scholarly journals Study of efficacy and safety of adjuvant intraperitoneal chemotherapy in carcinoma ovary

2016 ◽  
Author(s):  
Varun Goel ◽  
Sajjan Singh ◽  
Vineet Talwar ◽  
Pankaj Goyal ◽  
Amitabh Upadhyay ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Indian Subcontinent ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Pharmacokinetic Data ◽  
Renal Complication ◽  
Grade 3 ◽  
Carcinoma Ovary

Background: The benefit of administering chemotherapy directly into the peritoneal cavity is supported by preclinical, clinical and pharmacokinetic data. In view of paucity of data from the Indian subcontinent, we decided to study the response and tolerability of intraperitoneal (I/P) chemotherapy in carcinoma ovary in Indian population. Methods: In this observational study, from March 2013 to June 2015, the efficacy and tolerability of adjuvant I/P chemotherapy in optimally cytoreduced stage III epithelial ovarian cancer patients were assessed. Treatment consisted of 135 mg/m2 of i.v. paclitaxel over a 3-hours period on day 1 followed by AUC 5 carboplatin i.v. on day 2 and 60 mg/m2 of i.p. paclitaxel on day 8 every 3 weekly for six cycles. Results: Total 50 patients were enrolled. The median age of patients was 53 yrs (32 yrs – 67 yrs). Out of a total of 240 I/P cycles, 225 cycles (93%) were completed. 30 patients (75%) received all the 6 cycles by IP route, 6 patients completed 5, 3 patients completed 4 cycles and 1 completed 3 I/P cycles. 4 Out of 30 patients who completed all 6 cycles of I/P chemotherapy, had one or more adjustment including delay while in 3 patients (7.5%) dose had to be reduced. after median follow up of 14 months, 8 patients (12.5%) had local or systemic recurrence, 2 patients (5%) had progression during treatment and died due to disease. median progression free survival not reached yet. One patients had vaginal leak. Catheter block was seen in five cases. Two cases had needle displacement and extravasations of drug around the port chamber. 6 patients had severe abdominal pain and cramp (grade 3) after infusion of saline. Hematologic toxicity was evaluated in all patients and in all cycles. Grade 3 or 4 Leucopenia was experienced by 25 patients (50%) but Febrile Neutropenia occurred in only 5 (10%) patients. Grade 3 or 4 anemia occurred in 17 (42.5%) and grade 3 or 4 thrombocytopenia was experienced by 6 patients (15%). Renal complication present in 3 patients (7.5%) and transient transfusion reaction developed in 5 patients. mucositis present in 21 patients. Conclusions: Adjuvant I/P chemotherapy in optimally cytoreduced epithelial ovarian cancer is active and well tolerated in Indian patients.

scholarly journals Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: ROSiA Single-Arm Phase 3B Study

2016 ◽  
Vol 27 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Amit M. Oza ◽  
Frédéric Selle ◽  
Irina Davidenko ◽  
Jacob Korach ◽  
Cesar Mendiola ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Single Agent ◽  
Clinical Signs ◽  
Progression Free Survival ◽  
Gynecology And Obstetrics ◽  
Common Grade ◽  
History Of ◽  
Grade 3

ObjectiveThe aim of this study was to assess the safety and efficacy of extending bevacizumab therapy beyond 15 months in nonprogressive ovarian cancer.Patients and MethodsIn this multinational prospective single-arm study (ClinicalTrials.gov NCT01239732), eligible patients had International Federation of Gynecology and Obstetrics stage IIB to IV or grade 3 stage I to IIA ovarian cancer without clinical signs or symptoms of gastrointestinal obstruction or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the preceding 6 months. Prior neoadjuvant chemotherapy was permitted. After debulking surgery, patients received bevacizumab 15 (or 7.5) mg/kg every 3 weeks (q3w) with 4 to 8 cycles of paclitaxel (investigator’s choice of 175 mg/m2 q3w or 80 mg/m2 weekly) plus carboplatin AUC 5 to 6 q3w. Single-agent bevacizumab was continued until progression or for up to 24 months. The primary end point was safety.ResultsBetween December 2010 and May 2012, 1021 patients from 35 countries began study treatment. Bevacizumab was administered at 15 mg/kg in 89% of patients and for more than 15 months in 53%. Median follow-up duration was 32 months (range, 1–50 months). The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%). The most common grade 3 or higher-grade adverse events were neutropenia (27%) and hypertension (25%). Bevacizumab was discontinued because of proteinuria in 5% of patients and hypertension in 3%. Median progression-free survival (PFS) was 25.5 months (95% confidence interval, 23.7–27.6 months).ConclusionExtended bevacizumab demonstrated increased incidences of proteinuria and hypertension compared with 12 or 15 months of bevacizumab in previous trials, but these rarely led to bevacizumab discontinuation. Median PFS is the longest reported for frontline bevacizumab-containing therapy. The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safety.

Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM) Patients with Dialysis-Dependent Renal Failure Is Effective but Carries High Rates of Toxicity.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 954-954 ◽  
Author(s):  
Lisa Chodirker ◽  
Joseph R. Mikhael ◽  
Keith Stewart ◽  
Andrew Winter ◽  
Donna E. Reece ◽  
...  
Keyword(s):  
Renal Failure ◽  
Survival Data ◽  
Progression Free Survival ◽  
High Dose ◽  
Hematologic Toxicity ◽  
High Dose Dexamethasone ◽  
Cd34 Cells ◽  
Common Grade ◽  
Grade 3

Abstract Background: Studies have shown ASCT to be feasible in MM patients (pts) with renal impairment but there are limited data supporting this approach in pts with severe dialysis-dependent renal failure. Patients and Methods: This is a single institution retrospective review of all MM pts who were receiving regular dialysis support at the time of ASCT. Pts with light chain amyloidosis were excluded. Results: From 1998–2006, 22 hemodialysis patients underwent ASCT at our institution. Median age at transplant was 54.3 years (range, 39.4–64.7); 17(77%) pts were male; 17(76%) Salmon Durie stage II–IIIB . MM subtypes: light chains only 9(41%), IgG 8(36%), IgA 4(13%), IgD 2(9%). All pts received high-dose dexamethasone (DEX)-based induction therapy (VAD or DEX alone). High dose therapy consisted of Melphalan (MEL) 200 mg/m2 in 18 pts and MEL 140 mg/m2 in 3 pts. A median of 5.87 X 106 (range, 2.47–51.0) CD34+ cells/kg were collected using cyclophosphamide 2.5 g/m2 + GCSF 10ug/kg/day. Median days to discharge were 19 (range, 14–59). Hematologic toxicity: Of 20 pts with transfusion data available, 14(70%) required RBC and 18(90%) platelet transfusions. Median time to engraftment for neutrophils was 11 days (range, 9–14) and for platelets 13 days (range, 8–17). All patients developed febrile neutropenia. Non-hematologic toxicity (data available in 21 pts): cardiac 13(62%) (arrhythmias, myocardial infarction, CHF), hypotension 6(29%), neurologic 6(29%)(seizure, altered sensorium), infections 6(29%), diarrhea 6(29%), electrolyte imbalances 4(19%) and bleeding 3(14%). Most common grade 3–4 toxicities included mucositis 17(81%), cardiac 12(57%)(most due to atrial arrhythmias), bleeding 3(14%)(epistaxis, hematemesis, tissue hematomas) and infections 3(14%)(CMV, bacteremia, Candidemia). Transplant related mortality (TRM) was 13.6% (3/22) with causes of death including disseminated candidiasis (2) and CMV infection. Responses: Partial responses (PR) were achieved in 18/22 pts. Progression free survival (PFS) from transplant was 22.3 months (95% CI 15–45.6). Three pts (13%) became dialysis-independent (all within 30 days post-transplant). At a median follow-up of 29.6 months (range 0.8–79.6), 10/22 (45%) of patients are alive. Estimated median overall survival from date of transplant was 60 months (95%CI 20.2–79.6) with a 5-year survival probability of 53.2%. Discussion: ASCT in dialysis-dependent MM pts achieves response rates and survival data comparable to that of non-dialysis populations. However, it carries increased toxicity, prolonged median days to discharge (19 days vs. institutional mean of 14 days) and a higher TRM (13.6% vs. institutional mean of 1.6%). The higher rates of cardiac and neurological toxicities enforce the need for pre-transplant identification of pts with co-morbidities, for consideration of dose reduction and risk factor optimization.

Consolidation Therapy with Subcutaneous (SC) Alemtuzumab After Fludarabine and Rituximab (FR) Induction Therapy Improves the Complete Response (CR) Rate in Chronic Lymphocytic Leukemia (CLL) and Eradicates Minimal Residual Disease (MRD) but Is Associated with Severe Infectious Toxicity: Final Analysis of CALGB Study 10101.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 210-210
Author(s):  
Thomas S Lin ◽  
Kathleen A Donohue ◽  
John C. Byrd ◽  
Margaret S Lucas ◽  
Eva Hoke ◽  
...  
Keyword(s):  
Residual Disease ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Consolidation Therapy ◽  
Varicella Zoster ◽  
Grade 3

Abstract Abstract 210 Background: Alemtuzumab (Campath-1H) is approved for the treatment of CLL. CALGB sought to determine whether alemtuzumab can improve the CR rate and eradicate MRD after induction chemoimmunotherapy by performing a phase II study administering FR followed by alemtuzumab consolidation to previously untreated, symptomatic CLL patients (pts). We previously reported preliminary toxicity data (Lin et al. ASH 2007) and now report final toxicity and response data. Methods: Pts received fludarabine 25 mg/m2 IV on days 1–5, and rituximab 50 mg/m2 IV on day 1, 325 mg/m2 on day 3, and 375 mg/m2 on day 5 of cycle 1 and then only on day 1 of cycles 2–6, repeated every 28 days for up to 6 cycles. Four months after the last fludarabine dose, pts with stable (SD) or responsive disease by NCI 96 criteria received SC alemtuzumab 3 mg on day 1, 10 mg on day 3, and 30 mg on day 5, and then thrice weekly thereafter for 6 weeks (18 total doses). Pts received standard Pneumocystis (PCP) and Varicella zoster virus prophylaxis and were monitored weekly by PCR for Cytomegalovirus (CMV) viremia. When unacceptable serious infectious toxicity was noted in pts who received alemtuzumab after achieving CR from FR induction, the study was amended so that only PR or SD pts received alemtuzumab after FR. Results: Median age of pts (n=102) was 61 years (range, 23–82), 74% were male, and 30% were Rai stage III/IV. FR was well tolerated; 93% of pts received at least 3 cycles, and 77% completed all 6 cycles. Overall, complete and partial response (OR, CR, PR) rates after FR induction were 90%, 29% and 61%, and 15% were MRD negative by flow cytometry. Fifty-eight pts received alemtuzumab, and 42 (72%) completed the planned 6 weeks of therapy. OR, CR, and PR rates after alemtuzumab (n=58) were 91%, 66% and 26%, and 50% were MRD negative. Twenty-eight of 45 pts (62%) in PR after FR who received alemtuzumab attained CR. Of 11 pts in CR after FR who received alemtuzumab, 5 were MRD negative prior to consolidation and 3 of the other 6 converted to MRD negative afterwards. By intent-to-treat for all patients enrolled, OR, CR, and MRD negativity were attained by 90%, 57% and 42% of pts. With a median follow up of 34 months, median progression free survival (PFS) was 37 months (95% CI, 33–43 months); PFS was 73% and overall survival (OS) 86% at 2 years. Two-year PFS (76% vs 70%, p=0.54) and OS (84% vs 88%, p=0.89) were similar for pts who did and did not receive alemtuzumab. Similarly, there were no differences in PFS or OS among the 30 pts in CR after FR whether or not they received alemtuzumab, although the numbers were small. Grade 3–4 neutropenia and thrombocytopenia were observed in 43% and 19% of pts during alemtuzumab therapy. Grade 3–4 non-hematologic toxicity was observed in 41% of pts, including 19% infections and 19% febrile neutropenia, during alemtuzumab therapy. As we previously reported, 5 pts in CR after FR who received alemtuzumab died from infections (viral meningitis, Listeria meningitis, Legionella pneumonia, CMV and PCP pneumonia), and one pt in PR after FR who received alemtuzumab died of Epstein-Barr (EBV) viremia without evidence of EBV lymphoma. These grade 5 toxicities occurred both during and for up to 7 months after alemtuzumab therapy. Conclusions: Alemtuzumab consolidation improved the CR and MRD negative rates after FR induction. However, alemtuzumab consolidation resulted in significant toxicity, particularly severe infections in pts who achieved a CR after FR induction. Longer follow up is needed to determine if the improved CR and MRD negative rates following alemtuzumab consolidation will eventually result in improved PFS or OS, especially among pts who achieved a PR after FR induction. Disclosures: Lin: GlaxoSmithkline: Consultancy, Employment; Genentech: Consultancy; Bayer: Consultancy. Off Label Use: Use of alemtuzumab as consolidation therapy. Byrd:Genentech: Consultancy, Research Funding. Link:Genentech: Consultancy. Rai:Genentech: Consultancy; Bayer: Consultancy.

Phase III Trial of Carboplatin Plus Paclitaxel With or Without Gemcitabine in First-Line Treatment of Epithelial Ovarian Cancer

2010 ◽  
Vol 28 (27) ◽  
pp. 4162-4169 ◽  
Author(s):  
Andreas du Bois ◽  
Jørn Herrstedt ◽  
Anne-Claire Hardy-Bessard ◽  
Hans-Helge Müller ◽  
Philipp Harter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Objective Response ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Term Survival ◽  
Advanced Epithelial Ovarian Cancer

PurposeOne attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non–cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.Patients and MethodsWe performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m2, respectively) with the same combination and additional gemcitabine 800 mg/m2on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.ResultsBetween 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).ConclusionThe addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.

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.

A phase-II study evaluatin safety and efficacy with weekly paclitaxel and carboplatin as a primary treatment for patients with advanced epithelial ovarian cancer (EOC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5077-5077 ◽  
Author(s):  
T. Safra ◽  
R. Bernstein Molho ◽  
D. Grisaru ◽  
S. Spigel ◽  
R. Geva ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Median Time ◽  
Phase Ii ◽  
Complete Response ◽  
Disease Recurrence ◽  
Primary Treatment ◽  
Safety And Efficacy ◽  
Grade 3

5077 Background: The standard chemotherapy for epithelial ovarian cancer (EOC) is carboplatin and paclitaxel every 3 weeks together with debulking surgery. This phase II trial was designed to determine the safety and efficacy of weekly carboplatin and paclitaxel treatment in patients with EOC. Methods: Between October 2003 to August 2005, 37 patients with stage Ic-IV epithelial ovarian, tubal or primary peritoneal carcinoma were enrolled into the study. Carboplatin at AUC=2 and paclitaxel at 80 mg/m2 were administered on days 1,8,15 of a 28-day cycle. Cytoreductive surgery was performed as primary treatment or after 3 cycles of neoadjuvant chemotherapy with additional chemotherapy after the surgery. Results: Median age of the patients was 67 (range 49–82). A mean of 6 chemotherapy cycles were administered (range 3–8). Median time of follow-up (from the beginning of chemotherapy until the last follow-up visit) was 15.57 months (range 0.2–26months). Thirty-three patients were evaluable for response. Complete response (CR) was observed in 26 patients (78.8%) and partial response (PR) in 7 (21.8%). By the time of data collection 13 out of 33 women (39.4%) experienced recurrent or persistent disease and one patient (3%) died from progressive disease during 2nd line chemotherapy. Since 20 out of 33 patients are still free of disease and all but one are still alive, it is too early to evaluate time to progression (TTP) and overall survival (OS). The median time to disease recurrence or progression after completion of primary chemotherapy was 7.5+ months (0.2–18.2+). As for toxicity; grade 3 and 4 neutropenia were seen in 5 (13.5%) and one patient (2.7%) respectively. There was no neutropenic fever. Other grade 3 and 4 hematologic toxicities were not observed. Six (16.2%) and 5 (13.5%) patients needed G-CSF and Epoetin support respectively. The main non-hematologic toxicities were alopecia (grade 1) and fatigue (grade 3 in two patients). Only two patients (5.4%) experienced grade 3 neuropathy. Conclusion: Weekly treatment with carboplatin and paclitaxel is feasible and well tolerated. The low toxicity rate especially regarding neuropathy warrants further investigation of this regimen. No significant financial relationships to disclose.

Genetic polymorphisms in hMSH2 and hMLH1 genes are associated with prognosis in epithelial ovarian cancer patients

2019 ◽  
Vol 29 (7) ◽  
pp. 1148-1155 ◽  
Author(s):  
Wengang Si ◽  
Shan Kang ◽  
Haiyan Sun ◽  
Juan Chen ◽  
Shiru Cao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Genetic Polymorphisms ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Allele Frequencies ◽  
Free Survival ◽  
Platinum Based Chemotherapy

ObjectiveDNA mismatch repair deficiency is not only thought to promote tumorigenesis but is also suggested to be associated with platinum-based chemotherapy treatment. In this study, we investigated the effects of two genetic polymorphisms in the hMSH2 and hMLH1 genes on the risk of epithelial ovarian cancer and the clinical outcome of patients treated with platinum-based chemotherapy.MethodsA case-control study was performed in 536 epithelial ovarian cancer patients and 532 control women. Genotypes of two polymorphisms were determined by the polymerase chain reaction/ligase detection reaction method. Pearson Chi-square test was used to evaluate genotype distributions and allele frequencies in the patients and controls. Kaplan-Meier survival curves, and univariate and multivariate Cox regression models were used to analyze the effect of polymorphisms on patients’ prognoses.ResultsThe genotype and allele frequencies of the rs2303428 and rs1800734 polymorphisms were not significantly different between the case and control groups. Compared with wild homozygous genotype, the presence of variant alleles (heterozygous and variant homozygous genotypes) did not affect the risk of developing epithelial ovarian cancer. However, survival analysis showed that the rs2303428 polymorphism was related to the prognosis of epithelial ovarian cancer patients. Compared with the TT genotype, patients carrying the C allele had a shorter progression-free survival during the 3- and 5-year follow-up (HR 1.41, 95% CI 1.07 to 1.87 and HR 1.56, 95% CI 1.12 to 2.16, respectively). For the rs1800734 polymorphism, the A allele may significantly increase patients’ progression-free survival compared with the GG genotype in the 5-year follow-up (HR 0.66, 95% CI 0.44 to 0.98).ConclusionOur research suggests that genetic polymorphisms in hMSH2 and hMLH1 may indicate the clinical progression of epithelial ovarian cancer patients treated with platinum-based chemotherapy.

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.

Phase III Randomized Trial of Intravenous Cisplatin Plus a 24- or 96-Hour Infusion of Paclitaxel in Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

2007 ◽  
Vol 25 (28) ◽  
pp. 4466-4471 ◽  
Author(s):  
David R. Spriggs ◽  
Mark F. Brady ◽  
Luis Vaccarello ◽  
Daniel L. Clarke-Pearson ◽  
Robert A. Burger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Peritoneal Cancer ◽  
Results Of Treatment ◽  
Grade 3 ◽  
To Receive

Purpose This study was undertaken to assess if prolonged paclitaxel administration in combination with cisplatin improves overall survival (OS) in epithelial ovarian cancer (EOC). Patients and Methods Eligible patients with suboptimal stage III or IV EOC, fallopian tube, or primary peritoneal cancer were randomly allocated to receive six cycles of cisplatin 75 mg/m2 and either paclitaxel 135 mg/m2 during 24 hours (arm 1) or paclitaxel 120 mg/m2 during 96 hours (arm 2). Results Planned accrual was 324 patients; 293 were enrolled before the study was closed as a result of a scheduled interim futility analysis. There were 13 ineligible patients; thus, 140 patients in each arm were assessable. In arm 1, 80% of patients completed all six cycles compared with 83% of patients in arm 2. Grade 4 granulocytopenia was more common in arm 1 (79% v 54%; P < .001) whereas grade 3 or worse anemia was more severe in arm 2 (6% v 18%; P < .003). The median progression-free survival was 1.03 years for arm 1 versus 1.05 years for arm 2. The median OS was 2.49 and 2.54 years for arms 1 and 2, respectively. There have been 237 reported deaths. The relative death rate was approximately 12% greater in arm 2 (hazard ratio, 1.12; 95% CI, 0.860 to 1.45). Conclusion Patients with advanced EOC have a relatively poor prognosis. The results of treatment with cisplatin and paclitaxel are not significantly improved by prolonging the paclitaxel infusion from 24 to 96 hours.

Does Severe Anemia Caused by Dose-Dense Paclitaxel-Carboplatin Combination Therapy Have an Effect on the Survival of Patients With Epithelial Ovarian Cancer? Retrospective Analysis of the Japanese Gynecologic Oncology Group 3016 Trial

2011 ◽  
Vol 21 (9) ◽  
pp. 1585-1591 ◽  
Author(s):  
Seisuke Kumagai ◽  
Toru Sugiyama ◽  
Tadahiro Shoji ◽  
Hirofumi Michimae ◽  
Noriyuki Katsumata ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Gynecologic Oncology Group ◽  
Severe Anemia ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Grade 3 ◽  
Dose Dense

IntroductionTo evaluate the incidence of anemia in patients with epithelial ovarian cancer receiving paclitaxel-carboplatin combination therapy (TC) using data from the Japanese Gynecologic Oncology Group (JGOG) 3016 trial, and to examine the effect of severe anemia on survival during dose-dense TC.MethodsRetrospective analysis was conducted in patients enrolled in the JGOG 3016 trial who underwent at least one cycle of the protocol therapy (n = 622). Hemoglobin values at enrollment and during each cycle of TC were collected. One-to-one matching was performed between patients with and patients without grade 3/4 anemia during TC (anemia and nonanemia groups) to adjust the baseline characteristics of the patients. The cumulative survival curve and median progression-free survival were estimated using the Kaplan-Meier method.ResultsGrades 2 to 4 anemia was observed in 19.8% of patients before first-line TC. The incidence of grade 3/4 anemia rapidly increased to 56.1% after the fourth cycle of dose-dense TC. After matching, the median progression-free survival in the anemia (hemoglobin <8.0 g/dL) and nonanemia (hemoglobin >8.0 g/dL) groups was 777 and 1100 days, respectively (P = 0.3493) for patients receiving dose-dense TC. The median progression-free survival in patients receiving conventional TC was similar between the 2 groups.ConclusionsThe difference in progression-free survival between patients with epithelial ovarian cancer with and those without severe anemia during TC was not statistically significant, but for patients receiving dose-dense TC, severe anemia seems to have prognostic relevance. Prospective trials are needed to investigate whether the optimal management of chemotherapy-induced anemia, including appropriate use of erythropoiesis-stimulating agents, would further improve the survival of patients with ovarian cancer receiving dose-dense TC.

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