scholarly journals Real-World Experience in Toxicity with Bevacizumab in Indian Cancer Patients

2021 ◽  
Vol 10 (02) ◽  
pp. 131-134
Author(s):  
Pratik P. Patil ◽  
Ranga R. Rangaraju ◽  
Waseem Abbas ◽  
Sunny Garg
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
North India ◽  
Age Group ◽  
Round Cell ◽  
Gastrointestinal Side Effects ◽  
Life Threatening ◽  
Grade 3 ◽  
Subacute Intestinal Obstruction

Abstract Background Bevacizumab, a humanized monoclonal antibody, known to block the binding of all known vascular endothelial growth factor-A isomers to their receptors, is used in solid cancers, especially in advanced settings where its role is proven to be stronger than localized stages. Furthermore, various studies have suggested that adding bevacizumab to first-line standard therapy in advanced solid cancers, such as colorectal cancer, lung cancer, ovarian cancer, renal cancer, and breast cancer, significantly prolongs progression-free survival, overall survival, and response rates. However, this ability is limited and variable in cancer subtype. The toxicity profile of bevacizumab is outspread, ranging from mild gastrointestinal side effects, proteinuria to life-threatening hemorrhagic tendency, ischemic thromboembolism, and intestinal perforation. However, it has never been studied in Indian subset of patients till date. Materials and Methods We performed an institutional retrospective study of 41 patients with a pathologically proven ovarian, colorectal, lung, mesothelioma, melanoma, round cell tumors, and GBMs who received bevacizumab (2.5 mg/kg/week [5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks]) with or without chemotherapy, between January 2016 and January 2019 at our center in North India. Results Forty-one patients, including 12 (29) advanced ovarian cancer, 12 (29) colon cancer, 10 (24) rectal cancer, 1 (2) appendicular cancer, 1 (2) mesothelioma, 1 (2) melanoma, 1 (2) desmoplastic round cell tumor, and 3 (7) GBM, were treated with bevacizumab. The incidence of arterial thrombus and hemorrhage was 2 and 10%, respectively, whereas venous thrombus and fistula were not seen and not related to age. No fatal adverse event was recorded. The global incidence of severe (grade 3/4) arterial hypertension (HTN) was 49%. It was safely managed in all cases, and no grade 4 (life-threatening complication) occurred. The incidence of severe HTN was significantly higher in elderly patients than in younger ones (72 vs. 40%), proteinuria was found to be more frequent in the younger age group as compared with older age group (7 vs. 3%). Also to note, the incidence of congestive heart failure and subacute intestinal obstruction was found in 5% of patients, wherein all four patients belonged to the older subgroup. Furthermore, Grade 3 hypersensitivity reaction was found in one patient in the younger subgroup which warranted immediate termination of bevacizumab.

Topotecan (T) and carboplatin (C) in the treatment of platinum sensitive relapsed ovarian cancer (ROC): Results of a multicenter phase I/II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5089-5089
Author(s):  
D. Koensgen ◽  
A. Belau ◽  
P. Klare ◽  
T. Steck ◽  
O. Camara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Remission Rate ◽  
Primary Standard ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Median Number ◽  
Hematological Toxicity ◽  
Platinum Sensitive ◽  
Grade 3

5089 Background: Despite of the effectiveness of radical surgery and first-line chemotherapy, most patients (pts) with advanced ovarian cancer will relapse. Paclitaxel (P) in combination with C as second-line treatment improves the outcome of pts with platinum-sensitive ROC in comparison to C monotherapy. Due to polyneuropathy and alopecia this regimen can not be offered to all pts. Therefore, other platinum-combinations are required. We conducted a phase I/II study to define the dose limiting toxicities (DLT) and the tolerability of combination therapy with T and C. Methods: Pts with platinum-sensitive ROC and primary standard therapy were stratified according to treatment-free interval (TFI): 6–12 months (A) and ≥12 months (B). Following dose regimens were analysed: T 1mg/m2/d1–3 + C AUC5/d3 and T 0.75 mg/m2/d1–3 + C AUC5/d3, q21d. DLT was based on the first 4 courses and defined as: CTC grade 3/4 hematological and grade 2 non-hematological toxicity (excepted alopecia, vomiting), treatment delay >7d. Primary endpoints were DLT and tolerability. Secondary endpoints were remission rate (RR) and progression-free survival (PFS). Results: From 06/04 to 08/05, 28 pts were enrolled, 26 pts (A:13 pts, B:13 pts) were eligible. Median age was 61.5 years. A total of 141 cycles were analysed, median number of cycles was 6 (range A:2–8, B:1–10). DLTs were: leucopenia (n = 5) and thrombocytopenia (n = 1). MTD was reached at dose: T: 0.75mg/m2 and C: AUC5. Overall, grade 3/4 hematologic toxicities (in% of all cycles), for (A) and (B) respectively, were: anemia 4% vs. 4%, leucopenia 34% vs. 13%, neutropenia 30% vs. 31%, thrombocytopenia 7% vs. 6%. Febrile neutropenia 4.3% vs. 0%. Darbepoetin alfa was given in 13.5% of all cycles. Overall, grade 3/4 non-hematologic toxicities were infrequent (< 5%). Overall RR (95% CI) was 50% (29.7–70.1) [A: 30.8% (0.1–61.1), B: 69.3% (38.7–90.9)]. Median follow-up was 5.8 mo, median PFS (95% CI) was 7.7 mo (1.3–9.4) [A: 6.2 (1.3–7.2), B: 8.0 (7.3–9.4)]. Median overall survival was not reached. Conclusions: TC is a feasible and effective chemotherapy regimen for platinum sensitive ROC. Tolerability is not associated to TFI. The recommended dose for subsequent studies is T:0.75 and C:AUC5. No significant financial relationships to disclose.

The Prognostic Impact of the Pathological Response to Neoadjuvant Dose-Dense Therapy for Ovarian Carcinoma

2017 ◽  
Vol 27 (9) ◽  
pp. 1850-1855 ◽  
Author(s):  
Takahiro Ebata ◽  
Mayu Yunokawa ◽  
Hiroshi Yoshida ◽  
Seiko Bun ◽  
Tatsunori Shimoi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factors ◽  
Tumor Cells ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Pathological Response ◽  
Prognostic Impact ◽  
Grade 3 ◽  
Dose Dense

ObjectiveThe aim of this study was to assess the use of the pathological response to neoadjuvant chemotherapy (NAC) for predicting disease prognosis in patients with advanced ovarian cancer who received neoadjuvant dose-dense weekly paclitaxel and carboplatin (dd-TC) therapy.MethodsWe retrospectively investigated patients with advanced epithelial ovarian, tubal, or peritoneal carcinoma treated at our hospital from July 2004 to October 2014. Patients received dd-TC therapy as NAC followed by interval debulking surgery (IDS). Specimens resected during IDS were divided into 4 groups based on pathological response: grade 1, most tumor cells appeared to be viable; grade 2a, most tumor cells had disappeared, whereas the remaining tumor cells were vacuolated or degenerated; grade 2b, small numbers of viable tumor cells were observed; and grade 3, small aggregations of macrophages were seen.ResultsSixty-eight patients were enrolled. The median number of NAC cycles was 3 (range, 2–6), and 51 patients (75.0%) achieved complete resection at IDS. Regarding pathological response, 7 (10.3%) patients were classified as grade 1, 11 (16.2%) as grade 2a, 46 (67.7%) as grade 2b, and 4 (5.9%) as grade 3. In univariate and multivariate analyses, grades 2b and 3 pathological responses were significant favorable prognostic factors for progression-free survival (P = 0.028; hazard ratio, 0.48; 95% confidence interval, 0.26–0.92).ConclusionsAlthough the pathological complete response rate to NAC was low in this study, both complete and good pathological responses to NAC might be favorable prognostic factors for PFS in patients with advanced ovarian cancer who receive dd-TC.

A phase 1b/2 study of napabucasin with weekly paclitaxel in advanced, previously treated platinum resistant ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5548-5548 ◽  
Author(s):  
Carlos Becerra ◽  
Agustin A. Garcia ◽  
John L. Hays ◽  
Michael W. Method ◽  
Stephen Lane Richey ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Dose Escalation Study ◽  
Clinical Safety ◽  
Platinum Resistant ◽  
Grade 3 ◽  
Expansion Cohort

5548 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, napabucasin plus weekly PTX was well tolerated. A phase II expansion cohort was opened for patients with platinum resistant ovarian cancer. Methods: Pts with advanced ovarian cancer who had disease progression either during or in the 6 months following platinum-based systemic therapy were enrolled. napabucasin was administered orally at a starting dose of 240, 480, or 500 mg twice daily with PTX 80 mg/m2 IV weekly on 3 of every 4 weeks. AEs were evaluated using CTCAE v4.03 and objective assessments were performed per RECIST 1.1 every 8 weeks. Results: A total of 98 pts were enrolled. The average number of prior lines of systemic treatment was 3.5, including prior taxane-based therapy in 100% of patients. Treatment was well tolerated. Related grade 3 adverse events occurring ≥ 5% of pts included diarrhea (12.2%) and vomiting (5.1%). Among pts who received RECIST evaluation (n = 76), the disease control rate (DCR, proportion with SD at 8 weeks + PR + CR) was 65%, and the objective response rate (ORR, PR+CR) was 20%, with complete response in 3 pts (4%). In all patients (ITT, n = 98), the median progression-free survival (mPFS) was 3.0 months and median overall survival (mOS) was 9.3 months. Conclusions: Clinical safety and encouraging signs of anti-cancer activity, including three complete responses, were observed in pts with pre-treated platinum resistant ovarian cancer who received treatment with napabucasin plus weekly PTX. Further clinical evaluation in controlled trials is warranted. Clinical trial information: NCT01325441.

Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study

2004 ◽  
Vol 22 (13) ◽  
pp. 2635-2642 ◽  
Author(s):  
Sabino De Placido ◽  
Giovanni Scambia ◽  
Giovanni Di Vagno ◽  
Emanuele Naglieri ◽  
Alessandra Vernaglia Lombardi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Randomized Study ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Significant Difference ◽  
Grade 3

Purpose Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. Patients and Methods To investigate whether topotecan (1.5 mg/m2 on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m2 administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. Results Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P = .83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. Conclusion The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

scholarly journals Bevacizumab Combined with Platinum–Taxane Chemotherapy as First-Line Treatment for Advanced Ovarian Cancer: Results of the NOGGO Non-Interventional Study (OTILIA) in 824 Patients

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4739
Author(s):  
Jalid Sehouli ◽  
Alexander Mustea ◽  
Guelten Oskay-Özcelik ◽  
Maren Keller ◽  
Rolf Richter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Figo Stage ◽  
Gynecology And Obstetrics ◽  
Grade 3 ◽  
One Year ◽  
Oncology Practice ◽  
Taxane Chemotherapy

In the single-arm non-interventional OTILIA study, patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IIIB–IV ovarian cancer received bevacizumab (15 mg/kg every 3 weeks for up to 15 months) and standard carboplatin–paclitaxel. The primary aim was to assess safety and progression-free survival (PFS). Subgroup analyses according to age were prespecified. The analysis population included 824 patients (453 aged <70 years, 371 aged ≥70 years). At data cutoff, the median bevacizumab duration was 13.8 months. Grade ≥3 adverse events (AEs), serious AEs, and AEs leading to bevacizumab discontinuation were more common in older than younger patients, whereas treatment-related AEs were less common. Median PFS was 19.4 months, with no clear difference according to age (20.0 vs. 19.3 months in patients <70 vs. ≥70 years, respectively). One-year OS rates were 92% and 90%, respectively. Mean change from baseline in global health status/quality of life showed a clinically meaningful increase over time. In German routine oncology practice, PFS and safety were similar to reported randomized phase 3 bevacizumab trials in more selected populations. There was no notable reduction in effectiveness and tolerability in patients aged ≥70 years; age alone should not preclude use of bevacizumab-containing therapy. ClinicalTrials.gov: NCT01697488.

scholarly journals Tolerance of weekly metronomic paclitaxel and carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer patients who are unlikely to tolerate 3 weekly paclitaxel and carboplatin

2016 ◽  
Vol 05 (02) ◽  
pp. 063-066 ◽  
Author(s):  
S. B. Dessai ◽  
S. Chakraborty ◽  
T. V.S. Babu ◽  
S. Nayanar ◽  
A. Bhattacharjee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Response Rates ◽  
Weekly Paclitaxel ◽  
Life Threatening ◽  
Radiological Response ◽  
Grade 3

Abstract Objective: There are little data regarding safety and effectiveness of neoadjuvant chemotherapy (NACT) in patients who are considered unfit for receiving 3 weekly paclitaxel and carboplatin. The aim of this study was to examine the toxicity and response rates of weekly paclitaxel and carboplatin as NACT in such cohort of patients. Methods: Study population included advanced ovarian cancer patients who were unlikely to tolerate 3 weekly paclitaxel and carboplatin and hence received weekly paclitaxel (80 mg/m 2) and carboplatin AUC-2 as NACT. The data regarding the baseline characteristics, chemotherapy tolerance, completion rates, toxicity (Common Terminology Criteria for Adverse Events version 4.02), and radiological response rates are presented. SPSS version 16 was used for analysis. Descriptive statistics is presented. Results: Eleven patients received this schedule. Nine patients completed nine cycles of NACT. Except one, all patients completed NACT with an average relative dose intensity of >0.8. There was no chemotherapy-related mortality. Grade 3-4 life-threatening complications were seen in two patients. The post NACT response rate was 100%. Conclusions: Weekly paclitaxel and carboplatin chemotherapy is safe and efficacious in patients who are unsuitable for 3 weekly paclitaxel and carboplatin chemotherapy schedules.

Mature results of a phase II study of intraperitoneal topotecan as consolidation therapy in ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5570-5570
Author(s):  
T. W. Malpass ◽  
K. McGonigle ◽  
M. Roberston ◽  
P. Weiden ◽  
H. G. Muntz
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Abdominal Distension ◽  
Consolidation Therapy ◽  
Hematopoietic Growth Factors ◽  
Peritoneal Cancer ◽  
Second Look ◽  
Grade 3

5570 Background: Previous studies with intraperitoneal (IP) topotecan have shown 20 mg/m2 to be well tolerated. This study evaluated the feasibility, safety, and effectiveness of IP topotecan as consolidation therapy for ovarian cancer. Methods: Patients with stage III/IV ovarian (or primary peritoneal) cancer in clinical complete response after cytoreduction and IV chemotherapy with carboplatin and paclitaxel who had benign findings or minimal persistent disease (<= 1 cm diameter) documented at second-look surgery were eligible. IP topotecan 20 mg/m2 was administered once every 21 days for 4 to 6 cycles. Dose reduction was based on grade 3–4 toxicities. Hematopoietic growth factors were used at the discretion of the treating physician. Results: Twenty patients were enrolled (18 ovarian and 2 peritoneal cancers). Sixteen patients received 4 cycles, 3 patients received 6 cycles, and 1 patient withdrew by personal request after 1 cycle. Of the total 83 cycles, 10 (12%) were delayed due to slow recovery of neutropenia, and 22 (27%) were administered with does reductions due to prior grade 3–4 myelosuppression. Mean delivered dose was 18 mg/m2. Major toxicities included episodes of neutropenia (6 grade 3; 3 grade 4) and thrombocytopenia (7 grade 3; 2 grade 4). Filgrastim was administered to 75% of patients in 51 (61%) cycles, and epoetin alfa was administered to 30% of patients in 20 (24%) cycles. Other adverse events (grade 1 or 2) that occurred in approximately half of patients included nausea and abdominal distension. Median progression-free survival was 24 months from second-look surgery (Kaplan-Meier, 95% CI 14–34 months). Sixteen patients (80%) are alive after median of 42 months from second look surgery (range, 29 to 62 months), with 4.5 year estimated overall survival of 84% (95% CI 68–100%) measured from original diagnosis. Conclusion: Consolidation IP topotecan 20 mg/m2 every 3 weeks for 4–6 cycles is feasible and well tolerated. Progression-free and overall survival in this pilot study compare favorably with results expected for advanced ovarian cancer. Future investigation of IP topotecan is warranted, both as consolidation therapy and salvage therapy for advanced ovarian cancer. No significant financial relationships to disclose.

scholarly journals A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer

2021 ◽  
Author(s):  
Shunji Takahashi ◽  
Munetaka Takekuma ◽  
Kenji Tamura ◽  
Kazuhiro Takehara ◽  
Hiroyuki Nomura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Liposomal Doxorubicin ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Japanese Patients ◽  
Pharmacokinetic Analysis ◽  
Dependent Manner ◽  
Drug Concentrations ◽  
Grade 3

Abstract Background Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. Methods This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1. Results Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 reductions in neutrophil count, but these events were generally manageable through dose reduction and/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose-dependent manner. The overall response rate was 27.8%. Conclusions Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1 mg/m2 once every 21 days. Clinical trial registration number: JapicCTI-163164

scholarly journals Successful treatment of advanced ovarian cancer with anlotinib: a case report

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052097682
Author(s):  
Ping Zhang ◽  
Liangliang Ma ◽  
Xiaojie Wang ◽  
Ruijie Zhang ◽  
Yuting Dong
Keyword(s):  
Ovarian Cancer ◽  
Mild Hypertension ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Inhibit Tumor Growth ◽  
Free Survival ◽  
Multiple Line ◽  
Serum Ca125

Ovarian cancer remains the most lethal gynecological malignant tumor, with relapse occurring in approximately 70% of advanced cases. Anlotinib is an oral small-molecule multi-targeted tyrosine kinase inhibitor that can resist neoangiogenesis and inhibit tumor growth. Previous research demonstrated clinical antitumor activity of anlotinib in various cancers. We report the case of an elderly woman with advanced ovarian cancer who received anlotinib after failure of multiple-line chemotherapy. A partial response was observed after six cycles of anlotinib monotherapy, with a reduction in the size of the metastases and significantly decreased serum CA125 levels from 1832.7 U/mL to 118.7 U/mL. She continued to take anlotinib, with a progression-free survival time of more than 4 months. Only mild hypertension was observed during the treatment. Anlotinib monotherapy may be a novel therapeutic option for patients with advanced ovarian cancer.

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