Sorafenib in Combination With Gemcitabine in Recurrent Epithelial Ovarian Cancer: A Study of the Princess Margaret Hospital Phase II Consortium

2010 ◽  
Vol 20 (5) ◽  
pp. 787-793 ◽  
Author(s):  
Stephen A. Welch ◽  
Hal W. Hirte ◽  
Laurie Elit ◽  
Russel J. Schilder ◽  
Lisa Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Stable Disease ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Ca 125 ◽  
Response Evaluation ◽  
Time To Progression ◽  
Response Evaluation Criteria

Objectives:Antiangiogenic strategies have demonstrated efficacy in epithelial ovarian cancer (EOC). Sorafenib is a novel multitargeted kinase inhibitor with antiangiogenic activity. Gemcitabine has known activity against EOC. A phase 1 clinical trial of this combination suggested activity in ovarian cancer with no dose-limiting toxicity. This phase 2 study was designed to examine the safety and efficacy of gemcitabine and sorafenib in patients with recurrent EOC.Methods:Patients with recurrent EOC after platinum-based chemotherapy and who had subsequently received up to 3 prior chemotherapy regimens were eligible. Gemcitabine (1000 mg/m2 intravenous [IV]) was administered weekly for 7 of 8 weeks in the first cycle, then weekly for 3 weeks of each subsequent 4-week cycle. Sorafenib (400 mg p.o. bid) was given continuously. The primary end point for this trial was objective response rate by the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included Gynecologic Cancer Intergroup (GCIG) CA-125 response, time to progression, overall survival, and toxicity.Results:Forty-three patients were enrolled, and 33 completed at least 1 cycle. Two patients had a partial response (Response Evaluation Criteria in Solid Tumors objective response rate = 4.7%). Ten patients (23.3%) maintained response or stable disease for at least 6 months. GCIG CA-125 response was 27.9%. The median time to progression was 5.4 months, and the median overall survival was 13.0 months. Hematologic toxicity was common but manageable. The most common nonhematologic adverse events were hand-foot syndrome, fatigue, hypokalemia, and diarrhea.Conclusion:This trial of gemcitabine and sorafenib in recurrent EOC did not meet its primary efficacy end point, but the combination was associated with encouraging rates of prolonged stable disease and CA-125 response.

Trabectedin for Women With Ovarian Carcinoma After Treatment With Platinum and Taxanes Fails

2005 ◽  
Vol 23 (9) ◽  
pp. 1867-1874 ◽  
Author(s):  
Cristiana Sessa ◽  
Filippo De Braud ◽  
Antonella Perotti ◽  
Jean Bauer ◽  
Giuseppe Curigliano ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Advanced Ovarian Cancer ◽  
Treatment Interruption ◽  
Response Evaluation ◽  
Time To Progression ◽  
Platinum Sensitive

Purpose To assess the efficacy and toxicity of the marine-derived alkaloid trabectedin (ET-743) in patients with advanced ovarian cancer refractory to or experiencing disease relapse after platinum- and taxane-based chemotherapy. Patients and Methods Fifty-nine patients from four institutions either resistant (n = 30) or sensitive (n = 29) to prior platinum and taxanes were treated with a 3-hour infusion of trabectedin every 3 weeks. Patients were monitored weekly for toxicity and restaged every two cycles for response. Response was assessed according to Response Evaluation Criteria in Solid Tumors Group. Results The peer-reviewed objective response rate in platinum-sensitive patients was 43% (95% CI, 23% to 65%) with an estimated median time to progression of 7.9 months (95% CI, 7.5 to 14.1 months); in platinum-resistant patients two partial responses were observed. Responses were durable for up to 12.9 months (median, 5 months). The predominant toxicities at the recommended dose of 1,300 μg/m2 were neutropenia, asthenia, and self-limited increase of aminotransferases never requiring treatment interruption. Conclusion Trabectedin administered as a 3-hour infusion at 1,300 μg/m2 is a safe new drug with promising activity in relapsed ovarian cancer, showing a 43% objective response rate in patients with platinum-sensitive disease, which favorably compares with other salvage treatments and warrants additional development either alone or in combination.

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.

Veliparib Monotherapy to Patients With BRCA Germ Line Mutation and Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer: A Phase I/II Study

2017 ◽  
Vol 27 (9) ◽  
pp. 1842-1849 ◽  
Author(s):  
Karina Dahl Steffensen ◽  
Parvin Adimi ◽  
Anders Jakobsen
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Phase I ◽  
Evaluation Criteria ◽  
Ca 125 ◽  
Response Evaluation ◽  
Polymerase Inhibitors ◽  
Platinum Resistant ◽  
Response Evaluation Criteria ◽  
Sensitive Relapse

ObjectiveA new treatment principle, which seems to radically change the treatment approach in ovarian cancer (OC), has developed over the past few years. Poly(ADP-ribose) polymerase inhibitors work by interfering with mechanisms important to DNA damage repair. Cancer cells that already have defects in the BRCA genes are particularly sensitive to treatment with poly(ADP-ribose) polymerase inhibitors. The main purpose of this study was to investigate the effect of veliparib in patients with known BRCA1/2 mutations and with a platinum-resistant or intermediate sensitive relapse of OC.MethodsMajor eligibility criteria were primary epithelial ovarian/fallopian/peritoneal cancer patients with a platinum-resistant or intermediate sensitive relapse of OC and with evaluable disease by either Response Evaluation Criteria In Solid Tumors or Gynecological Cancer Intergroup CA-125 criteria. Patients were treated with oral veliparib twice daily on days 1 to 28.ResultsSixteen patients were enrolled in the phase I part, and a maximum tolerable dose of 300 mg twice daily was established. The phase II part enrolled 32 patients with a median of 4 previous treatment regimens. The overall response rate combining Response Evaluation Criteria In Solid Tumors and CA-125 response was 65% (6% complete response and 59% partial response). Progression-free and overall survival rates of the intention-to-treat population were 5.6 months (95% confidence interval, 5.2–7.3 months) and 13.7 months (95% confidence interval, 10.2–17.3 months), respectively. The most common phase II treatment-related grade 2 toxicities included fatigue (22%), nausea (22%), and vomiting (9%).ConclusionsTreatment with veliparib in heavily pretreated patients with relapse of OC demonstrates a considerable efficacy with an acceptable toxicity profile.

Palliative treatment with electrochemotherapy in recurrent or metastatic vaginal cancer

2020 ◽  
Vol 30 (7) ◽  
pp. 939-946 ◽  
Author(s):  
Anna Myriam Perrone ◽  
Martina Ferioli ◽  
Andrea Galuppi ◽  
Manuela Coe ◽  
Francesca De Terlizzi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Partial Response ◽  
Stable Disease ◽  
Palliative Treatment ◽  
Progressive Disease ◽  
Evaluation Criteria ◽  
Complete Response ◽  
Vaginal Cancer ◽  
Response Evaluation ◽  
Response Evaluation Criteria

ObjectiveVaginal metastases are very rare events with a poor prognosis. To improve the quality of life, local treatments should be considered. The aim of this study was to evaluate the role of electrochemotherapy as palliative treatment in vaginal cancer not amenable to standard treatments due to poor performance status, previous treatments, or advanced disease.MethodsThis is a prospective observational study on patients diagnosed with vaginal cancer and treated from January 2017 to December 2018 with palliative electrochemotherapy. We collected data on patients with vaginal cancer treated by electrochemotherapy with the aim of local control. Data regarding electrochemotherapy, hospital stay, adverse events, and patient outcomes were analyzed. Intravenous bleomycin was injected as a bolus in 2–3 min at a dose of 15 000 UI/m2 and electrical pulses started 8 min after chemotherapy. Electrochemotherapy response was defined according to the Response Evaluation Criteria in Solid Tumors.ResultsFive patients with vaginal recurrence (two squamous, two melanomas, and one leiomyosarcoma) and one with vaginal metastasis from intestinal adenocarcinoma received one treatment and two patients were re-treated. Imaging reported nodal metastasis (inguinal or pelvic) in two patients, distant metastases in two, and both node and distant metastasis in two patients, respectively. Response Evaluation Criteria in Solid Tumors showed a complete response in one patient, partial response in three patients, stable disease in one patient, and progressive disease in one patient, with an overall response rate of 67% and a clinical benefit rate (complete response, partial response, stable disease) of 83%. Two patients were re-treated and had a new response (partial response and stable disease, respectively). At last follow-up, two patients had died of the disease, two were alive with stable disease, one was alive with progressive disease, and one was alive without disease. Median post-electrochemotherapy overall survival was 12.9 months (range 1.6–26.9) and 1-year overall survival was 66.7%.ConclusionsThis preliminary experience showed a tumor response or stabilization in 83% of patients requiring palliative management for vaginal cancer. Further studies are needed to evaluate treatment outcome in larger and prospective series.

Chemosaturation durch perkutane hepatische Perfusion mit Melphalan bei hepatisch metastasiertem Aderhautmelanom: eine Überlebens- und Sicherheitsanalyse

2021 ◽  
Vol 42 (08) ◽  
pp. 576-584
Author(s):  
Cornelia Lieselotte Angelika Dewald ◽  
Jan B. Hinrichs ◽  
Lena Sophie Becker ◽  
Sabine Maschke ◽  
Timo C. Meine ◽  
...  
Keyword(s):  
Disease Control ◽  
Solid Tumors ◽  
Overall Response Rate ◽  
Response Rate ◽  
Evaluation Criteria ◽  
Progressionsfreies Überleben ◽  
Response Evaluation ◽  
Ischämischer Insult ◽  
Kaplan Meier ◽  
Response Evaluation Criteria

Ziel Die Chemosaturation mittels perkutaner hepatischer Perfusion mit Melphalan (CS-PHP) ist ein palliatives Therapieverfahren für Patienten mit nicht kurativ behandelbaren Lebertumoren. Die CS-PHP erlaubt eine selektive intrahepatische Anreicherung von hochdosiertem Melphalan bei minimaler systemischer Toxizität durch venöse Hämofiltration. Ziel dieser Studie war es, das Ansprechen und Überleben sowie die Sicherheit der CS-PHP-Prozedur bei Patienten mit leberdominant metastasiertem Aderhautmelanom zu evaluieren. Material und Methoden Gesamtansprechrate (overall response rate, ORR) und Krankheitskontrollrate (disease control rate, DCR) wurden anhand von Response Evaluation Criteria In Solid Tumors (RECIST1.1) ermittelt. Medianes Gesamtüberleben (mOS), medianes progressionsfreies Überleben (mPFS) und hepatisches mPFS (mhPFS) wurden mittels Kaplan-Meier-Schätzer ermittelt. Nebenwirkungen wurden entsprechend der einheitlichen Terminologie-Kriterien für Nebenwirkungen (CTCAE) v5 klassifiziert. Ergebnisse 30 Patienten wurden zwischen Oktober 2014 und Januar 2019 mit 70 Chemosaturationen behandelt. Die ORR betrug 42,3 % und die DCR 80,8 %. Das mOS betrug 12 (95 %-Konfidenzintervall (KI) 7–15) Monate, das mPFS 6 (95 %-KI 4–10) und das mhPFS ebenfalls 6 (95 %-KI 4–13) Monate. Signifikante, aber transiente hämatotoxische Nebenwirkungen waren häufig (87 % Grad-3/4-Thrombozytopenie), hepatische Toxizität bis Leberversagen (n = 1/70) sowie kardiovaskuläre Komplikationen (ischämischer Insult, n = 1/70) waren selten. Schlussfolgerung Das palliative Therapiekonzept der Chemosaturation ist bei Patienten mit hepatisch metastasiertem Aderhautmelanom effektiv. Die interventionelle Prozedur ist sicher, seltene, aber schwerwiegende kardiovaskuläre und hepatische Komplikationen erfordern eine sorgfältige Patientenselektion und intensive Aufmerksamkeit.

The evolving landscape of criteria for evaluating tumor response in the era of cancer immunotherapy: From Karnofsky to iRECIST

2018 ◽  
Vol 104 (2) ◽  
pp. 88-95 ◽  
Author(s):  
Alessandro Inno ◽  
Giuseppe Lo Russo ◽  
Matteo Salgarello ◽  
Giulia Corrao ◽  
Raffaella Casolino ◽  
...  
Keyword(s):  
Tumor Response ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Therapy Response ◽  
Clinical Activity ◽  
Special Focus ◽  
Response Evaluation ◽  
Recist 1.1 ◽  
New Anticancer Drugs ◽  
Response Evaluation Criteria

The objective response is an important endpoint to evaluate clinical activity of new anticancer drugs. Standardized criteria for evaluating response are needed for comparing results of different trials and represent the basis for advances in cancer therapy. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 are the most used in clinical practice and in clinical trials; however, they are not able to capture atypical responses seen with immunotherapy drugs. We describe the evolution of response criteria with a special focus on the immune-related criteria.

scholarly journals Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1272 ◽  
Author(s):  
Laura Marconato ◽  
Silvia Sabattini ◽  
Giorgia Marisi ◽  
Federica Rossi ◽  
Vito Ferdinando Leone ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Safety Profile ◽  
Median Overall Survival ◽  
Response Rate ◽  
Treatment Options ◽  
Objective Response ◽  
Metronomic Chemotherapy ◽  
Time To Progression ◽  
Activity Data

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.

scholarly journals Evaluation of the Optimal Number of Lesions Needed for Tumor Evaluation Using the Response Evaluation Criteria in Solid Tumors: A North Central Cancer Treatment Group Investigation

2009 ◽  
Vol 27 (19) ◽  
pp. 3205-3210 ◽  
Author(s):  
Shauna L. Hillman ◽  
Ming-Wen An ◽  
Michael J. O'Connell ◽  
Richard M. Goldberg ◽  
Paul Schaefer ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cancer Treatment ◽  
Solid Tumors ◽  
Overall Response Rate ◽  
Response Rate ◽  
Evaluation Criteria ◽  
Response Evaluation ◽  
North Central ◽  
Overall Response ◽  
Response Evaluation Criteria

Purpose In February 2000, the criteria for measuring tumor shrinkage as an indicator of antitumor activity were redefined by the Response Evaluation Criteria in Solid Tumors (RECIST). This resulted in simplifying bidimensional to unidimensional measurement of lesions. Under RECIST, all lesions, up to 10, must be measured. Scanning and measuring multiple lesions is costly, time-consuming, and a disincentive to participation in clinical trials. We investigated whether fewer than 10 lesions can be measured without compromising the accuracy of assessing a regimen's activity. Patients and Methods Thirty-two North Central Cancer Treatment Group trials including 2,374 patients were analyzed. Twelve studies were conducted before RECIST; 20 were conducted post-RECIST. Agreement between objective status by cycle, confirmed response, overall response rate, and time to progression (TTP) was evaluated based on all 10 versus the largest one through five lesions. Results The median number of lesions reported on RECIST trials did not differ from pre-RECIST trials (median = 2.0). One lesion at baseline was reported in 49% of patients, two lesions in 28% of patients, three lesions in 12% of patients, four lesions in 6% of patients, and five lesions in 5% of patients in post-RECIST trials. Utilizing the largest two lesions produced excellent concordance with that using all lesions for all end points. In no trial did the overall response rate differ by more than 3% when two versus all lesions were considered. Evaluating more than two lesions did not significantly improve agreement. Conclusion Based on these trials, the assessment of more than two lesions did not alter the conclusions regarding a treatment's efficacy as judged by response rate or TTP.

scholarly journals Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252665
Author(s):  
Christine S. Walsh ◽  
Mitchell Kamrava ◽  
Andre Rogatko ◽  
Sungjin Kim ◽  
Andrew Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Interim Analysis ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Time To Progression ◽  
Free Survival ◽  
Platinum Resistant ◽  
Duration Of Response

Objective To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer. Methods Patients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3–6 and as maintenance monotherapy in cycles 7–34. Palliative radiation to a non-target symptomatic lesion was allowed. The primary objective was overall response rate by RECIST 1.1 criteria. Secondary objectives included safety, progression-free survival, time to progression, duration of response and overall survival. Results An interim analysis for futility was performed at 18 evaluable patients. Overall response rate was 60%, duration of response was 4.9 months and time to progression was 5.2 months. Progression-free survival at 6 and 12 months was 43% and 5%. Median progression-free survival was 6.2 months and median overall survival was 11.3 months. In all patients, CA125 levels reflected response and progression. There were no pseudoprogression events. After receiving palliative radiation during pembrolizumab maintenance, a patient with recurrent ovarian clear cell carcinoma had an exceptional and durable response that is ongoing for greater than 2 years. After consultation with the sponsor, based on the modest duration of response observed at the interim analysis for futility, the decision was made to close the trial to further accrual. Conclusions The addition of pembrolizumab to cisplatin and gemcitabine did not appear to provide benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer.

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