scholarly journals Pharmacokinetics and clinical response to single agent rucaparib in a dialysis dependent patient with BRCA associated breast and recurrent ovarian cancer

2018 ◽  
Vol 26 ◽  
pp. 91-93 ◽  
Author(s):  
Justin A. Harold ◽  
Stephanie C. Free ◽  
William H. Bradley
Keyword(s):  
Ovarian Cancer ◽  
Clinical Response ◽  
Single Agent ◽  
Recurrent Ovarian Cancer ◽  
Dependent Patient

scholarly journals Matrix Drug Screen Identifies Synergistic Drug Combinations to Augment SMAC Mimetic Activity in Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3784
Author(s):  
Anne M. Noonan ◽  
Amanda Cousins ◽  
David Anderson ◽  
Kristen P. Zeligs ◽  
Kristen Bunch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
Single Agent ◽  
Recurrent Ovarian Cancer ◽  
Drug Combinations ◽  
Smac Mimetic ◽  
Synergistic Drug Combinations

Inhibitor of apoptosis (IAP) proteins are frequently upregulated in ovarian cancer, resulting in the evasion of apoptosis and enhanced cellular survival. Birinapant, a synthetic second mitochondrial activator of caspases (SMAC) mimetic, suppresses the functions of IAP proteins in order to enhance apoptotic pathways and facilitate tumor death. Despite on-target activity, however, pre-clinical trials of single-agent birinapant have exhibited minimal activity in the recurrent ovarian cancer setting. To augment the therapeutic potential of birinapant, we utilized a high-throughput screening matrix to identify synergistic drug combinations. Of those combinations identified, birinapant plus docetaxel was selected for further evaluation, given its remarkable synergy both in vitro and in vivo. We showed that this synergy results from multiple convergent pathways to include increased caspase activation, docetaxel-mediated TNF-α upregulation, alternative NF-kB signaling, and birinapant-induced microtubule stabilization. These findings provide a rationale for the integration of birinapant and docetaxel in a phase 2 clinical trial for recurrent ovarian cancer where treatment options are often limited and minimally effective.

A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer

2008 ◽  
Vol 18 (3) ◽  
pp. 400-406 ◽  
Author(s):  
J. D. Wright ◽  
A. A. Secord ◽  
T. M. Numnum ◽  
R. P. Rocconi ◽  
M. A. Powell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Response ◽  
Response Rate ◽  
Single Agent ◽  
Chylous Ascites ◽  
Recurrent Ovarian Cancer ◽  
Cytotoxic Agent ◽  
Combination Group ◽  
Factors Associated ◽  
Grade 3

While bevacizumab has shown activity in recurrent ovarian cancer, a higher than expected incidence of bowel perforations has been reported in recent trials. We sought to determine factors associated with toxicity and tumor response in patients with relapsed ovarian cancer treated with bevacizumab. A retrospective review of patients with recurrent ovarian cancer treated with bevacizumab was undertaken. Response was determined radiographically and through CA125 measurements. Statistical analysis to determine factors associated with toxicity and response was performed. Sixty-two eligible patients were identified. The cohort had received a median of 5 prior chemotherapy regimens. Single-agent bevacizumab was administered to 12 (19%), while 50 (81%) received the drug in combination with a cytotoxic agent. Grade 3–5 toxicities occurred in 15 (24%) patients, including grade 3–4 hypertension in 4 (7%), gastrointestinal perforations in 7%, and chylous ascites in 5%. Development of chylous ascites and gastrointestinal perforations appeared to correlate with tumor response. The overall response rate was 36% (4 complete response, 17 partial response), with stable disease in 40%. A higher objective response rate was seen in the bevacizumab combination group compared to single-agent treatment (43% vs 10%) (P = 0.07). However, 29 grade 3–5 toxic episodes were seen in the combination group vs only 1 in the single-agent bevacizumab cohort (P = 0.071). We conclude that bevacizumab demonstrates promising activity in recurrent ovarian cancer. The addition of a cytotoxic agent to bevacizumab improved response rates at the cost of increased toxicity. Gastrointestinal perforations occurred in 7%. The perforations occurred in heavily pretreated patients who were responding to therapy

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

2007 ◽  
Vol 17 (2) ◽  
pp. 359-366 ◽  
Author(s):  
P. Harnett ◽  
M. Buck ◽  
P. Beale ◽  
A. Goldrick ◽  
S. Allan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Recurrent Ovarian Cancer ◽  
Ca 125 ◽  
Platinum Sensitive ◽  
Best Response ◽  
Platinum Based Chemotherapy ◽  
Group A ◽  
Intent To Treat ◽  
Group B

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

Phase I and pharmacokinetic study of the novel VEGF-directed fusion protein, aflibercept, in combination with docetaxel in women with recurrent ovarian, fallopian tube, and primary peritoneal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5549-5549
Author(s):  
R. L. Coleman ◽  
A. Kamat ◽  
R. Iyer ◽  
V. Kundra ◽  
M. Garcia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fusion Protein ◽  
Phase I ◽  
Cancer Patients ◽  
Fdg Pet ◽  
Single Agent ◽  
Recurrent Ovarian Cancer ◽  
Circulating Endothelial Cells ◽  
Efficacy Evaluation ◽  
Dce Mri

5549 Background: VEGF blockade has proved to be a promising therapeutic strategy in solid tumors, including ovarian. Aflibercept, a novel fusion protein consisting of the extracellular domains of VEGFR1/2 binds VEGF A, B and PlGF. Aflibercept has been studied as a single agent in heavily pretreated ovarian cancer patients. We hypothesized that the combination of aflibercept and docetaxel could be safely administered to women with recurrent ovarian cancer. Correlative biomarker and imaging studies of anti-angiogenesis targeting, pharmacokinetics (PK) and preliminary efficacy were additional objectives. Methods: Eligible patients had measurable, recurrent disease with no more than 3 prior chemotherapeutic regimens. Study design was a “lead-in” phase I trial; cycle 0, administered aflibercept IV as a single agent in 1 of 3 dose levels (2, 4, or 6 mg/kg) in a 3+3 design. Aflibercept was given in subsequent cycles with docetaxel (75 mg/m2); each cycle was 21 days. Correlative studies in cycle 0 were: PK (single agent), circulating endothelial cells and precursors (CEC, CEP), and imaging FDG-PET, DCE-MRI (baseline, day 2 and day 21). Efficacy evaluation (RECIST) was conducted q2 cycles of combination therapy. Results: Nine patients were recruited, 3 at each dose level. All are evaluable. No DLTs were observed in cycles 0 and 1; The most common hematological toxicities were myelosuppression (1 Grade 4 ANC) and anemia (Grade 2). Non-hematological toxicities (Gr 3) included headache, hypertension, fatigue and ulceration. One patient each with hypertension and ulceration lead to treatment discontinuation after 4 and 13 cycles, respectively. FDG-PET defined SUVmax in target lesions within 25% of baseline in 7 patients; 2 others had >25% increase at 48 hours post treatment. CECs, CEPs, DCE-MRI and PK are being analyzed. Confirmed PR was observed in 2 (22%) with 1 additional near PR. Median number of cycles: 5 (range 3–15). All have now progressed, median time to progression: 15 weeks. Conclusions: Aflibercept can be safely administered at 6 mg/kg with docetaxel repeatedly in this population of recurrent ovarian cancer patients. Preliminary efficacy supports phase II study, which is ongoing. No significant financial relationships to disclose.

3-Hour infusion of single-agent paclitaxel for recurrent ovarian cancer

2001 ◽  
Vol 6 (3) ◽  
pp. 128-131 ◽  
Author(s):  
H. Ishikawa ◽  
T. Nakanishi ◽  
A. Nawa ◽  
Y. Suzuki ◽  
K. Kuzuya
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Recurrent Ovarian Cancer

Second-line randomized trials in epithelial ovarian cancer

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 59-66 ◽  
Author(s):  
J. B. Vermorken
Keyword(s):  
Ovarian Cancer ◽  
Randomized Trials ◽  
Single Agent ◽  
Complete Response ◽  
Recurrent Ovarian Cancer ◽  
First Line ◽  
Symptomatic Disease ◽  
First Line Therapy ◽  
Line Therapy ◽  
Response To Chemotherapy

Important issues in the treatment of patients with recurrent ovarian cancer (ROC) are 1) to delay the time to symptomatic disease, 2) to reduce symptoms in case of symptomatic disease, 3) to optimize quality of life, and 4) to prolong overall survival. However, response assessment and recording of treatment-induced side effects in general get most attention. The likelihood of response to chemotherapy is directly proportional to the length of time between the end of primary chemotherapy and the date of recurrence. Also, the aggressiveness of the recurrence seems related to the prior biological pace of disease progression. For these reasons different disease categories have been identified, ie, platinum/taxane-refractory disease (progressive during first-line stabilization as best response), persistent disease (partial response to first-line therapy), platinum/taxane-resistant disease (clinical complete response [CCR] or no evidence of disease [NED] to/after first line and relapse <6 months), and platinum/taxane-sensitive disease (CCR or NED to/after first line and relapse >6 months). Randomized trials in these different categories did not show a benefit of maintenance or consolidation therapies after first-line therapy but did show differences in tolerability and efficacy (in platinum/taxane-sensitive disease) of different single agents and indicated that in specific circumstances combination chemotherapy is superior to single-agent chemotherapy. However, in all circumstances other aspects such as toxicity (and earlier experienced toxicity), clinical condition, convenience of administration, costs, and patient preference should be considered in the final selection of treatment

Sign in / Sign up

Export Citation Format

Share Document