8004 ORAL Safety and Efficacy Outcomes in Heavily and Non-heavily Pretreated Patients With Recurrent Ovarian Cancer (ROC) After Single-agent Trabectedin Treatment – Pooled Analysis of Phase II Trials

Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front-line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer.

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Phase II study on the combination carboplatin-celecoxib in heavily pre-treated recurrent ovarian carcinoma patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.15009 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 15009-15009

Author(s):

F. Legge ◽

V. Salutari ◽

A. Paglia ◽

A. Testa ◽

D. Lorusso ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Phase Ii ◽

Phase Ii Study ◽

Recurrent Ovarian Cancer ◽

Platinum Resistant ◽

Response To Chemotherapy ◽

Short Period ◽

Heavily Pretreated ◽

Cox 2

15009 Background: Cyclooxygenase-2 (COX-2) has been shown to be involved in several steps of ovarian onset and progression and its overepression is associated with a poor chance of response to chemotherapy and poor prognosis in ovarian cancer. Celecoxib, an orally active selective COX-2 inhibitor, has been tested for its ability to potentiate the activity of carboplatin in treatment of heavily pretreated recurrent ovarian cancer patients. Methods: A phase II study was planned, considering the regimen active if at least 12 responses were observed among the 43 enrolled patients. Celecoxib (400 mg/die), and carboplatin (5 AUC) q28 were administered, until progression or unacceptable toxicity. Response was assessed by RECIST and also by Rustin criteria. Results: 34 pts (median age: 60 yrs, range 28–74) and an ECOG performance status (0/1/2) of (21/12/1), were enrolled. 58.8% of patients were platinum resistant (progressing during or < 6 months from primary treatment). Median number of previous chemotherapy regimens was 3 (range 2–6). Currently 27 patients are evaluable for response. The overall response rate (CR and PR) was 25.9% (2 CR, 5 PR) with stabilization of disease in 8 patients (29.6%). Four responses occurred in platinum sensitive and 3 in platinum resistant group Median time to response was 11 weeks (range 9–19) and median duration of response was 23 weeks (range 12–39). According to Rustin criteria 10 patients out of 25 (40%) were considered responsive to treatment (return of CA125 levels to normal level or >50% reduction). Overall, 143 cycles were administered with a median value of 3 cycles (range = 1–10). Moderate/severe toxicities were as follows: G3 anemia occurred in 2.3% cycles, G3 neutropenia in 4.6% cycles, G3 thrombocytopenia in 1.5% cycles, G3/4 gastrointestinal toxicity occurred in 4.6% cycles. Cutaneous diffuse erithema was observed in 2 patients, in both cases recovered with a short period of antihistaminic treatment; 2 cases of hypertension were documented, G2 hypersensitivity reactions during carboplatin infusion were observed in 4 cases. Conclusions: Celecoxib combined with carboplatin is well tolerated and has promising activity as salvage treatment in heavily pretreated recurrent ovarian cancer patients. No significant financial relationships to disclose.

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Faculty Opinions recommendation of Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727010269.793552769 ◽

2018 ◽

Author(s):

Noelle LoConte ◽

Kieran Sahasrabudhe

Keyword(s):

Ovarian Cancer ◽

Elderly Patients ◽

Subgroup Analysis ◽

Single Agent ◽

Recurrent Ovarian Cancer ◽

Phase Iii ◽

Safety And Efficacy ◽

Platinum Resistant

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

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5579 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5579-5579 ◽

Cited By ~ 8

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.

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Effects of weekly bevacizumab and pegylated liposomal doxorubicin in heavily pretreated patients with recurrent or progressed ovarian cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5547 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5547-5547

Author(s):

Y. Kikuchi ◽

H. Kouta ◽

R. Kikuchi ◽

M. Takano ◽

T. Kita ◽

...

Keyword(s):

Ovarian Cancer ◽

Liposomal Doxorubicin ◽

Treatment Options ◽

Evaluation Criteria ◽

Pegylated Liposomal Doxorubicin ◽

Recurrent Ovarian Cancer ◽

Cytotoxic Agents ◽

Ca 125 ◽

Heavily Pretreated ◽

Pretreated Patients

5547 Background: Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded a promising therapeutic target. Bevacizumab (A) has significant antitumor activity in combination with cytotoxic agents. Currently, pegylated liposomal doxorubicin (D) is provided as one of the standard treatment options in recurrent ovarian cancer. Thus, we attempted to determine effects in combination of A and D for heavily pretreated patients with recurrent or progressed ovarian cancer. Methods: Twenty-two patients with heavily pretreated (more than one regimen or more than 6 cycles by paclitaxerl and carboplatin) received at least more than 3 cycles of weekly A-D consisting of A: 2 mg/kg and D: 10 mg/m2 (3 weeks, one week rest). The primary endpoint was response according to CA 125 and response evaluation criteria in solid tumor (RECIST) criteria. Results: Of 22 patients evaluable for CA 125 response, 7 (32%) had a response (decrease of >50%), and 8 (36%) patients had not progressed (doubling of CA 125) following 6 months on treatment. In RECIST evaluation, 2 (9%) patients had complete remission (CR) and 6 (27%) had partial remission (PR), resulting in 55% clinical benefit rate (CBR). Progression free interval (PFI) showed more than 6 months. Any hematological adverse effect was not observed in the present study. Gastrointestinal perforation was observed in only one case and was conservatively treated. Although nasal bleeding was frequently observed, no treatment was required. A induced hypertension was also observed and manageable. Hand-foot syndrome seemed due to D was seen in 3 of 22 patients and treatment was required in only one case. Conclusions: B seemed to enhance effect of D. This is the first study of weekly A-D in heavily pretreated ovarian cancer patients. Weekly A-D warrants further clinical study in such clinical settings. No significant financial relationships to disclose.

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