A phase II trial of voreloxin in women with platinum-resistant ovarian cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5559-5559
Author(s):  
H. W. Hirte ◽  
W. McGuire ◽  
R. Edwards ◽  
A. Husain ◽  
P. Hoskins ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Topoisomerase Ii ◽  
Single Agent ◽  
Safety Data ◽  
Dose Intensity ◽  
Clinical Activity ◽  
Platinum Resistant ◽  
Dose Levels ◽  
Dose Reductions

5559 Background: Voreloxin is a naphthyridine analog that intercalates DNA and inhibits topoisomerase II, inducing apoptosis. Clinical activity has been observed in ovarian cancer and AML. Results are reported from a fully enrolled phase II study of 3 dose levels of single agent voreloxin in patients (pts) with 1° or 2° platinum-resistant or refractory ovarian cancer. Methods: Pts may have received ≤ 3 prior platinum regimens plus one additional non-platinum regimen. PS of 0–1 was required. Voreloxin regimens: Cohort A 48 mg/m2q3weeks (wk) (N = 65), Cohort B 60 mg/m2q4wk (N = 35), and Cohort C 75 mg/m2q4wk (N = 35) by short IV infusion. BRCA status is reported by pt consent. Results: Cohort A: 2CRs, 5PRs; ORR 11%; median PFS 82 days (52–98 days 95%CI); Cohort B: 1CR, 3PRs; ORR 11%, median PFS too early to evaluate (TETE); Cohort C - TETE. Cohort A: Febrile neutropenia (FN) incidence was low (8%). Other common G3 or G4 AEs reported (≥ 5%) were fatigue (14%) and nausea (5%). Dose delays or reductions (40%) occurred typically at Cycle 1, largely due to neutropenia. Cohort B: Dose was increased to 60 mg/m2 and dosing interval was lengthened to 4 wk, maintaining dose intensity (DI) and allowing adequate time for marrow recovery. ANC dosing criterion was changed from ANC ≥ 1,500 to ≥ 1,000. There was a marked decrease in dose delays and reductions (14%) with only 3% incidence of FN. Common G3 or 4 AEs reported (≥ 5%) were fatigue (11%) and nausea (5%). The safety profile supported further dose escalation to 75 mg/m2q4wk (Cohort C- DI increased by 25%). Data are TETE. Conclusions: Preliminary data suggest Cohorts A and B have similar safety and efficacy profiles as anticipated based on comparable DI. Fewer dose reductions and delays occurred in Cohort B, due to revised dosing criteria and increased cycle length to 4 wk. Accrual to Cohort C is complete. Efficacy and safety data for all cohorts will be reported. [Table: see text]

Lenalidomide, Bortezomib, and Dexamethasone (Rev/Vel/Dex) as Front-Line Therapy for Patients with Multiple Myeloma (MM): Preliminary Results of a Phase 1/2 Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 187-187 ◽  
Author(s):  
Paul Richardson ◽  
Sundar Jagannath ◽  
Noopur Raje ◽  
Andrzej Jakubowiak ◽  
Sagar Lonial ◽  
...  
Keyword(s):  
Dose Level ◽  
Phase 1 ◽  
Single Agent ◽  
Safety Data ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Front Line ◽  
Dose Levels ◽  
Dose Reductions

Abstract Background: Bortezomib (VELCADE®, Vel) as a single agent and lenalidomide (Revlimid®, Rev) plus dexamethasone (Dex) are approved for the treatment of relapsed MM patients (pts) following ≥1 prior therapy. Rev/Vel±Dex is active and well tolerated in relapsed/refractory MM, and Rev/Dex and Vel/Dex have substantial activity in front-line MM. The aims of this phase 1/2 study were to determine the MTD of Rev/Vel/Dex in newly diagnosed MM pts, and to assess safety and efficacy. Methods: Pts received Rev 15–25 mg on d 1–14, Vel 1.0–1.3 mg/m2 on d 1, 4, 8, 11, and Dex 40/20 mg (cycles 1–4/5–8) on d 1, 2, 4, 5, 8, 9, 11, 12, for up to 8 21-d cycles, initially at 4 planned dose levels (Rev/Vel: 15/1.0, 15/1.3, 20/1.3, 25/1.3). Dose escalation proceeded (3-pt cohorts) depending on DLTs (G≥3 non-hematologic toxicity; G4 thrombocytopenia with platelets <10,000/mm3 on >1 occasion despite transfusion support; G4 neutropenia for >5 d and/or resulting in neutropenic fever; inability to receive cycle 2/d 1 dose due to drug-related toxicity). Based on safety data, dose level 4M was added with a reduced Dex starting dose (Rev/Vel 25/1.3, Dex 20 mg in all cycles). Toxicities were graded by NCI CTCAE v3.0. Pts with G>2 peripheral neuropathy (PNY) were excluded. Responses were assessed by modified EBMT and Uniform criteria. Pts with CR/nCR/VGPR/PR could proceed to ASCT after ≥4 cycles. Results: 33 pts (median age 56 yrs, 55% men, 84% IgG MM, 47% with ISS Stage II/III) have been enrolled to date in dose levels 1–4 and 4M, respectively, including 10 pts enrolled at the maximum planned dose (Dose Level 4M). Pts have received a median of 5 cycles; 9 pts have completed all 8 cycles. Two DLTs of G3 hyperglycemia due to high dose Dex were seen in dose level 4. Dose reductions in cycle 2 and beyond have occurred in dose levels 1–4 for Rev in 9 pts, Vel in 7 pts, and Dex in 17 pts, with 3 dose reductions having occurred in dose level 4M. Toxicities to date have been manageable. Only 1 G4 toxicity (thrombocytopenia) has been reported, plus 1 G3 DVT (reversed with LMWH), and no G≥3 PNY has been seen. The response rate across all dose cohorts (CR/nCR+VGPR+PR: subject to confirmation) is currently 89% in 25/28 evaluable pts, including 35% CR/nCR/VGPR. After median follow-up of 3 mos, median DOR, TTP, PFS, and OS have not been reached; all responders except 1 remain in remission, with 2 pts proceeding to ASCT. Conclusions: Rev/Vel/Dex is very active and well tolerated in newly diagnosed MM pts. The maximum planned dose has been reached at Rev 25 mg, Vel 1.3 mg/m2, and Dex 20 mg, with Phase 1 enrollment now complete using the lower dose of Dex. Enrollment to the Phase 2 component is ongoing.

Nonpegylated liposome-encapsulated doxorubicin (NPLED) and cyclophosphamide in the treatment of platinum-resistant ovarian cancer: Final results of a phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15544-e15544
Author(s):  
Daniela Sambataro ◽  
Melania Caruso ◽  
Concetta Di Blasi ◽  
Giuseppe Lavenia ◽  
Salvatore Asero ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Open Label Study ◽  
Free Survival ◽  
Resistant Refractory ◽  
Platinum Resistant

e15544 Background: Platinum resistant-refractory ovarian cancer (PRROC) patients have a poor outcome; single-agent therapy is still the gold standard, with overall response rate lesser than 20% and progression-free-survival is not higher than 4 months. Methods: We tested safety and activity of a two-drugs-regimen containing NPLED and cyclophosphamide in a phase II open label study. From October 2007 to October 2011 thirty-two patients with platinum-resistant/refractory disease were enrolled. Enrolled patients were pretreated with a median number of 2 lines of chemotherapy, ranging from 1 to 5. NPLED and cyclophosphamide were administered at the dose of 60 mg. and 600 mg p.s.m. respectively. Results: Patients received a median number of three cycles of chemotherapy. A total of 145 cycles were administered: as G3 toxicities we registered emesis (6%), diaorrhea (3%), asthenia, and alopecia. No grade 4 adverse events occurred. Among the 30 patients evaluable for response we observed 5 (17%) partial responses and 10 (33%) stable diseases. The median progression-free-survival was 13 weeks and the median survival was 46 weeks. Conclusions: These results are similar to other data reported in literature. In conclusion we may affirm that the association of NPLED and cyclophosphamide is active and safe when administered in PRROC, but it don’t modify the prognosis of this subset of patients.

A clinical study of tremelimumab alone or in combination with olaparib in patients with advanced epithelial ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6045-6045
Author(s):  
Stephanie Gaillard ◽  
Maureen Berg ◽  
Jeanne Harrison ◽  
Peng Huang ◽  
James M. Leatherman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Epithelial Ovarian Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Optimal Dose ◽  
Clinical Activity ◽  
Immune Mediated ◽  
Advanced Epithelial Ovarian Cancer ◽  
Dose Levels

6045 Background: Single agent immunotherapy (IO) has shown only modest clinical activity for the treatment of ovarian cancer. The combination of anti-programmed death-1 and PARP inhibitors showed promising activity in early trials. Here, we report the results of an open-label, parallel arm, dose escalation study of tremelimumab (T) alone or in combination with olaparib (O) in patients (pts) with advanced epithelial ovarian cancer (EOC). Methods: Pts with recurrent/persistent EOC who had progression < 12 months from last platinum exposure were enrolled. Prior therapy with IO (except anti-CTLA-4) or PARP inhibitor was allowed. Pts were randomized to either T 10mg/kg every 4 weeks (wks) x 7 then every 12 wks (Arm A) or T with O twice daily at three planned dose levels (Arm B). The primary objectives were safety, pharmacodynamic (PD) change in CD4+ICOShi peripheral T cells by flow cytometry, and identification of the optimal dose combination of T with O. Secondary objectives included 6-month progression-free survival (PFS6) and objective response rate (ORR). Results: A total of 24 pts were treated, 12 on Arm A, and 12 on two Arm B dose levels. Pts had a median age of 60 years (range 44-81). Histologic subtypes included high-grade serous EOC (20 pts, 83%), clear cell (3 pts, 13%), and moderately-differentiated adenocarcinoma (1 pt, 4%). BRCA1 mutation (mt) was present in 2 cases, BRCA2 mt in 1. Median number of prior regimens was 3.5 (range 1-9). Most adverse events (AEs) were attributable to T, the most common grade 3 toxicities were rash (13%), immune-mediated hepatitis (8%), and colitis (8%). No grade ≥4 toxicities were identified. Immune-mediated AEs also included acute kidney injury, hypophysitis, and hypothyroidism. No dose limiting toxicities were identified on Arm B. Two pts in Arm B had >PFS6. Of 20 pts evaluable for response, there was 1 partial response (Arm B), and 9 pts had stable disease (6 on Arm A, 3 on Arm B). Mean percentage of CD4+ICOShi T cells was significantly increased on Days 15 and 22 compared to Day 1 at both T dose levels (Table).T at 3 mg/kg with O at 150mg is the optimal dose of those tested. Conclusions: T and T with O was tolerable, with modest clinical activity in this pt population. AEs were as expected, and peripheral CD4+ICOShi T cells increased on therapy. Clinical trial information: 02485990. [Table: see text]

Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma.

1996 ◽  
Vol 14 (5) ◽  
pp. 1552-1557 ◽  
Author(s):  
A P Kudelka ◽  
D Tresukosol ◽  
C L Edwards ◽  
R S Freedman ◽  
C Levenback ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Optimal Dose ◽  
Dose Schedule ◽  
Clinical Activity ◽  
Major Toxicity ◽  
Gastrointestinal Side Effects ◽  
Eligibility Requirements ◽  
Dose Reductions

PURPOSE To determine the efficacy and toxicity of topotecan administered as a 5-day intravenous infusion in patients with advanced ovarian cancer refractory to cisplatin-based chemotherapy. PATIENTS AND METHODS Thirty patients with advanced epithelial ovarian cancer refractory to cisplatin-based chemotherapy received intravenous infusions of topotecan 1.5 mg/m2 delivered over 30 minutes each day for 5 days. A course was repeated every 21 days. The patient eligibility requirements included age > or = 18 years, Zubrod score < or = 2, measurable disease, adequate hepatic and renal function, neutrophil count > or = 1,500/microL, platelet count > or = 100,000/microL, and anticipated survival > or = 3 months. RESULTS Twenty eight patients were assessable for response and toxicity. All patients were assessable for survival. The major toxicity from administration of topotecan at this dose schedule was myelosuppression; 21 patients required dose reductions. Four patients had neutropenic fever that required hospitalization, and seven patients required platelet transfusions. Maculopapular pruritic exanthema occurred in 20% of patients; gastrointestinal side effects were mild. No deaths were reported on the study. At dose levels of 1.5, 1.25, and 1.0 mg/m2, 61%, 31%, and 25% of patients, respectively, required dose reductions. Of 28 assessable patients, four (14%; 95% confidence interval [CI], 4% to 34%) achieved a partial response (PR) at a median of 1.4 months and lasting 8.9 months, and 17 had stable disease (SD). The overall median survival time was 10.0 months (95% CI, 8.1 to 13.5). CONCLUSION Topotecan shows modest clinical activity against cisplatin-refractory ovarian cancer, although the dose-intensity is compromised by the depth of the granulocyte nadir and the duration of granulocytopenia. Further studies of topotecan may necessitate a reevaluation of optimal dose schedule, with the possible incorporation of multilineage cytokines, and its activity in taxane-resistant tumors.

Capecitabine plus docetaxel (XT): A first line, phase II clinical trial in metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10624-10624
Author(s):  
C. L. Vogel ◽  
E. Tan-Chiu ◽  
F. Gokce
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
Toxicity Profile ◽  
Nail Changes ◽  
The Mean ◽  
Dose Levels ◽  
Higher Doses ◽  
Dose Reductions

10624 Background: The XT combination originally published at (X) dosed at 1250 mg/m2 bid po x 14 days and (T) at 75 mg/m2 q3 weeks I.V. respectively yielded good response rates and an overall survival advantage compared with single agent docetaxel at 100 mg/m2. However, the toxicity profile of this regimen has led to major dose and schedule modifications by most oncologists. Methods/Results: We initiated a Phase II trial at doses of X at 900 mg/m2 bid po x 14 days and T at 36 mg/m2 d 1 and 8. Three responded and the mean no. of cycles for these patients was 3.8. Since four of 6 went off study because of toxicity two additional dose levels were studied in 6 patients each. A second cohort received X at 650 mg/m2 bid and T at 30 mg/m2. With 6 evaluable patients, four of 6 responded but all 4 required further dose reductions. Mean no. of cycles received was 4.2. A third cohort of 6 patients received X at 825 mg/m2 plus the lower T at 30mg/m2 who received a mean no. of cycles of 6. While only 1/6 responded 3 additional patients had stable disease with marked decreases in CEA or CA 15–3 suggestive of anti-tumor response. Only 1/6 required a dose reduction. Among the 18 patients, epiphora was described by 5 (28%). Only 3 patients developed significant leukopenia, and thrombocytopenia was not seen. T-induced nail changes were uncommon but were severe in one patient. Two patients at the first dose level, but only one at lower levels developed mucositis. Grade 1 anemia was common but managed easily with growth factor support. Conclusions: The response rate of 44% is encouraging with these lower doses of XT. We recommend further studies using X at 825 mg/m2 and T at 30mg/m2 since these doses were associated with encouraging response rate and a better toxicity profile than higher doses. Even at this higher dose of X dose reductions may well be needed. (Supported by a grant from Roche Laboratories, Inc.) No significant financial relationships to disclose.

Clinical activity of imatinib mesylate in combination with docetaxel in patients with advanced, platinum-resistant ovarian cancer—Hoosier Oncology Group GYN03–62

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5091-5091 ◽  
Author(s):  
D. Matei ◽  
R. E. Emerson ◽  
N. Menning ◽  
J. Schilder ◽  
J. McClean ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Response Rate ◽  
Advanced Ovarian Cancer ◽  
Ovarian Tumors ◽  
Phase Ii Clinical Trial ◽  
Ovarian Cancer Cells ◽  
Clinical Activity ◽  
Platinum Resistant

5091 Background: Ovarian tumors harborc-Kit and PDGF receptors. We showed in an in-vitro model that Imatinib (G) inhibits the growth of ovarian cancer cells. We hypothesized that G in combination with chemotherapy inhibits the growth of ovarian tumors. Data from a phase II clinical trial utilizing G in combination with Docetaxel (D) in patients with advanced ovarian cancer (OC) are presented. Methods: This was an open label, one stage, multi-center phase II clinical trial. Planned sample size was 23. Patients with relapsed, platinum-resistant or refractory OC expressing PDGFR or c-kit were eligible. PDGFR and c-kit expression was assessed prior to enrollment by IHC using archival tumor tissue. G was administered at 600mg/d continuously and D was given weekly (30mg/m2) for 4 weeks, with 2 weeks break. Each cycle was 6 weeks, with a maximum of 6 cycles allowed. Tumor assessments were obtained after 2, 4 and 6 cycles. Response rate by RECIST was the primary endpoint. Results: 34 patients were screened. 17 tumors were c-kit + and 25 were PDGFRα +. 23 patients were enrolled. Of those, 4 patients had c-kit+/PDGFR- tumors, 12 were PDGFR+/c-kit- and 7 were c-kit+/PDGFR+. Median age was 55 (range 33–76) and median PS was 0 (range 0–2). Median number of prior treatments was 3 (range 1–9). Efficacy and toxicity data are available for 20 and 14 patients, respectively. Based on RECIST, there were 3 patients with PR and 3 patients with SD lasting at least 12 weeks. Of these 6 patients, 2 pts were c-kit+, 2 were PDGFR+ and 2 were PDGFR and c-kit+. All 6 patients had carboplatin and taxane resistant disease. Grade 3–4 toxicities were: neutropenia (2), thrombocytopenia (1), fatigue (1), dehydration (1), constipation (1), cardiac ischemia (1), nausea/vomiting (2), urinary frequency (1). Other G1–2 toxicities were: N/V (9), diarrhea (7), fatigue (8), mucositis (4), anemia (4), hypocalcemia (5), rash (6), anorexia (7), edema (5), hemolysis (1), non-neutropenic infections (7). Additional data will be available in May 2006. Conclusions: The combination G+D is tolerated well. Clinical activity consisted of 3 PRs (15% response rate) and 3 SD > 3 months in pts with heavily pre-treated, platinum resistant OC expressing c-kit or PDGFRα. [Table: see text]

Trabectedin (T) in relapsed advanced ovarian cancer (ROC): A pooled analysis of three phase II studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5579-5579 ◽  
Author(s):  
S. McMeekin ◽  
J. M. del Campo ◽  
N. Colombo ◽  
C. Krasner ◽  
A. Roszak ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Clinical Activity ◽  
Weekly Schedule ◽  
Phase Ii Trials ◽  
Phase Ii Studies

5579 Introduction: Trabectedin is a DNA minor groove binding drug with a distinct MoA under development in sarcoma, prostate, breast and ROC. We have performed a pooled analysis of efficacy and tolerability of all phase II trials with T as 2nd - 3rd line in ROC. Methods: Three Trabectedin schedules were investigated: two every 3weeks (q3w; A: 1.3 mg/m2 3-h or B: 1.5 mg/m2 24-h) and one weekly (C: 0.58 mg/m2 3-h ×3 q4w). Endpoints were response rate (RR), time to progression (TTP), response duration (RD) and safety. 294 patients from 3 phase II (one randomized A vs B) trials were included: 108 were resistant (R) and 186 sensitive (S) to last platinum, based on progression-free interval <6 months or longer.Results: Overall RR and median TTP were 8% and 2.1mo in R and 34% and 5.8 mo in S patients. Median RD was 5.8 m. Schedules A & B q3w showed significant better RR (33% vs 16%, p=<0.0001) and median TTP (5.8 vs 2.8 m, p=0.0001) than the weekly schedule C. No efficacy difference was seen between 3-h and 24-h q3wk. In patients with = 2 prior platinum-based regimens, RR (R:7% and S:37%) and median TTP (R: 2.5 m and S:6.3 m) were similar than patients with only 1 prior platinum [RR (R:9%; S:33%) and TTP (R: 2 m; S: 5.5 m)]. 1,404 cycles were delivered [median A: 5(1–23), B: 5(1–19), C: 3(1–22)], with similar dose intensity (mg/m2/wk) across regimens (0.38, 0.42, 0.39). Most common drug-related AEs of any grade by cycle were (A, B, C) fatigue: 38, 35, 63% and vomiting: 16, 27, 21%. Grade 3/4 lab abnormalities were non-cumulative neutropenia: 21, 28, 1% and ALT increase: 32, 26, 3%. Low incidence of febrile neutropenia, neurotoxicity, stomatitis and alopecia was seen regardless of schedule. Conclusions: Trabectedin as single agent has shown clinical activity in both R and, particularly in S ROC. Activity was fully retained in patients with =2 prior platinum lines. Trabectedin q3w schedules (with no difference between 3 and 24-h) showed higher efficacy than T weekly. Toxicities were manageable and non-cumulative. Trabectedin is a promising new drug for the treatment of ROC and is under evaluation in a phase III trial. No significant financial relationships to disclose.

Lenalidomide, Bortezomib, and Dexamethasone (Rev/Vel/Dex) in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Preliminary Results of a Phase II Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2714-2714 ◽  
Author(s):  
Paul Richardson ◽  
Sundar Jagannath ◽  
Noopur Raje ◽  
Andrzej Jakubowiak ◽  
Sagar Lonial ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Phase 1 ◽  
Single Agent ◽  
Clinical Activity ◽  
Maintenance Schedule ◽  
Prior Therapy ◽  
Phase 2 Study ◽  
Cardiac Medication ◽  
Dose Levels ◽  
Dose Reductions

Abstract Background: Single-agent bortezomib (VELCADE®, Vel) and lenalidomide (Revlimid®, Rev) plus dexamethasone (Dex) are approved for relapsed MM patients (pts) following ≥1 prior therapy. Preclinical studies show Rev sensitizes MM cells to Vel and Dex, suggesting combination therapy may enhance clinical activity. In a phase 1 study, Rev/Vel (MTD 1.0mg/m2/15mg) ± Dex (20–40mg) was well tolerated and resulted in a response rate (CR+PR+MR) of 58% in relapsed and/or refractory MM pts. The aim of this multicenter phase 2 study was to evaluate the efficacy and safety of Rev/Vel/Dex (RVD) at the phase-1 MTD in up to 64 relapsed and/or refractory MM pts. Methods: Pts with relapsed/refractory MM and 1–3 prior lines of therapy received up to eight 21-d cycles of Vel 1.0mg/m2, d 1, 4, 8, 11, Rev 15mg, d 1–14 of a 21-d cycle, and Dex 40mg (cycles 1–4)/20mg (cycles 5–8), days of/after Vel dosing. After cycle 8, pts with stable or responding disease were allowed to continue on a maintenance schedule with Vel (d 1 and 8) and Rev (d 1–14) at the dose levels tolerated at the end of cycle 8, with Dex at 10mg (d 1, 2, 8, 9). Pts received concomitant antithrombotic and antiviral prophylaxis. Response was assessed according to modified EBMT and Uniform criteria with toxicities assessed using NCI CTCAE v3.0. Results: 27 pts (19 men, 8 women) have been enrolled to date, including 16 with relapsed and 11 with relapsed and refractory MM. Median age was 71 yrs (range 51–83) and median no. of prior therapies was 2 (range 1–3), including prior SCT in 7, prior Vel in 18, prior Rev in 1, prior thalidomide in 21 and prior Dex in 22 pts. Pts received a median of 7 cycles (range 1–15); 10 pts completed 8 cycles and 5 pts continued on maintenance. Dose reductions were required for Rev in 4, Vel in 4 and Dex in 11 pts. Toxicities were manageable and consisted primarily of G1-2 myelosuppression. Attributable non-hematologic toxicities included 1 DVT in the context of air travel in a pt who had been receiving aspirin 81mg as thromboprophylaxis. Enoxaparin and Coumadin were administered and the pt continued on therapy. Two episodes of atrial fibrillation (G3) were reported, reversed with cardiac medication, attributed to Rev/Dex, prompted Dex dose reduction and have not recurred. G3 PN was reported in only 1 pt despite Vel dose reduction, resulting in treatment discontinuation. In 24 evaluable pts, ORR (CR/nCR+VGPR+PR+MR) is currently 79%, including 33% CR/nCR/VGPR. Conclusions: RVD is very active in pts with relapsed and/or refractory MM, including pts with prior Rev, Vel, thalidomide, and SCT. Dex dose reduction was required in 11 pts and the protocol has been amended to use lower dose Dex at 20 mg, but the combination has been otherwise well tolerated, with low rates of DVT and PN. Accrual is ongoing.

Experience With Bevacizumab in the Management of Epithelial Ovarian Cancer

2007 ◽  
Vol 25 (20) ◽  
pp. 2902-2908 ◽  
Author(s):  
Robert A. Burger
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Single Agent ◽  
Safety Data ◽  
Phase Iii ◽  
Primary Therapy ◽  
Phase Ii Trials ◽  
Anti Vegf ◽  
Taxane Chemotherapy

Müllerian duct adenocarcinomas, in particular epithelial ovarian cancers, continue to represent a major source of female cancer-related morbidity and mortality, despite advances in surgical management and innovations in cytotoxic chemotherapy. Angiogenesis-targeted therapy seems to be appropriate for exploration in these disease processes based on a wealth of evidence from preclinical and molecular epidemiology studies. Bevacizumab is a prototypical agent neutralizing vascular endothelial growth factor (VEGF), a critical angiogenic promoter related to tumor progression, malignant effusions, and prognosis in ovarian cancer. Phase II trials have demonstrated the activity of bevacizumab as a single agent and in combination with other modalities such as low-dose metronomic cyclophosphamide. Historical studies have supported these observations. Unique toxicities have been ascribed to the administration of bevacizumab and other anti-VEGF molecules for patients with this disease and other solid tumors. Although most of these toxicities (such as proteinuria, hypertension, and bleeding) are generally mild, and are either self-limiting or controllable, other adverse effects, though uncommon, may be serious (these include arterial thromboembolism, wound healing complications, and GI perforation or fistulae). Phase III trials are now in progress to determine the role of this drug in primary therapy as an adjunct to platinum-taxane chemotherapy. This article reviews the background and rationale for anti-VEGF therapy of ovarian cancer, summarizes efficacy and safety data from phase II trials and historical studies of bevacizumab in this disease, introduces the implementation of bevacizumab in phase III front-line trials, examines controversial aspects related to anti-VEGF therapy, and proposes future directions regarding bevacizumab and other angiogenic growth factor–targeted therapeutics.

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