Olaparib dose re‐escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series

5580 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which have been approved for the treatment of recurrent and newly diagnosed glioblastoma by the FDA. TTFields act by delivering intermediate frequency alternating electric fields to the tumor, predominantly by disrupting the formation of the mitotic spindle during metaphase. INNOVATE was the first trial testing TTFields (200kHz) in ovarian cancer patients. Methods: Thirty-one recurrent, platinum-resistant, unresectable ovarian cancer patients were enrolled in the INNOVATE trial and treated with TTFields in combination with weekly paclitaxel. The primary endpoint was treatment emergent adverse events. Secondary endpoints included progression free-survival, overall survival and radiological response rate. Results: The median age was 60 (range – 45-77), most patients (77%) had serous histology. 52% had an ECOG score of 0. The median number of prior chemotherapy regimens was 4.1 (range 1-11). All patients were platinum-resistant, and 97% of patients received prior taxane-containing regimens. Ten (32%) patients suffered from serious adverse events (SAEs) during the study, none were related to TTFields. Of all reported SAEs, 31% were related to gastrointestinal disorders (ileus, jaundice and ascites) and 31% were respiratory events (dyspnea, pleural effusion and pulmonary embolism). Only one SAE which, related to the tumor, led to permanent discontinuation of the device. Most patients were reported to have mild-moderate, TTFields-related skin irritation, out of whom only two patients (6.4%) had severe-grade events. The median PFS was 8.9 months (95% CI 4.7, NA). Of the evaluable tumors, 25% had partial response and another 46.4% stable disease – a clinical benefit of 71.4%. Six patients (19.4%) had a CA 125 response, translating into a decrease of 50% or more in serum levels. The median OS was not reached. Conclusions: TTFields concomitant to weekly paclitaxel are tolerable and safe in heavily pre-treated platinum-resistant ovarian cancer ovarian cancer patients. These data support further clinical testing of TTFields with chemotherapy in ovarian cancer. Clinical trial information: NCT02244502.

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The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China

Journal of Ovarian Research ◽

10.1186/s13048-021-00803-2 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jing Ni ◽

Xianzhong Cheng ◽

Qian Zhao ◽

Zhiqin Dai ◽

Xia Xu ◽

...

Keyword(s):

Ovarian Cancer ◽

Partial Response ◽

Adverse Events ◽

Cancer Patients ◽

Real World ◽

Parp Inhibitor ◽

Objective Response ◽

Single Center ◽

Real World Data ◽

Platinum Based Chemotherapy

Abstract Background Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China. Methods Patients treated with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. Results Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI = 0.060–0.759) and disease control rate (DCR) of 50% (95%CI = 0.140–0.861) in the exploratory multi-line monotherapy group. The most common AEs were nausea, thrombocytopenia, and anemia. Grade 3–4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. Conclusion It is feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population can acquire promising efficacy and tolerance. This is the first real-world data about niraparib in ovarian cancer patients with available HRD status from China.

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Comorbidities and Adverse Events in Advanced and Recurrent Ovarian Cancer Patients in France

Annals of Oncology ◽

10.1093/annonc/mdu338.38 ◽

2014 ◽

Vol 25 ◽

pp. iv317

Author(s):

O. Le Saux ◽

A. Taylor ◽

V. Chia ◽

D. Pillas ◽

G. Kafatos ◽

...

Keyword(s):

Ovarian Cancer ◽

Adverse Events ◽

Cancer Patients ◽

Recurrent Ovarian Cancer

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Significance of changes in serum CA125 level on overall survival in ovarian cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16546 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16546-e16546

Author(s):

S. Williams ◽

D. Gupta ◽

S. Dahlk ◽

K. E. Dzike ◽

G. M. Lambert ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Case Series ◽

Stage Iv ◽

Time Interval ◽

Prognostic Impact ◽

Baseline Serum ◽

Serum Ca125 ◽

The Impact

e16546 Background: The role of baseline serum CA125 as a prognostic indicator in ovarian cancer is well documented. However, little is known about the impact of change in CA125 on survival after 3 months of therapy. We conducted survival analysis to answer the question “what is the prognostic impact of change in serum CA125 after 3 months of therapy in ovarian cancer?” Methods: A case series of 170 ovarian cancer patients treated at Cancer Treatment Centers of America between Jan 01 and May 06. Based on CA125 levels at baseline and 3 months, patients were classified into 4 groups: 1) Normal (0–35U/ml) at baseline and three months; 2) High (>35U/ml) at baseline, normal at three months; 3) Normal at baseline, high at 3 months; 4) High at baseline and three months. Kaplan Meier method was used to calculate survival across the 4 categories, which was defined as the time interval between date of patient visit at 3 months from first visit and date of death from any cause or date of last contact. Results: Of 170 patients, 36 were newly diagnosed while 134 had received prior treatment. 25 had stage I disease at diagnosis, 15 stage II, 106 stage III and 14 stage IV. The median age at presentation was 54.2 years (range 23.1 - 82.5 years). At baseline, 31 patients had normal (0–35U/ml) serum CA125 levels while 138 had high (>35U/ml) levels. At 3 months, 59 had normal while 111 had high levels. In this cohort, patients with a reduced CA125 at 3 months (stratum 2) had a significantly better survival than those with increased CA125 at 3 months (stratum 3). Patients with normal values of CA125 at both baseline and 3 months (stratum 1) had the best overall survival. Conclusions: These data show that reduction in CA125 after 3 months of therapy is associated with better overall survival in ovarian cancer. Patients without a significant decline in CA125 after 3 months of therapy have a particularly poor prognosis. [Table: see text] No significant financial relationships to disclose.

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Adverse Events Associated With Complementary and Alternative Use in Ovarian Cancer Patients

Obstetrical & Gynecological Survey ◽

10.1097/01.ogx.0000438239.12283.98 ◽

2013 ◽

Vol 68 (11) ◽

pp. 741-742

Author(s):

Erin S. Sweet ◽

Leanna J. Standish ◽

Barbara A. Goff ◽

M. Robyn Andersen

Keyword(s):

Ovarian Cancer ◽

Adverse Events ◽

Cancer Patients ◽

Complementary And Alternative

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The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China

10.21203/rs.3.rs-101839/v1 ◽

2020 ◽

Author(s):

Jing Ni ◽

Xianzhong Cheng ◽

Qian Zhao ◽

Zhiqin Dai ◽

Xia Xu ◽

...

Keyword(s):

Ovarian Cancer ◽

Partial Response ◽

Adverse Events ◽

Cancer Patients ◽

Real World ◽

Parp Inhibitor ◽

Objective Response ◽

Advanced Ovarian Cancer ◽

Real World Data ◽

Platinum Based Chemotherapy

Abstract BackgroundNiraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD) positive. We present real-world experience from China. MethodsPatients with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. ResultsTwenty-two patients all received niraparib at an bolus of 200mg/d. 50% of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI=0.060-0.759) and DCR of 50% (95%CI=0.140-0.861) in the exploratory multi-line monotherapy group. Commonly AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. ConclusionIt is feasible for patients received a bolus of 200mg/d in Chinese population with promising efficacy and well tolerated. This is first real world data about niraparib in ovarian cancer patients with HRD status from China.

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Adverse Events as a Potential Clinical Marker of Antitumor Efficacy in Ovarian Cancer Patients Treated With Poly ADP-Ribose Polymerase Inhibitor

Frontiers in Oncology ◽

10.3389/fonc.2021.724620 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jing Ni ◽

Xianzhong Cheng ◽

Rui Zhou ◽

Qian Zhao ◽

Xia Xu ◽

...

Keyword(s):

Ovarian Cancer ◽

Adverse Events ◽

Cancer Patients ◽

Brca Mutation ◽

Parp Inhibitor ◽

Antitumor Efficacy ◽

Categorical Variables ◽

Rank Test ◽

Hematological Toxicity ◽

Clinical Marker

BackgroundPARP inhibitor (PARPi) is an important progress in ovarian cancer treatment. The available evidence suggests that BRCA mutation and homologous recombination deficiency (HRD) are effective biological markers for PARPi. Here we investigated the relationship between adverse events (AEs) and efficacy of PARPi in ovarian cancer patients.MethodsSeventy-eight patients with ovarian cancer patients underwent Olaparib and Niraparib from July 2018 to July 2020 were analyzed. AEs were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Chi-square test or fisher exact tests was performed to observe the association between categorical variables. Logistic regression analysis was conducted to investigate the independent variables for disease control response (DCR). Progression-free survival (PFS) was compared between AEs variables by log-rank test.ResultsPatients with AEs in the first one week had a higher DCR compared with those after one week (86.11% versus 60.98%, p=0.013). Patients with serious AEs (SAEs) had a significantly higher DCR (81.40% versus 60.60%, p=0.045). There were associations between anemia and DCR in both occurrence (79.63% versus 56.52%, p=0.037) and grade (100% versus 73.17%, p=0.048). The median PFS of patients with hematological toxicity was longer than that of patients with no-hematological toxicity (30 versus 20 weeks, p=0.047). Patients with hematological toxicity within four weeks had prolonged median PFS than those with hematological toxicity after four weeks (40 versus 22 weeks, p=0.003).ConclusionsThe early presence of AEs and SAEs in hematological toxicity of PARPi were related to the antitumor efficacy, which might be a valid and easily measurable clinical marker in ovarian cancer patients.

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THE ROLE OF CORTICOSTEROIDS IN ADULT RESPIRATORY DISTRESS SYNDROME CAUSED BY VIRIDANS GROUP STREPTOCOCCI BACTEREMIA IN NEUTROPENIC PATIENTS

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2014.055 ◽

2014 ◽

Vol 6 (1) ◽

pp. e2014055 ◽

Cited By ~ 1

Author(s):

Abraham Tareq Yacoub ◽

Lysenia Mojica ◽

Lily Jones ◽

Andrea Knab ◽

Sally Alrabaa ◽

...

Keyword(s):

Respiratory Failure ◽

Adverse Events ◽

Cancer Patients ◽

Hematologic Malignancy ◽

Case Series ◽

Cancer Center ◽

Viridans Streptococci ◽

Gram Positive ◽

Neutropenic Patients ◽

Gram Positive Cocci

IntroductionDuring the last decades, gram-positive bacteremia has increased dramatically. Gram-positive cocci are the most frequent cause of nosocomial bloodstream infections. Among Gram-positive cocci, Viridans streptococci are a common cause of bacteremia in cancer patients with neutropenia, causing serious complications such as pneumonia, septic shock, and ARDS [1-6]. We present a series of cases of VGS bacteremia complicated with ARDS; early initiation of corticosteroids resulted in complete recovery.Materials and MethodsA retrospective chart review of patients with hematologic malignancy diagnosed with VGS bacteremia admitted to the Moffitt Cancer Center in Tampa, Florida between 1/1/2001 and 4/1/2012 was completed. Data was collected about respiratory symptoms, diagnosis of adult respiratory syndrome, results of blood cultures, medications received and outcome.ResultsIn this study, 70 cases of VGS bacteremia in neutropenic patients were reviewed. The most common adverse event of VGS bacteremia in this group of patients is the development of serious pulmonary complications such as ARDS. In our study, 7 patients developed ARDS. The most common identifies streptococcal species was Streptococcus mitis, isolated in 4 of 7 patients. All 7 patients received corticosteroids early with the onset of respiratory failure. The most commonly prescribed regimen was methylprednisolone 60 mg intravenously every 12 hour for an average of 3 days. All patients received comparable supportive care, appropriate antibiotics, ventilation and hemodynamic support. All patients (100 %) recovered from respiratory failure after receiving corticosteroids. There were no significant adverse events attributable to steroids use.ConclusionStreptococcus mitis is the species most frequently isolated from the patients who have developed ARDS from Streptococcus viridans bacteremia. Our data suggest that the early administration of corticosteroids to neutropenic patients who develop early signs of respiratory failure with VGS bacteremia can prevent the progression of ARDS and improve mortality. Moderate doses of steroids with short duration of administration were not associated with significant adverse events in our case series. While the use of corticosteroids in this setting has been described in the literature since the early 1990s, there remains a scarcity of data and our study help shed some light on this area. Moreover there is little recognition among clinicians of the association between ARDS and VGS bacteremia (particularly mitis species in neutropenic cancer patients) and thus this treatment modality is used late in the course of illness which may reduce benefit. Further studies are warranted to validate these findings and to further examine the utility of preemptive use of corticosteroids in cancer patients who develop VGS bacteremia, in regards to ARDS incidence reduction.

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