scholarly journals A Retrospective Analysis of Vinorelbine Chemotherapy for Patients With Previously Treated Soft-Tissue Sarcomas

Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-4 ◽  
Author(s):  
Sibyl E. Anderson ◽  
Mary L. Keohan ◽  
David R. D'Adamo ◽  
Robert G. Maki
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Epithelioid Sarcoma ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Median Number ◽  
Kaplan Meier ◽  
Pretreated Group ◽  
Heavily Pretreated ◽  
Grade 3

Introduction. The role of vinorelbine in specific soft tissue sarcoma subtypes is unclear. We present retrospective single institution experience with single-agent vinorelbine in subjects with metastatic soft tissue malignancies.Methods. Fifty-eight patients were treated with single agent intravenous vinorelbine between April 1997 and December 2004. Doxorubicin had been administered previously to 53 subjects (91%), and the median number of lines of previous chemotherapy was 3 (range 0–7).Results. Patients received a median 6 doses of vinorelbine (range 1–65). The overall response rate was 6%(3 patients: 1 angiosarcoma, 1 epithelioid sarcoma, and 1 embryonal rhabdomyosarcoma). Fourteen patients (26%) experienced a best result of stable disease. Median time to progression was 1.8 months (95%confidence intervals 1.5–2.1 months, Kaplan-Meier estimate). Eight patients experienced grade 3 or 4 toxicity, most commonly febrile neutropenia.Conclusion. Vinorelbine demonstrates limited activity in a heavily pretreated group of soft-tissue sarcoma patients. Prospective investigation may be considered for selected sarcoma subtypes.

scholarly journals A Phase II Study of Flavopiridol in Patients With Previously Untreated Advanced Soft Tissue Sarcoma

Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
Don G. Morris ◽  
Vivien H. C. Bramwell ◽  
Robert Turcotte ◽  
Alvaro T. Figueredo ◽  
Martin E. Blackstein ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Dose Intensity ◽  
Advanced Soft Tissue Sarcoma ◽  
Kaplan Meier ◽  
Treatment Responses ◽  
Grade 3

Purpose. Flavopiridol is a potent cyclin-dependent kinase (CDK) inhibitor that has preclinical activity in many tumours. This synthetic flavonoid was tested in a phase II nonrandomized, nonblinded multicentre clinical trial to determine its activity and toxicity in patients with previously untreated metastatic or locally advanced soft tissue sarcoma.Methods. A total of 18 patients with histologically confirmed nonoperable soft tissue was treated with flavopiridol administered at a dose of 50 mg/m2IV over 1 hour daily×3days every 3 weeks.Results. Eighteen patients were accrued to the study over a period of 6 months. No objective responses were noted in the seventeen evaluable patients. Eight patients (47%) exhibited stable disease after 2 cycles (median duration of 4.3 months (range 1.4–6.9 months). Kaplan-Meier estimates for 3- and 6-month progression-free survivial rates were 44 percent and 22 percent, respectively. The only grade 3 toxicities were diarrhea (N=2), nausea (N=2), gastritis (N=1), and fatigue (N=1). Ninety-four percent of patients received≥90% of the planned dose intensity, during 55 treatment cycles.Conclusions. Flavopiridol was well tolerated at the dose and schedule used in this study, however, no objective treatment responses were seen and thus our results do not support further exploration of flavopiridol as a monotherapy at this dose and schedule in soft tissue sarcomas.

Phase II Study of Doxorubicin and Bevacizumab for Patients With Metastatic Soft-Tissue Sarcomas

2005 ◽  
Vol 23 (28) ◽  
pp. 7135-7142 ◽  
Author(s):  
David R. D'Adamo ◽  
Sibyl E. Anderson ◽  
Karen Albritton ◽  
Jennifer Yamada ◽  
Elyn Riedel ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Stable Disease ◽  
Cardiac Toxicity ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Close Monitoring ◽  
Future Studies ◽  
Metastatic Soft Tissue Sarcoma ◽  
Grade 3 ◽  
Line Of Therapy

Purpose To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS). Patients and Methods Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2. Results A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related. Conclusion The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.

Efficacy and safety of amrubicin in patients with advanced or recurrent thymoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17513-e17513
Author(s):  
Kiyotaka Yoh ◽  
Koichi Goto ◽  
Seiji Niho ◽  
Shigeki Umemura ◽  
Hironobu Ohmatsu ◽  
...  
Keyword(s):  
Tumor Size ◽  
Single Agent ◽  
Reduction Rate ◽  
Progression Free Survival ◽  
Median Number ◽  
Significant Activity ◽  
Efficacy And Safety ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Number Of Treatment

e17513 Background: Thymoma is rare thoracic tumor, which is chemoresponsive with anthracycline or cisplatin-containing regimen in advanced or recurrent setting. Amrubicin is a novel anthracycline agent that is well known to exert significant activity against small-cell lung cancer. The purpose of this study was to determine the efficacy and safety of amrubicin in patients with advanced or recurrent thymoma. Methods: We reviewed 11 consecutive patients with advanced or recurrent thymoma treated with single-agent amrubicin therapy at our institution from May 2006 to September 2010, retrospectively. Amrubicin was administered intravenously at 40 or 45 mg/m2 on day 1 to 3 of 3-4 weeks until disease progression or development of intolerance. Results: Profile of patients included: median age was 57 years (range 25–74); Male/Female=5/6; PS 0/1= 7/4; and Masaoka stage IVA/IVB/recurrence=7/2/2. All patients had received no prior chemotherapy. The median number of treatment cycles was 4 (range 3-6). A partial response was achieved in 1 patient and 10 patients exhibited stable disease. The overall response rate was 9%, but 3 patients had at least a 20% reduction in tumor size with amrubicin. The median reduction rate in tumor size was 13% (range 0-40). The median progression-free survival period was 5.4 months (range 2.3-15.8 months). The median overall survival has not been reached although a median follow-up time was 2.5 years. Based on the Kaplan-Meier method, the estimated 3-year survival rate was 83%. The most common adverse events were hematological toxicities. Five patients had grade 3/4 neutropenia, but febrile neutropenia was not observed. Non-hematological grade 3 toxicities were less frequent. There were no treatment-related deaths. Conclusions: Single-agent amrubicin showed modest activity and acceptable safety profile as chemotherapy for advanced or recurrent thymoma. Additional testing of amrubicin combined with cisplatin in this disease is warranted.

scholarly journals Soft Tissue Sarcoma Guidelines

2007 ◽  
Vol 5 (4) ◽  
pp. 364 ◽  
Author(s):  
_ _
Keyword(s):  
United States ◽  
Soft Tissue ◽  
Mortality Rate ◽  
Soft Tissue Sarcoma ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
The United States ◽  
Desmoid Tumors ◽  
Recent Version ◽  
Overall Mortality

Soft tissue sarcomas are the most frequent sarcomas; the annual incidence for 2007 in the United States is estimated at about 9220 cases, with an overall mortality rate of approximately 3560 cases per year. Important updates for the 2007 version of the guidelines include the addition of epirubicin (single agent) and the combination of epirubicin, ifosfamide, and mesna as generally accepted systemic therapy. Imatinib was added as an option for desmoid tumors. For the most recent version of the guidelines, please visit NCCN.org

Histologic Grade Predicts Recurrence for Marginally Excised Canine Subcutaneous Soft Tissue Sarcomas

2009 ◽  
Vol 46 (5) ◽  
pp. 928-933 ◽  
Author(s):  
K. D. McSporran
Keyword(s):  
Soft Tissue ◽  
Local Recurrence ◽  
Tumor Recurrence ◽  
Soft Tissue Sarcomas ◽  
Rank Test ◽  
Survival Curves ◽  
Marginal Excision ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Grade 3

Local recurrence of marginally excised subcutaneous soft tissue sarcomas is variable and difficult to predict. This study aimed to identify predictors of local recurrence after excisional biopsy. Medical records of 236 dogs from which tumors had been received between 2004 and 2007 were analyzed. Medium- to large-breed dogs, median age 10 years, were most commonly affected. A total of 139 tumors were graded histologically: 71 were grade 1 (51%); 59, grade 2 (42%); and 9, grade 3 (7%). Of these, 34 tumors (25%) were completely excised, and 104 (75%) were marginally excised. None of 30 completely excised tumors with follow-up information recurred. Three of 41 grade 1 tumors (7%), 14 of 41 grade 2 tumors (34%), and 3 out of 4 grade 3 tumors recurred after marginal excision. Kaplan-Meier survival curves were generated to evaluate survival and the tumor-free interval. The log-rank test and log-rank test for trend were used for comparisons. Tumor recurrence-free intervals for dogs with grade 1 and 2 tumors and for those with grade 1 and 3 tumors differed significantly ( P = .0027 and .0001, respectively) and overall were inversely related to tumor grade ( P = .0007). Kaplan-Meier survival curves, regardless of recurrence, for patients with grade 1, 2, or 3 tumors treated by marginal excision did not differ significantly, and none differed from the survival curves of patients treated by complete excision. In conclusion, histologic grade is a strong predictor for recurrence of marginally excised subcutaneous soft tissue sarcomas. Clean margins predict nonrecurrence. Tumor recurrence did not significantly reduce survival time.

scholarly journals Phase 2A Study of Copanlisib, a Novel PI3K Inhibitor, in Patients with Indolent Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1701-1701 ◽  
Author(s):  
Martin Dreyling ◽  
David Cunningham ◽  
Krimo Bouabdallah ◽  
Sarit Assouline ◽  
Eric Van den Neste ◽  
...  
Keyword(s):  
Exploratory Study ◽  
Research Funding ◽  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Pi3k Inhibitor ◽  
Aggressive Lymphoma ◽  
Heavily Pretreated ◽  
Grade 3

Abstract Background: Copanlisib is a novel pan-Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with potent preclinical inhibitory activity against both PI3K-d and PI3K-α isoforms. Preliminary results from a phase II study of copanlisib in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) have been reported (Dreyling et al., ASH 2013), with an expansion cohort for patients with aggressive lymphoma still ongoing. We report here the final results of this exploratory study for patients with indolent NHL or CLL treated with copanlisib. Methods: Patients with histologically confirmed indolent NHL or CLL and relapsed or refractory to ≥2 prior lines of treatment were eligible. Copanlisib was administered at a dose of 0.8 mg/kg as a 1 hour intravenous infusion on days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as assessed per independent radiologic review according to the response criteria for lymphoma (Cheson et al., JCO 17:1244,1999) or the guidelines for diagnosis and treatment of CLL (Hallek et al., Blood 111:5446-56, 2008). Secondary endpoints included progression-free survival (PFS) and duration of response (DOR), safety and tolerability. Results: A total of 33 patients were treated in the indolent group, including: follicular NHL (FL) = 16, CLL = 13, marginal zone lymphoma (MZL) = 3, and small lymphocytic lymphoma (SLL) = 1. Median age was 68 years (range 46-89), M/F= 15/18. The median number of previous lines of treatment was 4. Thirty patients (91%) were previously exposed to rituximab. The median number of cycles received was 5.7 (mean 7.2); the median dose and median cumulative dosage of copanlisib administered were 52 mg (87% of planned dose) and 687 mg, respectively. Five patients were dose reduced to 0.6 mg/kg and 1 to 0.4 mg/kg. The ORR as determined by independent radiologic review in 32 evaluable patients was 47%, with 1 CR, 1 uCR, and 13 PRs. By histology, there were 1 CR, 1 uCR and 5 PRs for patients with FL (ORR 47%), and 2/3 PRs for patients with MZL and 1/1 PR for the patient with SLL, for an overall ORR for patients with indolent NHL (excluding CLL) of 53%. The ORR for patients with CLL was 38% (all PRs). Overall, the median DOR was 287 days (95% CI: 56; not yet reached); median PFS was 240 days (95% CI: 173; 419). The most common adverse events (AEs) of all grades were hyperglycemia (70%), hypertension (70%), fatigue (64%), diarrhea (36%), neutropenia (36%) and anemia (33%). Grade 3-4 AEs occurring in >10% of patients included: hypertension (49% grade 3), neutropenia (30%), hyperglycemia (30% grade 3), and anemia (15%). Dose reductions, interruptions, or permanent discontinuations due to AEs were reported in 4 (12%), 21 64%), and 11 (33%) patients, respectively. There was one drug-related grade-5 event; meningitis in a heavily-pretreated CLL patient with longstanding disease-related immunodeficiency, occurring shortly after first administration of copanlisib. Conclusions: Copanlisib is active as a single-agent in heavily pretreated, advanced refractory/relapsed FL, MZL, SLL, and CLL. Copanlisib exhibited an acceptable toxicity profile, consistent with previous reports. Based on the results of this exploratory study, a phase 2B study of copanlisib in relapsed or refractory indolent NHL (after prior treatment with an alkylating agent and rituximab) has been initiated and is ongoing. Disclosures Dreyling: Bayer HealthCare: Scientific advisory board/consultant Other. Cunningham:Roche: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Merck Serono: Research Funding; Novartis: Research Funding; Astra Zeneca: Research Funding. Giurescu:Bayer Pharma AG: Employment. Mappa:Bayer S.p.A.: Employment. Grunert:Bayer Pharma AG: Employment. Childs:Bayer HealthCare Pharmaceuticals: Employment.

Phase II Trial of Irinotecan in Children With Relapsed or Refractory Rhabdomyosarcoma: A Joint Study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group

2007 ◽  
Vol 25 (4) ◽  
pp. 356-361 ◽  
Author(s):  
Gilles Vassal ◽  
Dominique Couanet ◽  
Elizabeth Stockdale ◽  
Anne Geoffray ◽  
Birgit Geoerger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Tumor Burden ◽  
French Society ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Multiagent Chemotherapy

PurposeThis phase II study was designed to evaluate the efficacy of irinotecan administered intravenously once every 3 weeks in pediatric patients with recurrent or refractory rhabdomyosarcoma.Patients and MethodsA total of 35 patients younger than age 20 years, with refractory or relapsed rhabdomyosarcoma for which standard treatments have failed, received irinotecan at 600 mg/m2administered as a 60-minute infusion every 3 weeks. Concomitant treatments included atropine for cholinergic symptoms, loperamide for diarrhea at the first liquid stool, and preventive antiemetic treatment. Tumor response was assessed every two cycles until progression according to WHO criteria.ResultsThe best overall response rate to irinotecan was 11.4% (95% CI, 3.2 to 26.7%; 2.9% complete responses, 8.5% partial responses) from all patients recruited. The median times to progression and survival were 1.4 and 5.8 months, respectively. A total of 112 cycles were administered, with a median number of two cycles per patient (range, 1 to 16). The most common grade 3/4 toxicities were neutropenia (46%), abdominal pain or cramping (17%), cholinergic syndrome (14%), nausea/vomiting (11%), anemia (11%), thrombocytopenia (9%), and diarrhea (6%).ConclusionIn heavily pretreated children with a high tumor burden who have been treated with multiagent chemotherapy, irinotecan administered intravenously as a single agent, at 600 mg/m2every 3 weeks, showed an interesting objective response rate and a good tolerance profile in rhabdomyosarcoma.

Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas.

1993 ◽  
Vol 11 (7) ◽  
pp. 1269-1275 ◽  
Author(s):  
J H Edmonson ◽  
L M Ryan ◽  
R H Blum ◽  
J S Brooks ◽  
M Shiraki ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Tumor Regression ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Phase Iii ◽  
Significant Survival ◽  
Receive Treatment ◽  
Grade 3 ◽  
Group B ◽  
Survival Differences

PURPOSE This three-armed phase III study in adults with advanced soft tissue sarcomas was planned as a comparison of objective regression rates, toxicity, and survival of patients receiving doxorubicin alone, ifosfamide plus doxorubicin, and mitomycin plus doxorubicin plus cisplatin. PATIENTS AND METHODS Between December 1987 and July 1990, 279 patients with histologically confirmed sarcomas were enrolled to receive treatment A (doxorubicin 80 mg/m2), treatment B (ifosfamide 7.5 g/m2 plus doxorubicin 60 mg/m2), or treatment C (mitomycin 8 mg/m2 plus doxorubicin 40 mg/m2 plus cisplatin 60 mg/m2). RESULTS Of 262 assessable patients, 74 (29%) achieved objective tumor regression. Objective regression occurred in 20% of the 90 patients who received doxorubicin alone (complete remission [CR] rate, 2%), in 34% of the 88 who received ifosfamide plus doxorubicin (CR rate, 3%), and in 32% of the 84 who received mitomycin plus doxorubicin plus cisplatin (CR rate, 7%). With grade 3 or greater myelosuppression in 53% of group A, 80% of group B, and 55% of group C, regimen B was significantly more myelosuppressive than either regimen A or C (P = .01) with two, three, and one treatment-related deaths, respectively. Synovial sarcomas were responsive to ifosfamide plus doxorubicin, especially among patients younger than 40 years of age. CONCLUSION Ifosfamide plus doxorubicin produced a significantly higher regression rate (P = .03) than did doxorubicin alone; however, this was achieved at a level of myelosuppression significantly more intense than that produced by the single agent or by the three-drug combination. Mitomycin, doxorubicin, and cisplatin also appeared to be more active than the single agent; however, at a myelosuppression level similar to that of doxorubicin alone, this trend (P = .07) did not attain the usual level for significance. No significant survival differences were observed.

Phase II Study of Dasatinib in Patients with Relapsed CLL

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4197-4197 ◽  
Author(s):  
Ravin Jain Garg ◽  
William Wierda ◽  
Luis Fayad ◽  
Zeev Estrov ◽  
Susan M Bickel ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Median Number ◽  
The Other ◽  
Biologic Activity ◽  
Pretreated Group ◽  
Heavily Pretreated ◽  
B Cell Leukemia ◽  
Grade 3 ◽  
Persistent Headache

Abstract Preclinical studies have demonstrated that the Src-related tyrosine kinase Lyn is upregulated and constitutively activated in CLL cells. Lyn inhibitors have been shown to reduce survival of CLL cells in vitro and the Src inhibitor PPW results in the death of murine B cell leukemia. This has spurred interest in the role of Src inhibition as a treatment option for patients with CLL. Dasatinib is a dual Src- and Abl-kinase inhibitor that was recently approved by the FDA for the treatment of patients with CML failing imatinib. It has been shown to induce apoptosis in CLL cells in vitro. The aim of this study was to investigate the activity of dasatinib in patients with relapsed CLL. Patients with relapsed CLL, SLL, T-PLL and normal organ function were eligible. The dose of dasatinib was 50 mg PO bid continuously with possible escalation up to 70 mg bid. Each cycle was 4 weeks. Thirteen patients have been treated. The median age was 67 years (range, 42 to 83). The median number of prior treatments was 4 (range, 1 to 8). Five patients (38%) had Rai stage 0–1 disease, the other 8 (62%) had stage II–IV disease. Two patients were inevaluable for response; one changed his mind after only 2 days of treatment and the other patient was hospitalized with Aspergillus 2 weeks into treatment. Of the remaining 11 patients, 6 were treated for 3 cycles, 1 for 6 cycles, 1 is still on treatment, and 3 had therapy stopped after 2, 15, and 34 days for lip numbness, persistent headache, and thrombocytopenia/fatigue, respectively. Five patients had dose escalation after cycle 1, and 1 patient had escalation after cycle 3. The Grade 1 and 2 toxicities included 38% headache, 38% flushing, 46% fatigue, 46% anorexia/nausea, and 23% diarrhea. One patient (8%) had both Grade 3–4 headache and fatigue. One patient (8%) had Grade 3–4 diarrhea and another (8%) had a Grade 3 pleural effusion. Hematologic toxicities included neutropenia in 76%, (grade 3-4 63%), thrombocytopenia in 44% (grade 3–4 22%), and 80% with Grade 1–2 anemia. Eleven patients were evaluable for response. No patient achieved CR or PR based on NCI-WG Criteria. Several patients showed evidence of biologic activity of dasatinib including 1 PR in nodes but worsening anemia, 1 stable disease for 3 cycles, and 2 patients with significant reductions in ALC; one patient had a drop from 76,000/ml to 32,000/ml after only 2 days of dasatinib but stopped therapy because of headache, one had a reduction in WBC from 40,000 to 6,000. One patient continues on therapy. In this trial dasatinib produced no responses by NGI-WG criteria but showed evidence of biologic activity in a very heavily pretreated group of pts with CLL. Accrual continues.

Phase II trial of irinotecan plus bevacizumab for heavily pretreated recurrent ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5016-5016
Author(s):  
Salvia Sanjay Jain ◽  
Yan G. Makeyev ◽  
Franco Muggia ◽  
James L. Speyer ◽  
John Patrick Curtin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Protocol Amendment ◽  
Platinum Sensitive ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

5016 Background: Irinotecan and bevacizumab have single agent activity in platinum sensitive (PSen) and resistant (PRes) ovarian cancer patients (pts). We sought to evaluate the efficacy and toxicity of irinotecan plus bevacizumab in these pts. The trial was designed to evaluate whether the progression free survival (PFS) at 6 months is at least 40% and with secondary objectives of estimating response rate (RR), duration of response (DoR), time to progression and toxicity. Methods: No limitation on number of prior regimens was placed, and prior use of study drugs was allowed. Irinotecan 250mg/m2 and bevacizumab 15mg/kg every 3 weeks were given. Due to treatment-related grade 3 toxicity (diarrhea and neutropenia) experienced by the first 5 pts on the study, the dose of irinotecan was amended to 175mg/m2. Results: 20 pts with recurrent ovarian cancer [PSen 5, PRes 15] of a planned 35 have been recruited thus far. Median age is 59 (45-78). Median number of prior regimens is 5 (3-12) with 9 pts demonstrating progressive disease (PD) on prior topotecan-containing regimens and 7 pts exhibiting PD on prior bevacizumab-containing regimens. 4 pts discontinued treatment before 2 cycles (2 for protocol defined toxicity, 2 by patient/physician choice). Partial response (PR) was observed in 2 PSen pts and 1 PRes pt, while stable disease (SD)was seen in 9 (2 PSen, 7 PRes) out of the 15 pts assessable for response at this time. 3 pts demonstrated PD after 2 cycles of treatment. 12 of 13 pts with PR or SD by RECIST also had response by CA125 criteria. Median DoR thus far (SD plus PR) is 18 weeks (4-37). 6 pts have ongoing response (4-18 weeks). Of 19 pts that received > 2 cycles, 3 had grade 3 diarrhea (2 before protocol amendment and 1 after). 2 pts had grade 3/4 neutropenia (1 before and 1 after protocol amendment). Median PFS is 9.6 months (mts). Median overall survival is 15.5 mts. PFS rate at 6 mts is 61% with 95% confidence interval: (40%, 92%). Conclusions: Results of the trial to date suggest the hypothesis that the PFS at 6 mts is less than 40% can be rejected. Activity of this regimen is encouraging given the heavily pretreated nature of the pts. Dose-limiting diarrhea and neutropenia required protocol amendment. We continue to accrue study subjects at the amended dosing.

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