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

PURPOSE: Twenty-one–day topotecan infusion was administered as second-line therapy in patients with previously treated ovarian cancer (based on our prior favorable phase I experience) to determine its activity, time to progression, and pharmacodynamics. PATIENTS AND METHODS: Ovarian cancer patients with measurable lesions and one prior platinum-containing regimen were eligible. Topotecan 0.4 mg/m2/d 21-day continuous ambulatory intravenous infusion, with appropriate dose modifications for toxicity, was administered every 28 days. Weekly blood levels of topotecan and topoisomerase-1 (topo-1) levels in peripheral-blood mononuclear cells (PBMCs) were determined for pharmacodynamic correlation. RESULTS: Twenty-four patients were entered onto the study (six cisplatin-refractory, five relapsing within < 6 months and 13 relapsing > 6 months after platinum-based therapy). A total of 128 cycles of topotecan (median, four cycles per patient; range, one to 12 cycles) were administered. The major toxicity was neutropenia (29% grade 3 in all cycles and 4% grade 4). One episode of grade 4 thrombocytopenia (4%) occurred. Fifty-two percent of the patients had anemia that required transfusions. Eight of 23 patients with measurable disease (35%; 95% confidence interval [CI], 15% to 54%) had partial responses (PRs) lasting longer than 1 month. Two of these patients had minor residual computed tomographic changes but had clinical complete remissions that lasted up to 53 weeks while they were not undergoing further therapy. One patient with nonmeasurable disease had a PR (by CA-125 criteria) that lasted 6 months, for an overall response rate of 38% in nine of 24 patients (95% CI, 18% to 57%). The median time to progression was 26 weeks. Pharmacodynamic analysis demonstrated a statistically significant decrease in free PBMC topo-1 level at weeks 2 and 3 of drug administration. There was a strong statistical correlation between the decrease in free topo-1 levels and increasing area under the curve (AUC) for topotecan. This was confirmed in a pharmacodynamic model. CONCLUSION: Twenty-one–day infusion is a well-tolerated method of administering topotecan. Pharmacodynamic studies demonstrate correlations between (1) the week of infusion and the PBMC topo-1 level, (2) the AUC of topotecan and the decrease in topo-1 levels, and (3) the change in topo-1 level and the neutrophil nadir. The objective response rate of 35% to 38% (95% CI, 15% to 57%) in this small multicenter study is at the upper level for topotecan therapy in previously treated ovarian cancer. Prolonged topotecan administration therefore warrants further investigation in larger, randomized studies comparing this 21-day schedule with the once-daily-for-5-days schedule.

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Phase II study of gemcitabine and oxaliplatin in patients with recurrent ovarian cancer: an Australian and New Zealand Gynaecological Oncology Group study

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2007.00763.x ◽

2007 ◽

Vol 17 (2) ◽

pp. 359-366 ◽

Cited By ~ 15

Author(s):

P. Harnett ◽

M. Buck ◽

P. Beale ◽

A. Goldrick ◽

S. Allan ◽

...

Keyword(s):

Ovarian Cancer ◽

Single Agent ◽

Recurrent Ovarian Cancer ◽

Ca 125 ◽

Platinum Sensitive ◽

Best Response ◽

Platinum Based Chemotherapy ◽

Group A ◽

Intent To Treat ◽

Group B

Gemcitabine and oxaliplatin have shown single-agent activity in relapsed ovarian cancer. This combination was used to determine response rates, time-to-event efficacy measures, and toxicity in patients with recurrent ovarian cancer. Patients with prior platinum-based chemotherapy who had measurable lesions and/or elevated CA-125 levels were identified as group A (platinum-refractory/platinum-resistant patients) and group B (platinum-sensitive patients). All patients received gemcitabine 1000 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days for up to eight cycles. Seventy-five patients (21 in group A and 54 in group B), with a median age of 58 years (range, 37–78), were enrolled. A median of six cycles (range, 1–8) was administered. By intent-to-treat analysis, 15 patients with measurable disease achieved partial response for an overall best response rate of 20.0% (9.5% in group A and 24.1% in group B). CA-125 response was observed in 48.4% patients (30.0% in group A and 57.1% in group B). Median time to progressive disease was 7.1 months (95% CI, 5.6–9.0 months) with 5.0 months in group A and 8.3 months in group B. Median overall survival was 17.8 months (95% CI, 12.9–21.3 months) with 9.2 months for group A and 20.0 months for group B. Major grade 3/4 toxicities were neutropenia (61.3%), leukopenia (24.0%), nausea (16.0%), and vomiting (22.7%). We conclude that the combination of oxaliplatin and gemcitabine is active in patients with recurrent ovarian cancer, but the regimen is unsatisfactory for further study due to modest response and relatively high toxicity.

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Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type: The PaLiDo study, a phase II nonrandomized multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.5052 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 5052-5052 ◽

Cited By ~ 1

Author(s):

Karina Dahl Steffensen ◽

Marianne Waldstrøm ◽

Niels Pallisgaard ◽

Bente Lund ◽

Kjell Bergfeldt ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Liposomal Doxorubicin ◽

Response Rate ◽

Pegylated Liposomal Doxorubicin ◽

Ca 125 ◽

Wild Type ◽

Platinum Resistant ◽

Platinum Based Chemotherapy ◽

Dermatologic Toxicity

5052 Background: Ovarian cancer (OC) patients with platinum-resistant recurrent disease have few therapeutic options and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. The main purpose was to investigate the response rate in platinum-resistant, KRAS wild-type OC patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. Methods: Major eligibility criteria were confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end of first or second line platinum-based chemotherapy. Only patients with measurable disease by CA125 criteria and with KRAS wild type were eligible. Patients were treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m² day 1, every 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CA-125 criteria. Results: A total of 46 patients were enrolled by 6 study sites in this multi-institutional phase II trial. Within the population evaluable for response (N=33), there was 8 CA125 responders for an overall response rate of 24.3 %. Progression-free and overall survival in the intention-to-treat population (N=43) was 2.7 months (2.5-3.2 months, 95%CI) and 8.1 months (5.6-11.7 months, 95%CI), respectively. The most common treatment related grade 3 toxicities included skin toxicity (42%), fatigue (19%) and vomiting (12%). Conclusions: The combination of PLD and panitumumab demonstrates efficacy in platinum refractory/resistant patients although the dermatologic toxicity was considerable.

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Phase 2 trial of tisotumab vedotin in platinum-resistant ovarian cancer (innovaTV 208).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps5602 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS5602-TPS5602 ◽

Cited By ~ 1

Author(s):

Haider Mahdi ◽

Steven Robert Schuster ◽

David M. O'Malley ◽

Donna M. McNamara ◽

Reshma A. Rangwala ◽

...

Keyword(s):

Ovarian Cancer ◽

Primary Endpoint ◽

Human Monoclonal Antibody ◽

Single Agent ◽

Ca 125 ◽

Phase 2 ◽

Phase 2 Trial ◽

Platinum Resistant ◽

Platinum Based Chemotherapy ◽

Increased Risk

TPS5602 Background: Ovarian cancer (OC) is the most lethal gynecologic cancer, accounting for ≈185,000 deaths worldwide in 2018. Most patients (pts) initially respond to platinum-based chemotherapy (chemo), but more than 50% of pts recur. Pts who recur in ≤6 months have platinum-resistant OC (PROC), which is associated with poor prognosis. Standard therapy for PROC includes chemo ± bevacizumab (bev). However, many pts receive single-agent chemo, which demonstrates limited response and survival (≈12% ORR, 3-4 mo PFS, ≈12 mo OS). Therefore, there is an urgent need for novel therapeutic strategies. Tissue factor (TF) is a novel oncogenic target expressed in OC. Tisotumab vedotin (TV) is a first-in-class antibody drug conjugate comprising a TF-targeted fully human monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. TV has shown encouraging antitumor activity and a manageable safety profile in PROC in the multicohort phase 1/2 innovaTV 201 study. innovaTV 208 is a multicenter, open-label, phase 2 trial with a safety run-in phase for a dose-dense regimen (DDR) evaluating the efficacy and safety of TV in pts with PROC. Methods: innovaTV 208 will enroll ≈142 adult pts with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer; measurable disease by RECIST v1.1; and ECOG score 0-1. Eligible pts must have received bev-containing treatment for OC. Pts with platinum-refractory disease, increased risk of bleeding, active ocular surface disease, or grade > 1 peripheral neuropathy will be excluded. A safety run-in phase for the DDR will be performed in up to 12 pts who received ≤5 prior treatment regimens for PROC. In the DDR, TV will be given at previously decided lower doses IV 3Q4W for the same dose intensity as the standard 1Q3W dose; the primary endpoint is incidence of DLTs. In phase 2, pts who received ≤1 prior cytotoxic chemo regimen for PROC will be randomized to receive TV administered as IV 1Q3W or as IV 3Q4W, if shown to be tolerable. The primary endpoint for phase 2 is confirmed ORR by RECIST v1.1. Secondary endpoints include DOR, time to response, DCR, CA-125 response rate by GCIG criteria, PFS, OS, pharmacokinetics, and safety. Clinical trial information: NCT03657043.

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The Value of CA 125 and CA72-4 in Management of Patients with Epithelial Ovarian Cancer

Disease Markers ◽

10.1155/1998/738321 ◽

1998 ◽

Vol 14 (3) ◽

pp. 155-160 ◽

Cited By ~ 16

Author(s):

Salah T. Fayed ◽

Samira M. Ahmad ◽

Samar K. Kassim ◽

Ali Khalifa

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Residual Disease ◽

Ca 125 ◽

Platinum Based Chemotherapy ◽

Pelvic Masses ◽

Radiometric Assay ◽

Normal Women

The role of the tumor markers CA125 and CA72-4 has been evaluated in the diagnosis and management of ovarian cancer. Both markers were measured in 30 patients with proven epithelial ovarian cancer, 30 patients with benign pelvic masses and 30 normal women. CA125 and CA72-4 were measured using the luminometric immunoassay and immuno-radiometric assay respectively. All patients with ovarian cancer were submitted to surgical staging and cytoreduction followed by adjuvant platinum based chemotherapy for 3–6 courses. Fixing the specificity at 95%, CA125 had a sensitivity of 76.7% at a cut-off 85u/ml while CA72-4 had a sensitivity of 70% at a cut-off 8.5 u/ml. The combination of CA72-4 with CA125 increased the sensitivity to 95% while fixing the specificity at 95%. Among seven cases with stage I and II ovarian cancer five cases had CA125 level below 85 U/ml, three patients out of them had CA72-4 above 8.5 U/ml. CA 72-4 could reflect the residual disease following cytoreduction and could improve the detection of relapse by CA125.Conclusion: CA72-4 could complement the standard tumor marker CA125 both in diagnosis and follow up of patients with epithelial ovarian cancer.

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Gemcitabine and Vinorelbine Combination in Platinum-Sensitive Recurrent Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181a8407e ◽

2009 ◽

Vol 19 (9) ◽

pp. 1529-1534 ◽

Cited By ~ 5

Author(s):

Annamaria Ferrero ◽

Vilma Logrippo ◽

Pier Giorgio Spanu ◽

Luca Fuso ◽

Stefania Perotto ◽

...

Keyword(s):

Ovarian Cancer ◽

Response Rate ◽

Response Duration ◽

Recurrent Ovarian Cancer ◽

Ca 125 ◽

Cancer Antigen 125 ◽

Median Response ◽

Platinum Sensitive ◽

Free Interval ◽

Platinum Based Chemotherapy

Objectives:Most patients with ovarian cancer are candidates for second-line or salvage treatments often for prolonged periods. Patients with platinum-sensitive disease can benefit from a platinum retreatment with a likelihood of response dependents on the treatment-free interval. Alternative agents and combination chemotherapy are potential therapeutic approaches. At our institution, we carried out a phase II trial to evaluate feasibility, efficacy, and toxicity of gemcitabine and vinorelbine combination in recurrent ovarian carcinoma. The aim of the present study was to evaluate the role of this combination in patients with platinum-sensitive disease.Patients and Methods:Patients with platinum-sensitive disease recurring after 1 or more lines of platinum-based chemotherapy were included. Vinorelbine at 25 mg/m2followed by gemcitabine at 1000 mg/m2was administered intravenously on days 1 and 8 every 3 weeks. Response Evaluation Criteria in Solid Tumors and cancer antigen 125 test (CA-125 Kinetics [Rustin criteria]) were adopted to classify responses. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria.Results:Thirty-nine patients were eligible. Platinum-free interval (PFI) was 6 to 12 months in 13 patients (33.3%; PFI 6-12) and more than 12 months in 26 patients (66.7%; PFI > 12). The overall response rate was 48.7%, with 6 complete responses. Median response duration was 38 weeks. The response rate was 23% in PFI 6-12 and 62% in PFI >12. The most frequently observed toxicity was hematological, with 23% of the patients having grade 3 or 4 neutropenia.Conclusions:Gemcitabine and vinorelbine combination is effective and well tolerated in recurrent platinum-sensitive ovarian cancer. It may represent an option in the management of these patients because the chronic nature of the disease.

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Evaluation of serial serum IL-6 levels in women with newly diagnosed ovarian cancer on a prospective clinical trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.5065 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 5065-5065 ◽

Cited By ~ 1

Author(s):

J. Mahoney ◽

H. Lee ◽

R. Foster ◽

U. Matulonis ◽

Z. Duan ◽

...

Keyword(s):

Ovarian Cancer ◽

Survival Data ◽

Residual Disease ◽

Sandwich Elisa ◽

Stage Iv ◽

Residual Tumor ◽

Figo Stage ◽

Ca 125 ◽

Platinum Based Chemotherapy ◽

Surgical Debulking

5065 Background: Elevated levels of IL-6 in serum have been reported in patients (pts) with mullerian malignancies (MM) and have been associated with a poor prognosis. Little is know about the behavior of IL-6 during effective cytotoxic therapy and its correlation to various clinical parameters. Methods: Pts with surgically debulked FIGO Stage II, III, and IV MM were enrolled in the Modified Triple Doublets trial. 83 pts were assigned to a cohort in accordance with the extent of surgical debulking. Cohort I included women who had been optimally cytoreduced to <1cm of residual tumor. Cohort II consisted of pts who had either post-debulking residual disease >1cm or stage IV disease. Both cohorts were treated with 3 sequential chemotherapy doublets, gemcitabine/carboplatin, paclitaxel/carboplatin, and adriamycin/topotecan. Each doublet was delivered for 3 cycles. Serum was collected from pts prior to initiating each doublet at cycles 1, 4, 7 and at the end of study (post cycle 9). Serum IL-6 levels were measured in triplicate by sandwich ELISA. Results: Pts with MM had elevated levels of IL-6 following debulking surgery (mean = 12.7 pg/ml) as compared to normal controls (n = 11, mean IL-6 = 1.5 pg/ml, p =.01). While there was no significant correlation between IL-6 levels and stage of disease, the IL-6 serum concentrations did correlate with extent of surgical debulking (p = 0.0182). IL-6 concentrations dropped throughout all cycles of platinum based treatment with post platinum treatment mean concentration of 3.9pg/ml. IL-6 levels did not correlate with outcome of second look operation and there was no statistically significant correlation between IL-6 and CA-125 levels (p = 0.1612). Survival data is still immature with a median follow-up of 34 months, yet elevation of IL-6 levels following surgery demonstrates a trend towards inferior survival. Conclusions: IL-6 levels are elevated in ovarian cancer pts following surgical debulking and correlate with the volume of residual disease following surgical cytoreduction. Values decrease during cytoreductive platinum based chemotherapy although IL-6 was not as predictive of response as was CA-125. Data demonstrates a weak correlation betweenworse survival and elevated IL-6 levels. Supported by the Lana Vento Foundation. No significant financial relationships to disclose.

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Panitumumab in platinum-sensitive epithelial ovarian cancer patients with KRAS wild-type: The PROVE-study, a phase II randomized multicenter study of the North-Eastern German Society of Gynaecologic Oncology.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5558 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5558-5558 ◽

Cited By ~ 3

Author(s):

Radoslav Chekerov ◽

Peter Klare ◽

Petra Krabisch ◽

Jochem Potenberg ◽

Georg Heinrich ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Ca 125 ◽

Wild Type ◽

Skin Reactions ◽

Free Survival ◽

Platinum Sensitive ◽

Platinum Based Chemotherapy

5558 Background: For ovarian cancer (OC) patients with platinum-sensitive recurrence the addition of new biologic agents to chemotherapy may improve survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). The purpose of this trial was to investigate the therapeutic efficacy of panitumumab in the combination with carboplatin-based chemotherapy in relation to the respective standard combination in patients with a KRAS wildtype with platinum-sensitive recurrent ovarian cancer (NCT01388621). Methods: Major eligibility criteria were pretreated platinum-sensitive epithelial ovarian/ fallopian/ peritoneal cancer and no more than 2 prior treatments for this disease. Only patients with measurable disease or elevated CA125 and with KRAS wild type were eligible. Patients were treated with Carboplatin AUC4/Gemcitabine 1000 mg/m² or Carboplatin AUC5/PLD 40 mg/m² and randomized to panitumumab 6 mg/kg day 1 and day 15, every 3 or 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CT-scan and CA-125 criteria. Results: In this multi-institutional phase II trial 102 patients were randomized and 96 enrolled for the final analysis. Progression-free survival in the intention-to-treat population (N=96) was 9.5 vs. 10.7 months (HR 0.829, 95%CI of 8.5-11.6 months vs 8.5-13.1 months) for the experimental vs. standard arm, p=0.45. Data of overall survival are not jet evaluable. The most common treatment related grade 3+ toxicities included hematologic toxicity (54%), skin reactions (18%) and gastrointestinal events (16%). Conclusions: The addition of panitumumab to platinum-based chemotherapy for recurrent ovarian cancer does not influence efficacy and progression-free survival in platinum sensitive patients, while no new additional toxicity aspects for panitumumab were evaluated. Clinical trial information: NCT01388621.

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Early-Stage Ovarian Malignancy Score versus Risk of Malignancy Indices: Accuracy and Clinical Utility for Preoperative Diagnosis of Women with Adnexal Masses

Medicina ◽

10.3390/medicina56120702 ◽

2020 ◽

Vol 56 (12) ◽

pp. 702

Author(s):

Phichayut Phinyo ◽

Jayanton Patumanond ◽

Panprapha Saenrungmuaeng ◽

Watcharin Chirdchim ◽

Tanyong Pipanmekaporn ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Utility ◽

Early Stage ◽

Ca 125 ◽

Lower Sensitivity ◽

Ovarian Malignancy ◽

Threshold Probability ◽

Adnexal Masses ◽

Risk Of Malignancy ◽

Early Stage Ovarian Cancer

Background and objectives: To compare the diagnostic accuracy and clinical utility of the Early-stage Ovarian Malignancy (EOM) score with the Risk of Malignancy Index (RMI) in the presurgical assessment of women presenting with adnexal masses. Materials and Methods: A secondary analysis was carried out in a retrospective cohort of women who presented with an adnexal mass and were scheduled for surgery at Phrapokklao Hospital between September 2013 and December 2017. The clinical characteristics, ultrasonographic features of the masses, and preoperative CA-125 levels were recorded. The EOM and the RMI score were calculated and compared in terms of accuracy and clinical utility. Decision curve analysis (DCA), which examined the net benefit (NB) of applying the EOM and the RMI in practice at a range of threshold probabilities, was presented. Results: In this study, data from 270 patients were analyzed. Fifty-four (20.0%) women in the sample had early-stage ovarian cancer. All four RMI versions demonstrated a lower sensitivity for the detection of patients with early-stage ovarian cancer compared to an EOM score ≥ 15. An EOM ≥ 15 resulted in a higher proportion of net true positive or NB than all versions of the RMIs from a threshold probability of 5% to 30%. Conclusions: It also showed a higher capability to reduce the number of inappropriate referrals than the RMIs at a threshold probability between 5% and 30%. The EOM score showed higher diagnostic sensitivity and has the potential to be clinically more useful than the RMIs to triage women who present with adnexal masses for referral to oncologic gynecologists. Further external validation is required to support our findings.

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