scholarly journals Pazopanib and Oral Cyclophosphamide in Women With Platinum-Resistant or -Refractory Epithelial Ovarian Cancer

2020 ◽  
pp. 542-547 ◽  
Author(s):  
Seema Gulia ◽  
Jaya Ghosh ◽  
Jyoti Bajpai ◽  
Sushmita Rath ◽  
Amita Maheshwari ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Disease Progression ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Oral Cyclophosphamide ◽  
Platinum Resistant ◽  
Hand Foot Syndrome ◽  
Platinum Refractory ◽  
Grade 3

PURPOSE Women with recurrent, multiply-treated epithelial ovarian cancer (EOC) have unfavorable prognosis with limited treatment options after failure of platinum-based regimens. We report here a retrospective analysis of women with recurrent, platinum-resistant EOC treated with an oral regimen of pazopanib and cyclophosphamide. PATIENTS AND METHODS Women with recurrent platinum-resistant or -refractory EOC were treated with pazopanib (600 mg orally daily in 2 divided doses, 400 and 200 mg) and cyclophosphamide (50 mg orally daily for 21 days every 28 days) until disease progression or unacceptable toxicity. RESULTS Twenty patients (17 with platinum-resistant and 3 with platinum-refractory disease) were treated between April 2014 and April 2018. Patients had a median age of 52 years (range, 40-60 years) and median of 4 previous lines of chemotherapy (range, 2-8 previous lines), including 3 patients with progressive disease on bevacizumab. Patients received a median of 6 cycles (range, 2-48 cycles) of pazopanib and cyclophosphamide, with best responses of partial response in 9 patients (45%, including 1 of 3 patients treated previously with bevacizumab), stable disease in 6 patients (30%), and disease progression in 5 patients (25%). The median progression-free survival time was 5.5 months, and median overall survival was 9.5 months. Common adverse events (grade 3 or 4) were fatigue (25%), diarrhea (15%), hand-foot syndrome (10%), mucositis (10%), transaminitis (5%), and hypertension (5%). Dose reduction as a result of toxicity was required in 14 patients (70%), and no patient stopped treatment as a result of toxicity. CONCLUSION Pazopanib plus oral cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory EOC.

Prospective evaluation of weekly topotecan in recurrent platinum-resistant epithelial ovarian cancer

2008 ◽  
Vol 18 (3) ◽  
pp. 428-431 ◽  
Author(s):  
T. Le ◽  
L. Hopkins ◽  
K. A. Baines ◽  
L. Rambout ◽  
M. Fung-Kee-Fung
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Free Survival ◽  
Platinum Resistant ◽  
Kaplan Meier ◽  
Third Line ◽  
Grade 3

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.

Phase II Trial of Irinotecan in Patients With Metastatic Epithelial Ovarian Cancer or Peritoneal Cancer

2003 ◽  
Vol 21 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Diane C. Bodurka ◽  
Charles Levenback ◽  
Judith K. Wolf ◽  
Jacalyn Gano ◽  
J. Taylor Wharton ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Median Survival ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant ◽  
Platinum Refractory

Purpose: To evaluate the efficacy and toxicity of irinotecan in patients with metastatic platinum-resistant or platinum-refractory epithelial ovarian cancer or primary peritoneal cancer.Patients and Methods: Thirty-one patients with measurable disease were enrolled in our study at The University of Texas M.D. Anderson Cancer Center. Twenty-five of these patients were treated with irinotecan at a dose of 300 mg/m2intravenously for 90 minutes every 3 weeks; the remaining six patients were treated with 250 mg/m2because their age was greater than 65 years. Median age was 57 years (range, 38 to 74 years). The majority (84%) had a Zubrod performance status of 0. All patients were evaluated for irinotecan toxicity, and 29 (94%) were evaluable for response.Results: The overall response rate was 17.2%. One patient (3%) had a complete response, four (14%) had partial responses, 14 (48%) had stable disease, and 10 had (35%) disease progression. Median progression-free survival was 2.8 months (range, 1.1 to 16 months), median duration of response was 1.4 months (range, 0.7 to 10.1 months); median survival from primary diagnosis was 24.3 months (range, 6.5 to 85.7 months); and median survival from initiation of irinotecan was 10.1 months (range, 2.3 to 34 months). Major toxicities included fatigue (16 patients), neutropenia (11 patients), diarrhea (nine patients), nausea (10 patients), and anorexia (seven patients). Eleven patients required dose reductions because of these toxicities. No treatment-related deaths occurred.Conclusion: Irinotecan has moderate efficacy and substantial toxicity in patients with metastatic platinum-resistant or platinum-refractory epithelial ovarian or primary peritoneal cancer.

Apatinib in treating patients with platinum-resistant or platinum-refractory recurrent or metastatic nasopharyngeal carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17502-e17502
Author(s):  
Xiaozhong Chen ◽  
Changjuan Tao
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Artery Dissection ◽  
Intention To Treat ◽  
Platinum Resistant ◽  
Metastatic Nasopharyngeal Carcinoma ◽  
Hand Foot Syndrome ◽  
Platinum Refractory ◽  
Grade 3

e17502 Background: To evaluate the efficacy and safety of apatinib in treating patients with platinum-resistant or platinum-refractory recurrent or metastatic nasopharyngeal carcinoma. Methods: In this phase 2, single-arm, prospective study, we recruited patients aged 18–65 years with platinum-resistant or platinum-refractory recurrent /metastatic nasopharyngeal carcinoma. Patients were treated with apatinib at an initial dose of 500 mg once daily and continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was clinical benefit rate (CBR) and toxicity. Secondary endpoints included progression-free survival (PFS) at 3 months and overall survival (OS). We used Simon’s two-stage design, and analysed efficacy and toxicity in the intention-to-treat and per-protocol populations. This study is registered with ClinicalTrials.gov, number NCT03213587. Results: Between Aug 5,2017 and Oct 13,2018, we enrolled 16 patients. Until the final follow-up (Jan 14, 2019), the CBR (complete response + partial response+ stable disease) was 69.2% (9/13) in the per-protocol population. Median PFS and 3-month PFS rate were 3.70 (95% CI, 0-8.771) months and 67.1%, respectively. Median OS and 1-year OS rate were 12.9 (95% CI 5.56-20.23) months and 47.9%, respectively. The most common grade 3-4 adverse events were neutropenia (1[6.25%]), hand-foot syndrome (2[12.5%]), albuminuria (2[12.5%]), hypertension (1[6.25%]), hyponatremia (1[6.25%]), artery dissection (1[6.25%]) and nasopharyngeal hemorrhage (2[12.5%]) in the intention-to-treat population. Serious adverse event was reported in one patient who died of nasopharyngeal hemorrhage. Conclusions: Apatinib achieved excellent disease control in platinum-resistant or platinum-refractory recurrent or metastatic nasopharyngeal carcinoma. More attention needs to be paid to toxicity management. Clinical trial information: NCT03213587.

scholarly journals To assess the role of addition of bevacizumab therapy to carboplatin and paclitaxel as frontline treatment of epithelial ovarian cancer

2016 ◽  
Author(s):  
Richa Vatsa ◽  
Sunesh Kumar ◽  
Lalit Kumar
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Disease Progression ◽  
Safety Profile ◽  
Haematological Toxicity ◽  
Progression Free Survival ◽  
New Drugs ◽  
Secondary Outcome ◽  
Vegf Receptor ◽  
Persistent Proteinuria

Introduction: Efforts are going on for development of new drugs for epithelial ovarian cancer (EOC). We assessed safety profile of bevacizumab, a VEGF receptor blocking antibody in treatment of EOC. Methods: We assigned women with EOC to carboplatin (area under curve, 5 or 6) and paclitaxel (175 mg/square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (15 mg/kilogram body weight), given concurrently every 3 weeks for 5 or 6 cycles and continued for 30 additional cycles. Primary outcome measures was safety profile of bevacizumab and secondary outcome was to see progression free survival (PFS). Results: Out of 30 patients, 10 were in Bevacizuma arm (Arm A) and 20 in conventional chemotherapy arm (Arm B). Haematological toxicity, GI perforation and proteinuria was similar in both. Other toxicities e.g. bleeding complication (p = 0.002) and hypertension (p = 0.04) was more in Arm A. PFS was similar in both arms; 24 months in Arm A and 22 months in Arm B (p = 0.565). 4 (40%) patients in arm A discontinued treatment, two (20%) because of disease progression after PFS of 9 and 6 months, two because of development of toxicity considered to be due to bevacizumab; of which one developed jejenal perforation and disease progression after PFS of 6 months and 1 because of development of persistent proteinuria of grade 3 after 18 months. Conclusion: Bevacizumab therapy does not improve PFS in EOC but increases toxicity spectrum of chemotherapy.

scholarly journals Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer, therapeutic treatment options for platinum-resistant ovarian cancer

2021 ◽  
Author(s):  
Natasha Rinne ◽  
Elizabeth L. Christie ◽  
Anastasia Ardasheva ◽  
Chun Hei Kwok ◽  
Nikita Demchenko ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Treatment Options ◽  
Mtor Pathway ◽  
Therapeutic Treatment ◽  
Platinum Resistant

scholarly journals Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 24 ◽  
Author(s):  
Chin-Jui Wu ◽  
Vignesh Sundararajan ◽  
Bor-Ching Sheu ◽  
Ruby Yun-Ju Huang ◽  
Lin-Hung Wei
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Microenvironmental Factors ◽  
Therapeutic Opportunity ◽  
Molecular Therapeutic

Epithelial ovarian cancer (EOC) is the most lethal of all gynecologic malignancies. Despite advances in surgical and chemotherapeutic options, most patients with advanced EOC have a relapse within three years of diagnosis. Unfortunately, recurrent disease is generally not curable. Recent advances in maintenance therapy with anti-angiogenic agents or Poly ADP-ribose polymerase (PARP) inhibitors provided a substantial benefit concerning progression-free survival among certain women with advanced EOC. However, effective treatment options remain limited in most recurrent cases. Therefore, validated novel molecular therapeutic targets remain urgently needed in the management of EOC. Signal transducer and activator of transcription-3 (STAT3) and STAT5 are aberrantly activated through tyrosine phosphorylation in a wide variety of cancer types, including EOC. Extrinsic tumor microenvironmental factors in EOC, such as inflammatory cytokines, growth factors, hormones, and oxidative stress, can activate STAT3 and STAT5 through different mechanisms. Persistently activated STAT3 and, to some extent, STAT5 increase EOC tumor cell proliferation, survival, self-renewal, angiogenesis, metastasis, and chemoresistance while suppressing anti-tumor immunity. By doing so, the STAT3 and STAT5 activation in EOC controls properties of both tumor cells and their microenvironment, driving multiple distinct functions during EOC progression. Clinically, increasing evidence indicates that the activation of the STAT3/STAT5 pathway has significant correlation with reduced survival of recurrent EOC, suggesting the importance of STAT3/STAT5 as potential therapeutic targets for cancer therapy. This review summarizes the distinct role of STAT3 and STAT5 activities in the progression of EOC and discusses the emerging therapies specifically targeting STAT3 and STAT5 signaling in this disease setting.

scholarly journals Bevacizumab in the Management of Epithelial Ovarian Cancer

2013 ◽  
Vol 09 (02) ◽  
pp. 129
Author(s):  
Maurie Markman ◽  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Single Agent ◽  
Strong Support ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Phase Iii ◽  
Platinum Sensitive ◽  
Platinum Resistant

Preclinical investigations have provided strong support for the hypothesis that angiogenesis is a potent driver of epithelial ovarian cancer progression. Phase II data have revealed the activity of single-agent bevacizumab in previously treated and clinically defined platinum-resistant ovarian cancer. Several reported phase III randomized trials, involving primary and both ‘platinum-sensitive’ recurrent and platinum-resistant disease, have demonstrated the addition of bevacizumab to a cytotoxic chemotherapy regimen improves progression-free survival compared with chemotherapy alone. While there continues to be considerable debate regarding the optimal dose, timing, and duration of bevacizumab administration in ovarian cancer, the existing data provide strong support for an important role for this agent in the overall management paradigm for this malignancy.

A phase II trial of combination irinotecan and oral etoposide chemotherapy in recurrent ovarian cancer: A Tohoku Gynecologic Cancer Unit (TGCU) study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5558-5558
Author(s):  
S. Kumagai ◽  
T. Shoji ◽  
Y. Yokoyama ◽  
T. Takano ◽  
H. Mizunuma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Treatment Options ◽  
Gynecologic Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Oral Etoposide ◽  
Eligibility Criteria ◽  
Platinum Resistant

5558 Background: Various problems still exist in the management of recurrent ovarian cancer and there are limited treatment options especially for the platinum resistant patients (pts). We conducted a phase II study to evaluate the efficacy and safety of the combination irinotecan/oral etoposide chemotherapy. Methods: Eligibility criteria included recurrent ovarian cancer with measurable disease or positive CA125, preserved organ function, and aged 20–75. Treatment was conducted with irinotecan (60 mg/m2 iv, day 1, 15) and oral etoposide (50 mg/body day 1–21), q 28 days until disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) and secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: 38pts were enrolled on this study from May 2003 to April 2007, and all pts were eligible. Median age was 57 yrs (range 37–74). PS 0 in 24 pts, 1 in 10 pts, and 2 in 4 pts. Median number of previous regimen was 2 (range 1–4). Median treatment cycles were 6 (range 2–27). RR (CR+PR) was 18/38 (47.4%), and CR+PR+SD rate was 31/38 (81.6%). Grade 3/4 adverse effect included leukopenia (50.0%), neutropenia (52.6%), anemia (18.4%) and thrombocytopenia (2.6%), nausea/vomiting (7.9%) and diarrhea (2.6%). Treatment-related death was not observed. Median PFS was 7 months (range 1–33) and OS was 19 months (range 4–60). Among 20 pts with platinum resistant cases, RR was 6/20 (30.0%), CR+PR+SD rate was 14/20 (70.0%), median PFS was 6 months (range 1–33), and OS was 24 months (range 5–60). Conclusions: Combination irinotecan/oral etoposide chemotherapy can achieve a superior management for the recurrent ovarian cancer without declining QOL, and also has the possibility to be one of the most effective regimens as second-line chemotherapy. No significant financial relationships to disclose.

Randomized phase II CLIO study on olaparib monotherapy versus chemotherapy in platinum-resistant ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5507-5507 ◽  
Author(s):  
Adriaan Vanderstichele ◽  
Els Van Nieuwenhuysen ◽  
Sileny Han ◽  
Nicole Concin ◽  
Toon Van Gorp ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Clinical Endpoints ◽  
Platinum Resistant ◽  
Randomized Phase Ii ◽  
Duration Of Response ◽  
Grade 3

5507 Background: The CLIO trial (NCT02822157) evaluated olaparib single-agent therapy versus standard of care chemotherapy in platinum-resistant (recurrence within 6 months after last platin) ovarian cancer (PROC). Methods: Eligible patients with measurable disease and ≥1 prior line of chemotherapy were randomized 2:1 to Olaparib (OLA) monotherapy (300 mg tablets, BID) or physician’s choice chemotherapy (CT; PLD 40 mg/m2 q 4 wks; Topotecan 1.25 mg/m2 day 1—5 q 3 wks; Paclitaxel 80 mg/m2 day 1, 8,15 q 3 wks; Gemcitabine 1000 mg/m2 day 1, 8 and 15 q 4 wks). Primary endpoint was objective overall response (ORR) per RECIST v1.1. Germline BRCA status was available for all patients. Disease control rate (DCR) was defined as response for at least 12 wks. Results: 100 patients with PROC were randomized 2:1 to OLA (N = 67) or CT (N = 33). Median prior lines of treatment was 3 (range: 1—8). ORR (unconfirmed) was 18% (12/67) for OLA and 6% (2/33) for CT. ORR for OLA was 38% (5/13) in gBRCAm and 13% (7/54) in gBRCAwt patients. Of note, 2 patients with gBRIP1 mutation had no response under OLA. DCR was 35.8% (24/67) for OLA and 42% (14/33) for CT. DCR under OLA in gBRCAm was 62% (8/13) compared to 30% (16/54) in gBRCAwt disease. The median duration of response (DOR) and the median progression-free survival (PFS) was similar: 5.4 months vs 4.5 months (DOR) and 2.9 vs 3.4 months (PFS) for OLA and CT, respectively. Grade ≥3 treatment-related AEs occurred in 60% vs 52% for OLA and CT, respectively. Somatic HRR mutation analysis is ongoing and will be presented. Conclusions: Olaparib monotherapy showed a favorable response rate in PROC compared with chemotherapy also in gBRCAwt patients. Analysis of clinical endpoints in relation to HRR is ongoing and will be presented. Clinical trial information: NCT02822157.

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