Efficacy of platinum-based chemotherapy in platinum-resistant ovarian cancer: A systematic review with pooled analysis of outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18076-e18076
Author(s):  
Alexey Rumyantsev ◽  
Alexandra Tyulyandina ◽  
Mikhail Fedyanin ◽  
Ilya Pokataev ◽  
Elena Glazkova ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Linear Regression ◽  
Multiple Linear Regression ◽  
Objective Response ◽  
Pooled Analysis ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Platinum Chemotherapy ◽  
Platinum Agents

e18076 Background: Current management of recurrent ovarian cancer (OC) is based on the amount of time between the completion of penultimate platinum-based treatment and the detection of relapse. Patients with platinum-free interval (PFI) < 6 mo. are considered to be platinum-resistant (PROC) and to have low response rate (RR) probability to platinum-based chemotherapy. Methods: We searched PubMed database for all prospective and retrospective full-text articles and abstracts on the treatment of patients with PROC for all years between 01/01/2000 and 01/06/2019 in English language. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) tool was used to ensure transparent reporting of the results. Study inclusion criteria were: 1) morphologically confirmed epithelial ovarian cancer; 2) standard definition of PROC as a disease that recurred within 6 months after completion of platinum-based chemotherapy; 3) treatment with platinum- or non-platinum chemotherapy with agents that are routinely used for OC; 4) no concomitant therapy with targeted or investigational agents; 5) clearly defined RR for patients with PROC and criteria used for response assessment. Pooled analysis of outcomes and multiple linear regression analysis was conducted to assess the impact of platinum salts on probability of response. Results: We identified 7156 articles and screened them for title and abstract. After the review process we selected 197 studies for further analysis. Of them, 52 (n = 1320) and 145 (n = 6937) trials assessed efficacy of platinum- and non-platinum based chemotherapy respectively. Among patients treated with platinum-based and non-platinum chemotherapy RR was 36.04% (95% CI 33.45-38.63) and 14.85% (95% CI 14.01-15.68) respectively. Pooled median progression-free survival was 5.8 mo. and 3.75 mo. respectively. In multiple linear regression model administration of platinum-based chemotherapy was the strongest predictor of objective response with B value 0.503 (p < 0.001). Among platinum agents cisplatin (RR 39.9%: 95% CI 35.8-44.0%) and carboplatin (RR 42.3%; 95% CI 37.0-47.6%) were associated with better rates of objective response compared to oxaliplatin (RR 28.1%; 95% CI 23.9-32.3). Conclusions: This systematic review shows that patients with 'platinum-resistant' ovarian carcinoma may derive significant benefit from reintroduction of platinum agents and their value should be evaluated in further randomized trials.

scholarly journals 831P Efficacy of platinum-based chemotherapy in platinum-resistant ovarian cancer: A systematic review with pooled analysis of outcomes

2020 ◽  
Vol 31 ◽  
pp. S625-S626
Author(s):  
A. Rumyantsev ◽  
A. Tyulyandina ◽  
M. Fedyanin ◽  
I. Pokataev ◽  
E. Glazkova ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Pooled Analysis ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy

scholarly journals Predictive Value of HE4 in Platinum-Based Chemotherapy for Ovarian Cancer: A Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Yue Han ◽  
Lili Jiang ◽  
Kuiran Liu ◽  
Ling Ouyang ◽  
Yan Li
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Sensitivity And Specificity ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Diagnostic Odds Ratio ◽  
The Third ◽  
Preoperative Serum ◽  
Platinum Based Chemotherapy ◽  
Platinum Chemotherapy

ObjectiveTo evaluate the value of serum Human epididymis protein 4 (HE4) for predicting the resistance of ovarian cancer (OS) to platinum chemotherapy.MethodWe searched the MEDLINE (PubMed), EMBASE, Cochrane Central, Web of Science, SCOPUS, and CNKI databases and screened all studies evaluating serum HE4 for predicting OC resistance to treatment with platinum. Two researchers independently evaluated the quality of all eligible original studies using QUADAS-2. RevMan 5.4 was used to compile the quality evaluation form. We also performed a meta-analysis with STATA15.1, and Deek’s funnel plots were used to detect any publication bias.ResultsEight studies were included in the final meta-analysis. Our results showed that the sensitivity and specificity of preoperative serum HE4 in predicting the resistance of OC to platinum chemotherapy was 80% and 67%, respectively. The diagnostic odds ratio was 8, and the AUC was 0.78 (95% CI: 0.75-0.82), whereas the pooled sensitivity and specificity of serum HE4 after the third-cycle of chemotherapies for predicting chemoresistance in OC was 86% and 85%, respectively, with a diagnostic odds ratio of 33 and AUC = 0.92 (95% CI: 0.89 – 0.94).ConclusionHE4 may be an effective predictor of platinum-based chemotherapeutic resistance of OC. Serum HE4 levels after the third chemotherapy cycle may be indicative for clinical practice. Further research is needed to validate the significance of HE4 in the long-term management of OC.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021220099).

Cediranib in combination with olaparib in patients without a germline BRCA1/2 mutation with recurrent platinum-resistant ovarian cancer: Phase IIb CONCERTO trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6056-6056
Author(s):  
Jung-min Lee ◽  
Richard G. Moore ◽  
Sharad A. Ghamande ◽  
Min S. Park ◽  
John Paul Diaz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Response Rate ◽  
Brca Mutation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Repair Gene ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy

6056 Background: A Phase I trial (NCT01116648) of cediranib (cedi) in combination with olaparib (ola) (cedi + ola) demonstrated an overall response rate of 44% in patients (pts) with recurrent ovarian cancer (OC), including pts without a deleterious or suspected deleterious gBRCAm (non-gBRCAm; Liu et al. Eur J Cancer 2013). The subsequent Phase II trial (NCT01116648) showed significant improvement in progression-free survival (PFS) with cedi + ola versus ola monotherapy in recurrent platinum-sensitive OC pts, notably in non-gBRCAm pts (Liu et al. Lancet Oncol 2014). We report data from the Phase IIb, single-arm, open-label CONCERTO study investigating cedi + ola in non-gBRCAm pts with recurrent platinum-resistant OC who had received ≥3 previous lines of therapy for advanced OC (NCT02889900). Methods: Pts with disease progression <6 months from the last receipt of platinum-based chemotherapy received cedi tablets (30 mg once daily) plus ola tablets (200 mg twice daily) until progression or unacceptable toxicity. gBRCAm pts were ineligible. Primary endpoint: objective response rate (ORR) by independent central review (ICR; RECIST 1.1). Key secondary endpoints: PFS and safety. Results: 60 pts from the USA were included (median age: 64.5 years; median number of previous systemic treatment regimens: 4 [range: 2–9]; previous bevacizumab: 53). All pts had high-grade OC (90% serous; 3.3% clear cell; 3.3% endometrioid; 3.3% other). 7% of pts had tumor BRCA2 (confirmed somatic) mutations, 80% of pts had no tumor BRCA mutation (non-tBRCAm) and 13% of pts were not evaluable for tBRCAm. Five (8%) pts who were non-tBRCAm carried somatic homologous recombination repair gene mutations (FoundationOne Clinical Trial Assay, Foundation Medicine, Inc). The Table shows results of key endpoints. Most common grade ≥3 adverse events (AEs) that occurred in pts were hypertension (30%), fatigue (22%) and diarrhea (13%). 37% of pts reported serious AEs, of which nausea (7%) was most common. Dose interruptions, reductions and discontinuations were caused by AEs in 55%, 18% and 18% of pts, respectively, who received cedi + ola. Conclusions: Cedi + ola showed evidence of antitumor activity in heavily pretreated non-gBRCAm pts with recurrent platinum-resistant OC. Toxicity was manageable with dose modifications. Clinical trial information: NCT02889900. [Table: see text]

Systematic review of adjuvant therapy for early stage (epithelial) ovarian cancer

2003 ◽  
Vol 13 (4) ◽  
pp. 395-404 ◽  
Author(s):  
B. Winter-Roach ◽  
L. Hooper ◽  
H. Kitchener
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Early Stage ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Difference ◽  
Well Differentiated ◽  
Platinum Chemotherapy

A systematic review and meta analysis has been undertaken in order to evaluate the effectiveness of adjuvant therapy following surgery for early ovarian cancer. Trials reported since 1990 have been of a higher quality enabling a meta analysis of adjuvant chemotherapy vs adjuvant radiotherapy and a meta analysis of adjuvant chemotherapy vs observation. There was no significant difference between radiotherapy and chemotherapy, though these comprised studies which demonstrated considerable heterogeneity. Chemotherapy did confer significant benefit over observation in terms of both overall and disease free survival. Except for women in whom adequate surgical staging has revealed well differentiated disease confined to one or both ovaries with intact capsule, platinum chemotherapy should be offered to reduce risk of recurrence.

PALB2 mutation as a predictive biomarker for immunotherapy in patients with advanced melanoma: Results from (a pooled analysis of) five multicenter, randomized clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21537-e21537
Author(s):  
Changxuan You ◽  
Yating Zheng ◽  
Mengli Huang
Keyword(s):  
Randomized Clinical Trials ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Pooled Analysis ◽  
Advanced Melanoma ◽  
Inhibitor Therapy ◽  
Study Cohort ◽  
Platinum Based Chemotherapy ◽  
Palb2 Mutation ◽  
Inhibitor Treatment

e21537 Background: PALB2, a gene in the homologous recombination repair (HRR) pathway, has been shown to be associated with the efficacy of platinum based chemotherapy, and PARP inhibitor therapy in breast, prostate, ovarian, and pancreatic cancers. However, their predictive value of PALB2 remained unknown in patients with advanced melanoma. Methods: Five independent cohorts (Miao2018, Samstein2018, Allen 2015, Hugo2016, and Synder2014. study cohort) with data from 672 patients with advanced melanoma were used to analyze the correlation with immunogenic marker, and the prognostic effect of PALB2 on immunotherapy. Results: A pooled analysis of five independent cohorts of 672 advanced patients melanoma show that 31 (4.6%) harbored PALB2 mutation ( PALB2mut). PALB2mut (72.63Muts/Mb) was associated with higher tumor mutation burden (TMB) (P < 0.001) than PALB wild-type ( PALB2wt) (19.71Muts/Mb). The same phenomenon has also been observed in TNB, PALB2mut (1983 counts) was associated with higher tumor neoantigen burden (TNB) than PALB2wt (603.5 counts) (P = 0.0147). The objective response rate (ORR) of immunotherapy was 53.33% for the patients with PALB2mut and 24% for the PALB2wt subgroup (P = 0.027). The PALB2mut patients had significantly improved median overall survival (mOS) than the PALB2wt group (Not reach versus 29 months, hazard ratio (HR) = 0.38, 95%CI 0.19−0.73, P = 0.003). A subgroup analysis of CTLA4 inhibitor treatment found that PALB2mut was associated with better ORR (50% versus 18.3%, P = 0.016) on immunotherapy, and mOS in the PALB2mut group was significantly better than that in the PALB2wt group (Not reach versus 21 months, HR = 0.3, 95%CI 0.13−0.68, P = 0.002). However, in the subgroup receiving PD-L1 inhibitor treatment, no ORR benefit was found in the PALB2mut group (66.67% versus 56.76%, P = 1), and there was no difference on mOS between PALB2mut and PALB2wt (Not reach versus 31 months, HR = 0.45, 95%CI 0.11−1.8, P = 0.254). Conclusions: PALB2 mutations was associated with a higher TMB and TNB level. PALB2 may serve as a positive predictor of immunotherapy (CTLA4 inhibitor therapy) in patients with advanced melanoma and their clinical value warrants further investigation.

Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5599-TPS5599
Author(s):  
Rebecca Christian Arend ◽  
Bradley J. Monk ◽  
Thomas J. Herzog ◽  
Jonathan A. Ledermann ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Ca 125 ◽  
Recist 1.1 ◽  
Platinum Resistant ◽  
Phase Iii Study

TPS5599 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.

Activity and Pharmacodynamics of 21-Day Topotecan Infusion in Patients With Ovarian Cancer Previously Treated With Platinum-Based Chemotherapy

1999 ◽  
Vol 17 (8) ◽  
pp. 2553-2553 ◽  
Author(s):  
Howard Hochster ◽  
Scott Wadler ◽  
Carolyn Runowicz ◽  
Leonard Liebes ◽  
Henry Cohen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mononuclear Cells ◽  
Response Rate ◽  
Objective Response ◽  
Ca 125 ◽  
Blood Levels ◽  
Time To Progression ◽  
Peripheral Blood Mononuclear ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

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.

scholarly journals Atezolizumab in locally advanced or metastatic urothelial cancer: a pooled analysis from the Spanish patients of the IMvigor 210 cohort 2 and 211 studies

2020 ◽  
Author(s):  
M. Sotelo ◽  
T. Alonso-Gordoa ◽  
P. Gajate ◽  
E. Gallardo ◽  
R. Morales-Barrera ◽  
...  
Keyword(s):  
Median Duration ◽  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Pooled Analysis ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Geographical Regions ◽  
Duration Of Response

Abstract Background The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. Materials and methods We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. Results Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. Conclusion Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.

A phase I study of pemetrexed (P) plus gemcitabine (G) in relapsed ovarian cancer (OC): Dosing results and evidence of activity

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5083-5083 ◽  
Author(s):  
M. L. Hensley ◽  
F. Derosa ◽  
S. R. Gerst ◽  
P. Sabbatini ◽  
J. Dupont ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Objective Response ◽  
Median Number ◽  
Vitamin Supplementation ◽  
Ovarian Cancer Cells ◽  
Resistant Disease ◽  
Platinum Resistant ◽  
Best Response ◽  
Adequate Organ Function ◽  
Q 14

5083 Background: High expression of folate receptors on ovarian cancer cells may provide excellent targets for P. Preclinical data support synergism with G. Optimal doses of q 14 day P+G with vitamin support in pre-treated OC pts are not known. We sought to determine the maximally tolerated doses (MTD) and to assess for toxicity and activity in relapsed OC. Methods: Pts with relapsed OC, no prior P or G, KPS ≥ 70, and adequate organ function were eligible. Pts were enrolled in cohorts of 3, expanding to 6 if dose-limiting toxicity (DLT) was observed during the first 4 cycles. Pts received P at 300 (cohort 1) or 400 (cohort 2) or 500 (cohort 3) or 600 (cohort 4) mg/m2 followed by G 1500 mg/m2 q 14 d without GCSF. B12 and folic acid were given 1 week prior and continued throughout. DLT was defined as grade (gr) 4 neutropenia (ANC) lasting >7d or neutropenic fever (NF); gr 4 thrombocytopenia or gr 3 with bleeding; ≥gr 3 nonhematologic toxicity, except ALT, AST, alopecia, fatigue; treatment delay ≥1 week due to any unresolved toxicity. Response assessed by RECIST. Results: 16 pts (median age 55, range 43–75; median number prior cytotoxic regimens 2, range 1–4) have enrolled in 4 cohorts. 15 are evaluable for response (1 treated after resection of recurrence); 13 of these15 had a platinum-free interval <6 months. 1 pt in cohort 1 had global deterioration during cycle 1 and was replaced, with best response counted as progressive disease (PD). 1 pt in cohort 3 had dose delay ≥1 week, meeting DLT criteria. Cohort 3 was expanded to 6 pts with no further DLT. 3 pts enrolled in cohort 4 with no DLTs observed. Toxicities per cycle (n = 108): gr 3 ANC 31%; gr 4 ANC 27%; gr 3 dehydration 0.9%; gr 3 platelets 0.9%; 0 pts had NF. Median # cycles/pt was 6, range 1–16, median cycle length 14 d. Objective response was observed in 27% (4/15 pts: 4 PR; 7 SD; 4 PD). All 4 responses were among pts with platinum resistant disease. >50% decrease in CA125 for more than two measurements was observed in 9/15 (60%) pts with evaluable CA125s. Median time to progression is 15 wks (95% confidence interval 10–32 wks). Conclusions: MTD is not yet reached. P 500 mg/m2 + G 1500 mg/m2 with vitamin supplementation is safe in pts with previously treated OC. 27% of patients with platinum-resistant disease had objective responses. [Table: see text]

Phase II study of DMXAA combined with carboplatin and paclitaxel in recurrent ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5032-5032 ◽  
Author(s):  
H. Gabra
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
Figo Stage ◽  
Vascular Disrupting Agent ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

5032 Background: DMXAA (AS1404) is a small-molecule vascular disrupting agent, which in animal models shows additive or supra-additive effects with cytotoxics, including taxanes and platinum agents. This phase II study evaluated DMXAA in combination with carboplatin and paclitaxel in recurrent platinum-sensitive ovarian cancer patients with a progression-free interval of more than 6 months after response to platinum-based chemotherapy. Methods: Patients had first diagnosed disease FIGO stage Ic-IV, with presence of recurrent disease confirmed by imaging. Patients were randomised 1:1 to receive up to 6 cycles of carboplatin (AUC 6 mg/ml × min) and paclitaxel (175 mg/m2) with or without DMXAA (1200 mg/m2). Safety assessments included EKG, adverse events, laboratory screens and ophthalmic exam. Efficacy endpoints are objective response rates, time to progression, duration of response and stable disease, and median and 1-year survival. Results: 55 patients have been enrolled to date from a planned total of ∼70. Initial safety findings in the two arms are comparable. Preliminary investigator-assessed RECIST response data show the following unconfirmed outcomes: of 17 patients in the DMXAA arm, there are 10 with partial responses (PRs), 7 with stable disease (SD) and 0 with progressive disease (PD); of 14 patients in the control arm, there are 8 PRs, 6 SDs and 0 PDs. Conclusions: Initial safety findings suggest that addition of DMXAA to standard doses of carboplatin and paclitaxel did not add significantly to toxicity. Efficacy assessments are ongoing to determine the value of the triple combination in recurrent ovarian cancer. No significant financial relationships to disclose.

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