubal cancer attending the VU University Medical Center (Amsterdam, the Netherlands) between 1993 and 2005. Serum samples obtained at the second-to-last (n = 64) and last (n = 98) visit before surgery were tested in women who underwent adnexal surgery for diagnostic (n = 9) or prophylactic (n = 89) reasons. Serum samples obtained from 370 age-matched healthy women were used as controls. Both the absolute value (P < .0001) and the serial change (P < .0001) of CA-125 were predictive for ovarian cancer (n = 8). For adnexal dysplasia (n = 23), the absolute value of CA-125 (P = .003) was predictive, but the serial change in CA-125 was not (P = .32). The odds ratio for adnexal dysplasia versus nondysplasia in the highest tertile (CA-125 levels 14 U/mL) compared with the lowest tertile (CA-125 < 10 U/mL) was 6 (95% CI, 1.32 to 36.66). In patients at hereditary high risk for adnexal cancer, both the absolute value of serum CA-125 and the change in serial CA-125 are predictors for ovarian cancer. Remarkably, the absolute value of CA-125 is also predictive for adnexal dysplasia. CA-125 values should, therefore, be taken into account in the decision toward prophylactic bilateral salpingo-oophorectomy.

Early Changes in CA125 After Treatment with Pegylated Liposomal Doxorubicin or Topotecan Do Not Always Reflect Best Response in Recurrent Ovarian Cancer Patients

To examine early changes in CA125 relative to objective response in patients with recurrent ovarian cancer treated with pegylated liposomal doxorubicin (PLD) or topotecan and to compare the CA125 trends between the two chemotherapeutics. Patients with recurrent ovarian cancer, all of whom had measurable or evaluable disease, were randomized to receive 50 mg/m2 PLD every 28 days (n = 239) or 1.5 mg/m2 topotecan for 5 days every 21 days (n = 235) as part of a previously reported multicenter study. CA125 measurements were obtained prior to therapy and with each cycle of administration. Assessable patients underwent radiographic evaluation for response after two cycles of therapy. Objective responses were compared to trends in CA125 values at the end of cycles 1 and 2. CA125 changes were categorized as baseline (+/-10%), +/- 10%-25% variance, and > 25% variance. Among patients treated with PLD, 50% of complete responders (CR) and 41% of partial responders (PR) had increases in CA125 from baseline to cycle 1. Increases in CA125 were also seen in topotecan-treated patients; however, fewer patients had increases (20% and 8%, respectively). Overall, 15% of responding patients (CR + PR) receiving PLD and 6% receiving topotecan had elevated CA125 after two cycles of therapy. For those patients achieving a partial response, 19% of PLD-treated patients and 8% of topotecan-treated patients had CA125 levels above baseline at cycle 2. Considerable intrapatient variation in CA125 values is present among responding patients. Early increases in CA125 may not predict ultimate outcome, especially in PLD-treated patients.

A Phase I-II Preoperative Biomarker Trial of Fenretinide in Ascitic Ovarian Cancer

To evaluate study feasibility, toxicity, drug concentrations, and activity of escalating doses of the synthetic retinoid fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 and cytomorphometric biomarkers in cancer cells collected from ascitic fluid before and after treatment. Twenty-two naive patients with ascitic ovarian cancer were treated with escalating doses of 4-HPR at 0, 400, 600, and 800 mg/d for 1 to 4 weeks before surgery. Changes in the proportion of proliferating cells expressed by Ki67 and computer-assisted cytomorphometric variables (nuclear area, DNA index, and chromatin texture) were determined in ascitic cells. Drug levels were measured by high-performance liquid chromatography. Doses up to 800 mg/d were well tolerated, and no adverse reactions occurred. There was no effect of 4-HPR on changes in serum CA125, Ki67 expression, which were assessed in 75% of subjects, and cytomorphometric variables, which were assessed in 80% of subjects. Plasma retinol levels were significantly lower in affected women than healthy donors. 4-HPR plasma concentrations increased slightly with increasing doses and attained a 1.4 micromol/L concentration with 800 mg/d. Drug levels in malignant ascitic cells and tumor tissue were higher than in plasma but were 50 and 5 times lower, respectively, than in carcinoma cells treated in vitro with 1 micromol/L 4-HPR. Cell biomarkers can be measured in ascitic cells to assess drug activity. Under our experimental conditions, 4-HPR did not show activity in advanced ovarian cancer cells. However, clinical evidence supports further investigation of fenretinide for ovarian cancer prevention.

Perioperative CA19-9 Levels Can Predict Stage and Survival in Patients With Resectable Pancreatic Adenocarcinoma

Different prognostic factors stratify patients with pancreatic adenocarcinoma. The purpose of this study was to determine whether preoperative CA19-9 levels can predict stage of disease or survival and whether a change in preoperative to postoperative CA19-9 or the postoperative CA19-9 predicts overall survival. Four hundred twenty-four consecutive patients with pancreatic adenocarcinoma underwent resection between January 1, 1985 and January 1, 2004. Of the patients with a bilirubin less than 2 mg/dL, 176 had preoperative CA19-9 values, and 111 had pre- and postoperative CA19-9 values. Survival was measured from the first postoperative CA19-9 level measured (median, 39 days) until death or last follow-up. A multivariate failure time model was fit using clinical, operative, pathologic, and adjuvant treatment characteristics, and a categorization was defined by the values and changes in CA19-9 before and after surgery. Of the 176 patients, 128 (73%) had T3 lesions, and 99 (56%) had N1 disease; 138 patients (78%) underwent pancreaticoduodenectomy. Median preoperative CA19-9 levels were lower in N0 patients compared with patients with positive nodes (nine v 164 U/mL, respectively; nonparametric P = .06) and in T1/T2 patients versus T3 patients (41 v 162 U/mL, respectively; P = .03). Median follow-up time (n = 111) was 1.8 years (range, 1 to 12.9 years), with overall actuarial 1-, 3-, and 5-year survival rates of 70%, 36%, and 30%, respectively. Significant predictors of survival on multivariate analysis included a decrease in CA19-9 (P = .0005), negative lymph nodes (P = .001), lower T stage (P = .0008), and postoperative CA19-9 less than 200 U/mL (P = .0007). In patients with pancreatic adenocarcinoma, preoperative CA19-9 correlates with stage of disease. Both a postoperative decrease in CA19-9 and a postoperative CA19-9 value of less than 200 U/mL are strong independent predictors of survival, even after adjusting for stage. CA19-9 levels should be included in a patient's perioperative care and should be considered for prognostic nomograms.

CA125 response: can it replace the traditional response criteria in ovarian cancer?

CA125 is well established as an accurate and reliable means of monitoring response to treatment and confirming relapse in ovarian cancer patients. Its role in follow-up after initial treatment is less certain and the subject of a current clinical trial. Measuring response with computerized tomography scans is futile in the majority of patients, as disease is often nonmeasurable at presentation, e.g., ascites or peritoneal deposits, or all measurable disease has been removed at the time of surgery. Serial changes in CA125 can be used as a reliable indicator of disease response or progression so that patients can be classified as responding or progressing according to either standard or CA125 criteria. These precise definitions are currently being prospectively validated in conjunction with the new response evaluation criteria in solid tumor response guidelines and are being incorporated into all future clinical trials.

Predicting Response of Ovarian Cancer to Paclitaxel Treatment Based on Trend Analysis of Serum CA125

Recent randomized studies have reported significantly improved quality of life and survival in cancer patients who underwent tumor marker-directed treatment compared with patients treated according to Union Internationale Contre le Cancer (UICC) criteria [see Ref. (1) and references therein]. According to these studies, systematic analysis of tumor markers may document whether therapy is effective and should be continued in spite of its ultimate adverse toxic effects or whether it should be terminated because of ineffectiveness. The advantages of biochemical assessment are objectivity and reproducibility as well as the fact that tumor marker assays are subjected to longitudinal external and internal quality control. We aimed to determine whether changes in serum concentrations of the tumor marker CA125 evaluated by a newly developed algorithm predict response to chemotherapy in paclitaxel-treated ovarian cancer patients. Ovarian cancer patients with advanced disease (stage III at the time of diagnosis; n = 101; median age, 56 years; age range, 33–69 years) were enrolled in a prospective study monitoring changes in serum CA125 and the effect of therapy. Patients were treated with paclitaxel (Taxol; Bristol-Myers-Squibb) as part of a first-line combination chemotherapy. They received a median of six courses (range, three to nine) of chemotherapy. During a total of 689 chemotherapy cycles, serum CA125 concentrations were evaluated (AxSYM; Abbott Laboratories) and externally controlled through the CAPTMX tumor marker survey. Serum samples were obtained before starting therapy (specimen c ) and before each chemotherapy cycle (specimens c 1– c n). The univariate Cox regression model and the stepwise Cox regression model were used for selecting the optimal variables that most accurately predicted disease-free interval. The statistical package SAS, release 8.22 (SAS, Inc.), was used. The time-to-progression (TTP) in different patient groups was compared using Wilcoxon and log-rank tests. CA125 concentrations between groups of responders and nonresponders to …

Potential Clinical Utility of CA-125 in Responsive but Persistent Large-Volume Ovarian Cancer Following Platinum-Based Chemotherapy:

Background. Despite the demonstrated clinical utility of the serum CA-125 antigen level in ovarian cancer, controversy exists regarding interpretation of “discordant” results between changes in this tumor marker and measurable disease masses.Case. A patient with ovarian cancer cared for in the Gynecologic Cancer Program of the Cleveland Clinic Foundation receiving second-line single-agent carboplatin for recurrent disease demonstrated a major response in serum CA-125, but minimal shrinkage of a large painful abdominal mass. A laparotomy was performed both to define the nature of this mass and to attempt to relieve symptoms. The mass was found to be a large “inflamed pseudotumor with central necrosis.” No viable tumors cells were found.Conclusion. This case represents an excellent example of the remarkably complex biology of malignant disease and suggests how evaluation of changes in CA-125 in women with ovarian cancer may be utilized in individual patients to develop optimal management plans.

Effect of Topotecan on Serum CA-125 in Patients with Advanced Epithelial Ovarian Cancer

The effect of topotecan on CA-125 serum levels was evaluated in 30 patients with advanced epithelial ovarian cancer. All patients had progressive disease and were relapsing during (11 patients) or after (19 patients) chemotherapy containing paclitaxel and platinum. Topotecan (1.0 mg/m2/day) was administered intravenously on Days 1–5 every 3 weeks. The patients had received a median of 2 (1–5) prior regimens. Four patients had increased CA-125 only, and 26 had both measurable disease and increased CA-125. Two patients (7%) achieved a clinical partial response with durations of 5 and 10+ months, respectively. Eighteen other patients (60%) exhibited no clinical change with a median duration of 5+ months (range: 2–11+ months). Among these patients 9 (30%) had a biochemical response. The rate of change in CA-125 (s, slope of the exponential regression curve) during treatment with topotecan was compared with s over a period before treatment. A decrease in s was observed in 20 patients (74%). Comparing the mean values of s before and during topotecan, a significant (P = 0.005) decrease was seen in the CA-125 serum levels. The mean doubling times before and during treatment were 59 and 1421 days, respectively. Toxicity was mainly hematologic. Neutropenia grades III and IV were seen in 16 and 10 patients, respectively. No patients died due to side effects. Generally the side effects were mild to moderate. In conclusion, at the given dose intensity topotecan shows activity in advanced paclitaxel- and platinum-resistant ovarian cancer based on CA-125 measurements.

Comparison of Tumor-Associated Trypsin Inhibitor (Tati) with Ca125 as a Marker for Diagnosis and Monitoring of Epithelial Ovarian Cancer

Preoperative serum levels of CA125 and tumor-associated trypsin inhibitor (TATI) were measured in 220 patients undergoing laparotomy for adnexal masses. Of the 57 patients with epithelial ovarian cancer. 86% had serum CA125 higher than 35 kU/l and 81% higher than 65 kU/l while 51% had serum TATI above 22 micrograms/l. In eight patients with mucinous ovarian malignancies, serum levels of CA125 were above 65 kU/l in 6 cases while serum TATI was above 22 micrograms/l in 4 cases. Of the 163 patients with benign ovarian masses, 41% had serum CA125 levels above 65 kU/l and 17% above 65 kU/l whereas serum TATI was above 22 micrograms/l in 6%. In 11 cancer patients having elevated levels of both CA125 and TATI at diagnosis, the serum concentrations of these antigens were periodically measured during and after treatment. Changes in CA125 and TATI levels correlated with the clinical course in 84% and 37% of the instances, respectively. After the sixth course of chemotherapy, the diagnostic accuracy of the markers in the evaluation of the disease status at second-look laparotomy was 55% for CA125 with a cut-off level of 35 kU/l, 36% for a cut-off level of 65 kU/l, 55% for TATI, and 66% for the combination of CA125 and TATI with cut-off levels of 65 kU/l and 22 micrograms/l. CA125 is the most sensitive marker for epithelial ovarian cancer, but the concomitant measurement of TATI could be of benefit in both differential diagnosis of adnexal masses and monitoring of response of epithelial ovarian cancer to treatment.

CA-125 values predictive of clinical response during second-line chemotherapy for epithelial ovarian cancer.

Between November 1984 and January 1987, 19 patients with epithelial ovarian cancer were monitored with CA-125 values during second-line therapy. There was a statistically significant association between clinical response to therapy and CA-125 trend when trend was defined as a greater than or equal to 26% change in CA-125 from baseline value to last value prior to demonstration of clinical response (p = 0.0002). In 8 of 11 patients (73%), increasing CA-125 values were predictive of clinical progression during second-line therapy. In six of seven patients (86%), decreasing values predicted clinical regression. Three patients began second-line therapy with baseline values less than 35 U/ml. Two of these progressed during second-line therapy while the third progressed in follow-up. Two of four complete clinical responders completed second-line therapy with values less than 35 U/ml. Both progressed in follow-up with increasing CA-125 values. In this analysis, a 26% change in CA-125 values was a useful predictor of clinical response in patients receiving second-line therapy for epithelial ovarian cancer. Patients undergoing second-line chemotherapy with values less than 35 U/ml may still benefit from CA-125 monitoring.

Placebo-controlled study on serum concentrations of CA-125 before and after treatment of endometriosis with danazol or high-dose medroxyprogesterone acetate alone or after surgery

Serum concentrations of CA-125 were determined in association with 6-month medical (n = 48) or surgical and medical therapy (n = 40) of endometriosis. The concentration of CA-125 was significantly higher in stages III + IV (66.6 +/- 22.0 [standard deviation] U/ml) than in stage I (20.9 +/- 2.3 U/ml) or II (28.4 +/- 2.8 U/ml); in stage II, the concentration was higher than in stage I. Surgical elimination of endometriosis significantly decreased the level of CA-125, as did danazol, but not medroxyprogesterone acetate (MPA), although these drugs were equal in clinical efficacy. The CA-125 changes during hormonal treatment did not correlate with the clinical response. Postoperatively, CA-125 responses to danazol, MPA, or placebo did not differ significantly from each other. During the 6-month follow-up after medication, the CA-125 concentrations tended to increase, especially in danazol-treated women. The determination of CA-125 is useful in estimating the extent of the disease, but it is less valuable in monitoring the treatment effect. The ability of danazol to suppress CA-125 expression emphasizes the specific properties of this drug.