Đánh giá kết quả điều trị bệnh nhân ung thư biểu mô buồng trứng tái phát bằng phác đồ paclitaxel tại Bệnh viện K

Author(s):  
Thi Lan Nguyen

TÓM TẮT Đặt vấn đề: Ung thư biểu mô buồng trứng (UTBMBT) là bệnh ác tính của tế bào biểu mô buồng trứng. Bệnh có tiên lượng xấu. Mặc dù điều trị ban đầu tối ưu, UTBMBT sẽ tái phát và cần được điều trị. Điều trị UTBMBT tái phát còn gặp nhiều khó khăn. Nghiên cứu này nhằm đánh giá một số đặc điểm lâm sàng, cận lâm sàng UTBMBT tái phát kháng platinum và kết quả điều trị phác đồ paclitaxel nhóm bệnh nhân này. Phương pháp nghiên cứu: Chúng tôi đưa vào nghiên cứu 65 bệnh nhân được điều trị phác đồ paclitaxel cho ung thư biểu mô buồng trứng tái phát khángplatinum, thỏa mãn các tiêu chuẩn lựa chọn và tiêu chuẩn loại trừ. Với phương pháp nghiên cứu mô tả cắt ngang. Kết quả: Các vị trí tái phát thường gặp nhất là hạch (54,3%), phúc mạc (50%), gan (23,9%). Tăng CA125 ở thời điểm tái phát (77,8%) tỷ lệ đáp ứng chung là 22,5%. Tỷ lệ kiểm soát bệnh (bao gồm đáp ứng hoàn toàn, đáp ứng một phần và bệnh giữ nguyên) đạt 62,5%. Trung vị thời gian sống thêm không tiến triển 26,1 tuần (CI 95%: 20,9 - 28,4). Độc tính trên hệ tạo huyết là giảm bạch cầu đa nhân trung tính độ 1,2. Độc tính trên gan 9,3% chủ yếu tăng men gan độ 1,2. Không có độc tính trên thận. Các tác dụng không mong muốn khác như rụng tóc độ 2: 2,7%, viêm miệng gặp ở 2,1% bệnh nhân, thần kinh cảm giác 15%, chỉ gặp ở độ 1. Có mối liên quan giữa đáp ứng điều trị và nồng độ CA 125. Kết luận: Phác đồ paclitaxel sử dụng điều trị UTBMBT tái phát kháng platinum là phác đồ phù hợp về tính hiệu quả và an toàn cho các bệnh nhân UTBMBT đã trải qua phác đồ hóa trị trước đó. ABSTRACT OUTCOMES OFRECURRENT EPITHELIAL OVARIAN CANCER PATIENTS TREATED WITH PACLITAXEL REGIMEN AT K HOSPITAL Introduction: Epithelial ovarian cancer is a malignant abnormality of the epithelial cell of the ovary. The disease has a poor prognosis. Despite optimal initial therapy, the majority of patients will relapse and require further treatment. Treatment of recurrent ovarian cancer is still challenging. This study aims to describe clinical and subclinical characteristics of patients with platinum - resistant relapsed ovarian carcinoma and evaluate the treatment results of the paclitaxel regimen on these patients. Methods: We enrolled 65 patients with platinum - resistant recurrent epithelial ovarian cancer treated with paclitaxel regimen, met the inclusion and exclusion criteria. Results: The most common recurrent sites were lymph nodes (54.3%), peritoneum (50%), and liver (23.9%). CA125 increased at the time of recurrence (77.8%), the overall response rate was 22.5%. Disease control rates (including complete response, partial response, and stable disease) were achieved at 62.5%. Median progression - free survival was 26.1 weeks (95% CI: 20.9 - 28.4). Hematopoietic system toxicities include neutropenia of grade 1, 2. Hepatotoxicity occupied 9.3%, mainly liver enzymes elevation of grade 1, 2. No renal toxicity was observed. Other undesirable effects include hair loss of grade 2 (2.7%), stomatitis(2.1%), sensory nerve 15% but only grade 1. There was a relationship between treatment response and CA 125 levels. Conclusion: The paclitaxel regimen used to treat platinum - resistant recurrent epithelial ovarian cancer is the appropriate regimen in terms of efficacy and safety. After several lines of chemotherapy regimens. Keywords: Recurrent epithelial ovarian cancer, platinum - resistant, paclitaxel.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15516-e15516
Author(s):  
Amit Rauthan ◽  
Poonam Patil ◽  
S. P. Somashekhar ◽  
Shabber Zaveri

e15516 Background: The standard of care for patients with recurrent platinum resistant ovarian cancer is treatment with non cross-resistant drugs. Carboplatin retreatment is usually not an option in the platinum resistant population. Weekly paclitaxel has been tried in recurrent patients. But paclitaxel can cause hypersensitivity reactions due to its Cremophor based solvent. nab-paclitaxel being a nano-particle albumin bound paclitaxel is devoid of this toxictity. Also, it is thought that nab-paclitaxel may have a higher intratumoral uptake leading to enhanced anti-tumor action. We looked at a regimen using weekly carboplatin with weekly nab-paclitaxel in platinum resistantrelapsed carcinoma ovary who had failed multiple lines of treatment. Methods: We treated 10 patients with recurrent platinum resistant ovarian cancer with measurable disease with nab-paclitaxel 100mg/m2 on days 1,8,15 with carboplatin at AUC 1.5 on days 1,8,15 intravenously, repeated every 28 days for 4 cycles. All patients had received 3 or more lines of chemotherapy for recurrent disease. We looked for response rate, progression free survival and toxicities. Results: Three patients had complete response, 5 patients had partial response and 2 patients had disease progression. Median PFS was 6 months. There were no instances of paclitaxel induced hypersensitivity reactions. Two patients developed grade 3 neutropenia. One patient developed grade 3 thrombocytopenia. Three patients required blood transfusions. One patient developed grade 3 neuropathy. Conclusions: Weekly combination of nab-paclitaxel with weekly carboplatin is a safe and potentially active treatment in recurrent platinum resistant ovarian cancers who had failed multiple lines of treatment. Considering the efficacy and favorable toxicity profile, this weekly combination needs to be tested in a larger number of patients.


2021 ◽  
pp. ijgc-2020-002239
Author(s):  
Oren Smaletz ◽  
Gustavo Ismael ◽  
Maria Del Pilar Estevez-Diz ◽  
Ivana L O Nascimento ◽  
Ana Luiza Gomes de Morais ◽  
...  

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.


1999 ◽  
Vol 17 (2) ◽  
pp. 501-501 ◽  
Author(s):  
John A. Bridgewater ◽  
Ann E. Nelstrop ◽  
Gordon J.S. Rustin ◽  
Martin E. Gore ◽  
William P. McGuire ◽  
...  

PURPOSE: To assess CA-125 as a measure of response in patients treated with paclitaxel. PATIENTS AND METHODS: One hundred forty-four patients treated with paclitaxel derived from four different trials and 625 patients treated with platinum from two trials were analyzed using precisely defined 50% and 75% reductions in CA-125. The standard and CA-125 response rates to paclitaxel and platinum were compared. In addition, we analyzed individual patient groups in which there was a difference in response according to the two response criteria. RESULTS: Patients with stable disease as determined by standard criteria who were treated with platinum and responded according to CA-125 criteria have an improved median progression-free survival compared with patients with stable disease who did not respond according to CA-125 criteria (10.6 v 4.8 months; P < .001). Standard and CA-125 response rates for patients treated with platinum (58.93% v 61.31%, respectively) and paclitaxel (30.65% v 31.67%, respectively) were very similar, as were rates of false-positive prediction of response by CA-125 (platinum 2.2% and paclitaxel 2.9%). Responders to paclitaxel had a significantly improved progression-free survival compared with nonresponders by both standard criteria (median progression-free survival, 6.8 v 2.5 months; P < .001) and CA-125 criteria (median progression-free survival, 6.8 v 3.4 months; P < .001). CONCLUSION: For assessing activity of therapy for ovarian cancer, these data show that precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria. We propose that they may be used as a measure of response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer. Sensitivity is maintained whether patients are treated with platinum or paclitaxel.


2016 ◽  
Vol 12 (7) ◽  
pp. e775-e783 ◽  
Author(s):  
Nicole P. Chappell ◽  
Caela R. Miller ◽  
Aaron D. Fielden ◽  
Jason C. Barnett

Purpose: Although the Food and Drug Administration has approved incorporation of bevacizumab (BEV) into the treatment of platinum-resistant ovarian cancer (PROC), cost-value measures are an essential consideration, as evidenced by the recent ASCO Value Framework initiative. We assessed the cost-effectiveness and reviewed the net health benefit (NHB) of this expensive treatment. Methods: A cost-effectiveness decision model was constructed using results from a phase III trial comparing BEV plus cytotoxic chemotherapy with chemotherapy alone in patients with PROC. The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA) trial demonstrated improvement in progression-free survival and quality of life in patients receiving BEV. Costs, paracentesis rates, and adverse events were incorporated, including subgroup analysis of different partner chemotherapy agents. Results: Inclusion of BEV in the treatment of platinum-resistant recurrent ovarian cancer meets the common willingness-to-pay incremental cost-effectiveness ratio (ICER) threshold of $100,000 per progression-free life-year saved (LYS) for 15-mg/kg dosing and approaches this threshold for 10-mg/kg dosing, with an ICER of $160,000. In sensitivity analysis, reducing the cost of BEV by 13% (from $9,338 to $8,100 per cycle) allows 10-mg/kg dosing to reach a $100,000 ICER. Exploratory analysis of different BEV chemotherapy partners showed an ICER of $76,000 per progression-free LYS (6.5-month progression-free survival improvement) and $54,000 per LYS (9.1-month overall survival improvement) for the addition of BEV to paclitaxel once per week. Using the ASCO framework for value assessment, the NHB score for BEV plus paclitaxel once per week is 48. Conclusion: Using a willingness-to-pay threshold of $100,000 ICER, the addition of BEV to chemotherapy either demonstrates or approaches cost-effectiveness and NHB when added to the treatment of patients with PROC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5039-5039
Author(s):  
Emma L. Barber ◽  
Nikki Lynn Neubauer ◽  
Emese Zsiros ◽  
Julian C. Schink

5039 Background: This study was undertaken to determine the progression free survival and overall survival in heavily pre-treated patients with recurrent ovarian carcinoma treated with bevacizumab and metronomic oral cyclophosphamide. Methods: An IRB-approved retrospective review was performed for all patients with recurrent ovarian, fallopian tube or primary peritoneal carcinomas treated with intravenous bevacizumab 10mg/kg every 14 days and oral cyclophosphamide 50mg daily between January 2006 and December 2010. Response to treatment was determined by change in disease status according to RECIST criteria and/or CA-125 levels. Results: Sixty-six eligible patients were identified with a median age of 58 years. Fifty-five patients (83%) originally had optimal cytoreduction and all were platinum resistant. Median time from diagnosis to beginning bevacizumab and cyclophosphamide was 36 months. Median number of prior chemotherapy treatments was 7.5 (range 3-16). Eight patients (12.1%) had side effects which required discontinuing bevacizumab and cyclophosphamide, most common were hypertension, proteinuria, and fatigue. There was one bowel perforation (1.5%). A complete response was noted in 7 patients (10.6%), partial response was seen in 21 patients (31.8%) with an overall response rate of 42.4%. Fifteen patients (22.7%) had stable disease and 23 (34.8%) had disease progression. Median progression free survival (PFS) for responders was 5 months (range 2-14) and 11 months (range 4-14) for those with a complete response. Median overall survival (OS) from start of bevacizumab and cyclophosphamide for responders was 20 months (range 2-56) and 9 months (range 1-51) for nonresponders. Conclusions: Bevacizumab and cyclophosphamide is an effective, well-tolerated chemotherapy regimen in heavily pre-treated patients with recurrent ovarian carcinoma which significantly improves PFS and OS in responders. Response rates were significantly better than the rates we have reported in this same group of patients receiving topotecan (22%) or liposomal doxorubicin (25%) and were superior to reported rates for single agent bevacizumab (18%) in patients with only 2-3 prior regimens.


2008 ◽  
Vol 18 (3) ◽  
pp. 428-431 ◽  
Author(s):  
T. Le ◽  
L. Hopkins ◽  
K. A. Baines ◽  
L. Rambout ◽  
M. Fung-Kee-Fung

Topotecan administered on a weekly basis has been reported to possess antineoplastic activities with lower toxicities than the standard 5-day regimen every 3 weeks. We studied the activity of weekly topotecan regimen in recurrent platinum-resistant epithelial ovarian cancer patients. Ovarian cancer patients with documented platinum-resistant recurrences were treated with weekly intravenous topotecan (4 mg/m2) on days 1, 8, and 15 on a 28-day cycle. Prospective data collection included patients' demographics together with disease- and treatment-related toxicities. Responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and CA125 criteria. Progression-free survival and overall survival time from commencement of weekly treatment were estimated using the Kaplan–Meier method. All P values less than 0.05 were considered to be statistically significant. Twenty-two patients were treated. Weekly topotecan was used most commonly as third-line chemotherapy (range 1–5). A total of 244 weekly treatments were administered, with a median of 12 weekly treatments per patient. Two patients (9%) reported grade 3/4 gastrointestinal and two had grade 3/4 hematologic toxicities respectively. No dose reduction or treatment delay was required. Partial response was observed in two patients (9.1%) and another seven patients (31.8%) showed stable disease. No significant association was observed between best clinical response and patients' initial platinum sensitivity status. The estimated median progression-free survival was 20.9 weeks (95% CI 11.2–30.5) from the start of the weekly regimen. Weekly topotecan is well tolerated in patients with recurrent platinum-resistant ovarian cancer with modest activity.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5558-5558 ◽  
Author(s):  
Radoslav Chekerov ◽  
Peter Klare ◽  
Petra Krabisch ◽  
Jochem Potenberg ◽  
Georg Heinrich ◽  
...  

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.


1999 ◽  
Vol 17 (7) ◽  
pp. 2069-2069 ◽  
Author(s):  
P. A. Vasey ◽  
J. Paul ◽  
A. Birt ◽  
E. J. Junor ◽  
N. S. Reed ◽  
...  

PURPOSE: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m2 and docetaxel 75 mg/m2); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m2 and docetaxel 85 mg/m2). RESULTS: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION: Cisplatin and docetaxel can be administered at doses of 75 mg/m2 and 75 mg/m2, respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m2 adds unacceptable hematologic toxicity and potential risks to the patient.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15040-15040
Author(s):  
F. Abushahin ◽  
E. C. Grendys ◽  
J. R. Lurain ◽  
D. K. Singh ◽  
A. W. Rademaker ◽  
...  

15040 Background: Topotecan is currently used to treat recurrent ovarian cancer after failure of platinum-based therapy. The FDA-recommended regimen (1.5 mg/m2 for 5 consecutive days of a 21-day cycle) is associated with a high incidence of grade 3/4 myelosuppression. Alternate dosing and scheduling may increase patient convenience and reduce toxicity. The objective of this study is to evaluate toxicity, response and progression free survival of weekly topotecan therapy in women with primary and secondary platinum resistant ovarian cancer after failure of 1 or more regimens. Methods: A retrospective analysis of 59 patients that received weekly topotecan with a median dose of 3.75 on days 1, 8, and 15 of a 28-day cycle treated between November 2002 and May 2005. All patients had recurrent epithelial ovarian cancer with primary or secondary resistance to platinum. Disease response was evaluated by CA-125 levels, physical exam, and when appropriate by imaging studies. Toxicity was evaluated using the NCI Common Toxicity Criteria. Results: Response to therapy was noted in (22%) 13 of 59 patients (complete 6.75%, partial 15.25%). Stable disease was noted in 19 patients (32.2%) and progression in 25 patients (42.4%). Two patients (3.4%) had significant side effects that warranted the discontinuation of therapy. There was no significant difference in response to therapy between patients with primary and secondary platinum resistance. A total of 204 cycles were given with a median of 3 (1–12) cycles per patient. Grade 3 and 4 myelosuppression were rare with 1 cycle (0.5%) with grade 3 leukopenia, 15 cycles (6.4%) with grade 3 or 4 neutropenia, 1 cycle (0.5%) with grade 3 anemia, and 1 cycle (0.5%) with grade 3 thrombocytopenia. No patients were admitted with neutropenic fever. The Median Progression-free-survival for responders was 195 days (56–471). Conclusions: Weekly topotecan is a well tolerated and effective regimen for platinum resistant ovarian cancer with considerable less hematological toxicity when compared with historical data for the 5-day regimen. [Table: see text]


2013 ◽  
Vol 23 (5) ◽  
pp. 815-822 ◽  
Author(s):  
Xiaoxiang Chen ◽  
Jing Zhang ◽  
Wenjun Cheng ◽  
Doo Young Chang ◽  
Jianfei Huang ◽  
...  

ObjectiveMost patients with epithelial ovarian cancer achieve a complete clinical remission (CCR) with normal CA-125 but will still relapse and die from their disease. The present study was designed to determine whether CA-125 levels before, during, and after primary treatment provide prognostic information for both type I and type II ovarian cancer.MethodsIn this retrospective study, we identified 410 patients with epithelial ovarian cancer who had achieved a CCR between 1984 and 2011. A Cox proportional hazards model and log-rank test were used to assess associations between the nadir CA-125, histotype, and prognosis.ResultsThe baseline serum CA-125 concentration was higher in patients with type II ovarian cancer than in those with type I ovarian cancer (P < 0.001). The nadir CA-125 was an independent predictor of progression-free survival (PFS; P < 0.001) and overall survival (OS; P = 0.035) duration. The PFS and OS durations were 21.7 and 79.4 months in patients with CA-125 of 10 U/mL or less and 13.6 and 64.6 months in those with CA-125 of 11 to 35 U/mL, respectively (P = 0.01 and P = 0.002, respectively). Histotype was an independent predictor of PFS (P = 0.041): the PFS and OS durations of the patients with type I ovarian cancer were longer than those of the patients with type II ovarian cancer (P < 0.001 and P < 0.001, respectively).ConclusionsThe nadir CA-125 and histotype are predictive of PFS and OS durations in patients with ovarian cancers who experienced a CCR. Progression-free survival and OS durations were shorter in the patients with CA-125 levels of 11 to 35 U/mL and type II disease than in those with CA-125 levels of 10 U/mL or less and type I ovarian cancer.


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