Phase II study of sorafenib and docetaxel in men with metastatic castration resistant prostate cancer (mCRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16055-e16055
Author(s):  
J. P. Cetnar ◽  
M. A. Rosen ◽  
D. J. Vaughn ◽  
N. B. Haas ◽  
A. B. Troxel ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Bone Lesions ◽  
Complete Disappearance ◽  
Castration Resistant Prostate Cancer ◽  
Dce Mri ◽  
Hand Foot Syndrome ◽  
Psa Response ◽  
Grade 3

e16055 Background: Previous trials of the antiangiogenic kinase inhibitor sorafenib in mCRPC have reported PSA elevation accompanying radiographic response, and evidence that sorafenib may potentiate docetaxel (dxl) myelosuppression. To assess the safety, antivascular effects, and activity of sorafenib and dxl in mCRPC, a phase II trial with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) was conducted. Methods: Eligible men had mCRPC and no prior chemotherapy. Treatment consisted of dxl 75 mg/m2(day 1) and sorafenib (days 2–19) of a 21 day cycle. Patients received 7 days of sorafenib before cycle 1. Six patients received sorafenib 200mg BID and remaining patients received sorafenib 400 mg BID if <4/6 patients had grade 4 neutropenia. DCE-MRI was performed at baseline, days 8 and 28. The primary endpoint was PSA response rate (>50% PSA decline). Secondary endpoints were vascular response rate (>20% decline in area under the gadolinium curve [AUC60]), toxicity rates, and time to progression (TTP). PSA-only progression (2 consecutive PSA rises) was confirmed by a third PSA rise or radiographic progression after a 21-day drug holiday. Sample size of 69 patients in 1 stage was designed to maximize detection of significant correlations between DCE-MRI and clinical outcomes. Results: Six of 13 enrolled patients (46%) had a PSA response. A median PSA increase of 37% was observed in 73% of patients after 1 week of sorafenib. The median TTP was 8+ months. Two patients had complete disappearance of bone lesions. Grade 3 adverse events were neutropenia (77%), hand-foot syndrome (23%), anemia (15%), nausea (8%), and rash (8%). A median AUC60 decline of 40% from baseline was observed after 7 days of sorafenib, and only a 6% decline on day 28 during a scheduled sorafenib holiday. Conclusions: Sorafenib 400 mg po bid and dxl 75 mg/m2 are tolerable in men with mCRPC. Elevated PSA values in men treated with sorafenib and dxl does not always reflect disease progression. DCE-MRI can capture sorafenib's impairment of tumor vasculature in osseous metastases and rebound angiogenesis during drug holidays. Bone responses and TTP data provide evidence of encouraging activity. No significant financial relationships to disclose.

Effect of sorafenib on chemotherapy resistance and refractoriness in castration-resistant prostate cancer (CRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16105-e16105
Author(s):  
C. Nabhan ◽  
K. Tolzien ◽  
T. M. Lestingi ◽  
A. Galvez ◽  
J. D. Bitran
Keyword(s):  
Clinical Benefit ◽  
Kinase Inhibitor ◽  
Chemotherapy Resistance ◽  
Complete Response ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Chemotherapy Agent ◽  
Hand Foot Syndrome ◽  
Psa Response ◽  
Grade 3

e16105 Background: There is no standard for CRPC once chemotherapy fails. In studies employing docetaxel (D), 35–39% of pts did not complete therapy due to progression and only 45–50% had a PSA response. This implies that many pts develop resistance to D. Sorafenib is a multi kinase inhibitor with antiangiogenesis properties. We hypothesized that sorafenib could overcome chemotherapy resistance in these pts. Methods: Eligible pts must have progressed while on either D or mitoxantrone (M). They received sorafenib at 400 mg orally twice/daily in addition to the chemotherapy agent they were on. Sorefinib/chemotherapy combination was given for a maximum of 6 cycles followed by sorafenib monotherapy until progression. Primary end point was safety of the sorafenib/chemotherapy combination. Secondary end points included the overall clinical benefit calculated as the sum of complete response (CR), partial response (PR), and stable disease (SD), toxicity, and time to disease progression (TTP). Results: To date, 15 pts have been enrolled; 14 are evaluable. Eleven pts were on D and 4 on M. Median age was 68 (range 61–83), median PSA was 111.2 ng/ml (13.6–1703.9). Nine pts (60%) had visceral and bone disease. Median PSA-DT pre-study was 2 months (0.5–6) and median time from last chemotherapy to starting study was 4 weeks. Median number of given cycles was 6.5 (2–12). Six pts did not require dose reduction, 2 others were re-escalated to the full dose. Sorafenib was safely combined with chemotherapy with 6 pts experiencing grade 3 fatigue, 3 developing grade 3 hand/foot syndrome, and 1 experiening grade 3 diarrhea. Eleven pts (73%) had SD radiographically that lasted a median of 6.7 months. In all, 6 out of 14 pts (42%) had a PSA decline after adding sorafenib and 3 (21%) had stable PSA. Of these 9 pts (PR+SD), 2 never doubled their PSA. Two pts had PSA decline after withdrawing sorafenib. Median TTP for PSA was 3.75 months. PSA responses did not correlate with radiographic changes or clinical benefit. With a median follow-up of 8 months, 5 pts (33%) remain alive with 1 continuing on therapy without progression. Conclusions: Sorafenib overcomes chemotherapy-refractoriness and failures in CRPC. [Table: see text]

A phase II study of sunitinib (SU) for maintenance therapy in metastatic castration-resistant prostate cancer (mCRPC) after response to docetaxel (D).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 151-151 ◽  
Author(s):  
B. J. Eigl ◽  
M. G. Trudeau ◽  
E. Winquist ◽  
K. N. Chi ◽  
M. Eliasziw ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Phase Ii ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Castration Resistant ◽  
Hand Foot Syndrome ◽  
Psa Response ◽  
Psa Progression ◽  
The Mean ◽  
Grade 3

151 Background: After treatment with D based chemotherapy, there is currently no standard therapy although new options are emerging. Due to its mechanism of action, acceptable toxicity profile and simple administration, SU has potential for therapeutic activity in the setting of maintenance therapy for patients with mCRPC who have responded to D based chemotherapy. Methods: Patients with mCRPC who had evidence of responding or stable disease at completion of D treatment were enrolled in this phase II multicentre trial. Patients received 50mg of SU daily on 4 week on/2 week off cycles. The primary endpoint was effect of SU maintenance on PFS. Because of potential effects of SU on PSA kinetics, clinical progression was defined independent of PSA. PSA response rate was a secondary endpoint. PSA-progression (PSA-P) was defined as a 25% PSA increase over baseline. Results: Thirteen patients have been enrolled and treated to date. Mean age was 63 years (47-76). ECOG scores of 0, 1, and 2 were reported for 4, 8 and 1 patients respectively. Mean number of prior cycles of D given was 9.5. A total of 28 cycles of SU were administered. A total of 291 adverse events (AEs) were recorded, of which 66%, 27%, and 7% were classified as Grades 1, 2, and 3, respectively. No Grade 4 AEs were seen. AEs were of a type and severity expected for SU. The most frequent grade 3 AEs were fatigue (n=3) and hand foot syndrome (n=3). No PSA responses have been documented. Most patients had immediate PSA increases without evidence of clinical progression. The mean PSAs increased by 159%, 396%, and 853% in Cycles 1, 2, and 3, respectively, corresponding to p-values of 0.18, 0.03, and 0.01 when compared to the PSA-P threshold of 25%. The trial will continue to complete its planned accrual of 26 evaluable patients and updated results, along with PFS, will be presented at the meeting. Conclusions: SU is well tolerated as maintenance therapy after D in men with mCRPC, with a predictable side-effect profile. PSA values after treatment with SU may not reflect progression in patients with mCRPCas significant increases were observed as early as Cycle 2 without clinical evidence of worsening disease. [Table: see text]

Phase II study of cabozantinib (cabo) in patients (pts) with recurrent/metastatic endometrial cancer (EC): A study of the Princess Margaret, Chicago, and California phase II consortia.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5524-5524 ◽  
Author(s):  
Neesha C. Dhani ◽  
Hal W. Hirte ◽  
Julia V. Burnier ◽  
Angela Jain ◽  
Marcus O. Butler ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Mutational Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Current Data ◽  
Pik3ca Mutations ◽  
Primary Endpoints ◽  
Hand Foot Syndrome ◽  
Grade 3

5524 Background: Recurrent/metastatic EC has a poor prognosis with no standard 2ndline therapy. Cabo is a multi-targeted kinase inhibitor of MET, VEGFR, TIE2, AXL & KIT, relevant in epithelial-stromal cross-talk. The role of MET/HGF in aggressive EC biology, where transient benefit of VEGF-targeting is due to MET/HGF, TIE2 & AXL, provides rationale for MET targeting in EC. Methods: PHL86 (NCI#9322/NCT01935934) is a multi-centre, phase II trial of cabo (60mg oral daily dose) in pts with EC recurring within a year of adjuvant chemotherapy (ctx), or with progression after 1 line of ctx for metastatic disease. Experimental (E) cohort was stratified by histology (serous (SER) vs endometroid (END)) in a Simon two-stage design for co-primary endpoints of response rate ( > 30%) & 12-week progression-free-survival (PFS) ( > 55%). Activity was defined as > 7 partial responses (PRs) or > 15 instances of 12 wk-PFS in 36 pts. Pts with rare histology EC were treated in a parallel exploratory (Ex) cohort. Results: From May 2013 to Nov 2016, 102 pts (E: 71; Ex: 31) have been treated with cabo after prior radiation (59) and/or ctx (no. lines: 1(77); 2(22)). Cabo was well tolerated with common toxicities of fatigue, nausea, diarrhea & hand-foot syndrome. Most frequent Grade 3/4 toxicity was hypertension (32/101 pts). Fistula/perforation occurred in 4 of 71 SER/END pts & 4 of 31 Ex pts; no risk factors were identified. In 33 END pts, 6 PRs & 24 instances of > 12-wk PFS were observed; median PFS is 4.8 mths (95% CI: 4.4 – 6.4) with estimated 6-mth PFS of 43% (95% CI: 27 to 59%). In 34 SER pts, 4 PRs & 20 instances of > 12-wk PFS were observed; median PFS is 4.0 mths (95% CI: 2.7 – 4.7) with estimated 6-mth PFS of 30% (95% CI: 15 to 46%). 4 pts have had PFS > 12 mths, 1 SER pt remains on study after 25mths. Mutational analysis demonstrated presence of KRAS with PTEN or PIK3CA mutations in 9 (SER/END) pts, of whom 8/9 pts met 12-wk PFS endpoint, with a median PFS 5.9 mth (4.1 to 15.4). Conclusions: Cabo has single agent activity in END and SER EC with durable disease control. Concurrent mutation in KRAS/PTEN/PIK3CA may enrich for response. The current data support further evaluation of cabo in EC. Clinical trial information: NCT01935934.

Second-line pemetrexed (P) for the treatment of hormone refractory prostate cancer (HRPC): A Hoosier Oncology Group phase II study—Preliminary analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4644-4644 ◽  
Author(s):  
N. M. Hahn ◽  
C. Whalen ◽  
C. J. Sweeney
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Preliminary Analysis ◽  
Response Rate ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Stopping Rules ◽  
Psa Response ◽  
Grade 3 ◽  
Baseline Psa

4644 Background: We evaluated the efficacy and toxicity of pemetrexed in men with HRPC who had progressed on one prior taxane chemotherapy regimen. Methods: Patients with HRPC received P 500 mg/m2 IV d1 q21d cycle with B12 and folate supplementation until progression or dose-limiting toxicity. The primary outcome measure was PSA response rate (PSAr) defined as a > 50% decline from baseline PSA that was confirmed at least four weeks later. Pts were required to have documented PSA progression prior. If no metastatic disease, a PSA > 20 ng/dL was required. A two-stage Simon phase II design with early stopping rules is being utilized with a PSA response rate of 20% deemed to be clinically relevant. Results: Patient characteristics: To date, 21 of the planned 42 patients have been treated with a median age of 67 years (53–79), median baseline PSA 97.8 (0.7–754.3), and median Karnofsky performance status of 90 (70–100). Treatment Cycles: A total of 83 treatment cycles have been administered with a median of 3 cycles per patient (0–12). Toxicity: 6 of 21 (28.6%) patients experienced a total of 17 grade 3 events. Treatment related grade 3 events included thrombocytopenia (1), anemia (2), mucositis (1), rash (1), and fatigue (1). 3 of 21 (14.3%) patients experienced a total of 8 grade 4 events. Treatment related grade 4 events included neutropenia (2), thrombocytopenia (3), anemia (1), and neutropenic fever (1). Response: Best response observed included 4 PSAr (19.0%, 95% CI 2.2–35.8%), 8 stable disease (SD) (38.1%, 95% CI 17.3–58.8%) and 9 progressive disease (PD) (42.9%, 95% CI 21.7–64.1%). PSAr were maintained at 5, 12+, 5+, and 3+ weeks with sustained SD seen at 15, 12, 15, 21+, 18+, and 12+ weeks. Survival data is immature at this time. Conclusion: This preliminary analysis reveals that pemetrexed has met criteria to move into the second stage of the study and has an acceptable toxicity profile in this patient population. [Table: see text]

Phase II trial of oral capecitabine (C) and weekly docetaxel (D) in patients with metastatic androgen independent prostate cancer (AIPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5121-5121 ◽  
Author(s):  
S. Marur ◽  
J. Eliason ◽  
L. Heilbrun ◽  
D. Smith ◽  
B. Dickow ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Tissue ◽  
Phase Ii Trial ◽  
Dihydropyrimidine Dehydrogenase ◽  
Final Analysis ◽  
Biomarker Analysis ◽  
Measurable Disease ◽  
Hand Foot Syndrome ◽  
Psa Response ◽  
Grade 3

5121 Background: Due to demonstrated synergistic anti-tumor effect of D and C related to docetaxel-mediated up-regulation of thymidine phosphorylase (TP), a phase II trial with weekly D and C in metastatic AIPC was performed. Endpoints of response and survival were correlated with biomarker levels of TP, dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) in tumor tissue and DPD in serum Methods: Patients with metastatic AIPC, with no prior chemotherapy for metastatic disease were eligible to receive D 36 mg/m2/week IV on days 1,8, and 15 and C 1,250 mg/m2 /day in two divided doses on days 5–18. Cycles were repeated every 28 days and response was assessed every 2 cycles. Biomarker correlative study for Serum DPD and TP/DPD ratio and TS/DPD ratio on tissue were performed using mouse anti-TP, rat anti-DPD and mouse anti-TS monoclonal antibodies Results: 30 patients enrolled with median age of 69 years, median pretherapy PSA of 110 ng/ml (range 1.2 to 3716.9). 21(70%) had bone pain, Gleason score ≥ 8 in 18 (61%) patients; measurable disease progression in 9, bone scan progression in 18 patients and PSA only progression noted in 22 patients. 144 cycles have been administered (range 0–10 cycles). Grade 3 or 4 neutropenia seen in 3 patients and Grade 3 hand-foot syndrome in 2 patients. No treatment related deaths seen. PSA response (≥50% decline) noted in 22 (73.3%) with ≥90% PSA decline in 9 (30%) pts. Measurable disease PR noted in 5 of 9 patients (56 %). Median follow-up is 11 months (range 2.1 to 30.4). Median time to progression is 9.1 months (90% CI 6.2–15.1 months), and the median overall survival (OS) is 18.9 months (90% CI 14.9–26.4 months). 1 year PFS and OS is 44% and 84% respectively. Samples for DPD were available for 25 patients and pre-therapy tumor tissue for 23 patients. Quantitative fluorescence IHC has been performed on available samples, the final analysis is ongoing. Conclusions: The combination is well tolerated and demonstrates favorable and durable remission and survival outcomes. Correlation with biomarker analysis will be reported. This may help in selecting patients more likely to derive benefit from combination of D and C. Supported in part by Aventis Inc. No significant financial relationships to disclose.

Prospective evaluation of low-dose ketoconazole plus hydrocortisone (HC) in chemotherapy-pretreated castration-resistant prostate cancer (CRPC) patients.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 227-227
Author(s):  
Ernest N. Lo ◽  
Laurel A. Beckett ◽  
Chong-xian Pan ◽  
Daniel Robles ◽  
Jennifer Marie Suga ◽  
...  
Keyword(s):  
Stable Disease ◽  
Low Dose ◽  
Response Rate ◽  
Randomized Study ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Published Data ◽  
Castration Resistant Prostate Cancer ◽  
Psa Response ◽  
Grade 3

227 Background: Ketoconazole (keto), a known CYP17 inhibitor, is a traditional systemic treatment for CRPC. However, most of the published data has been in the pre-chemo setting; its efficacy in the post-chemo setting has not been as widely reported. Chemo-naive patients treated with attenuated doses of keto (200-300 mg TID) had prostate specific antigen (PSA) response rate (> 50% decline) ranges from 21%-62% and treatment was well tolerated. We hypothesized that low dose keto would likewise possess efficacy and tolerability in the CRPC post-chemo state. Methods: CRPC patients with ECOG PS 0-3, adequate end organ function, who had received at least one chemo were treated with low-dose keto (200 mg PO TID) and HC (20 mg PO q AM and 10 mg PO q PM) until progression, as defined by either RECIST or PSA rise > 50% from nadir or baseline. Primary endpoint was PSA response rate (> 50% reduction from baseline). A Simon minimax design was used. PSA response of > 25% was to be considered promising for further study (versus null rate of < 5%); 25 patients were required. Secondary endpoints included PSA response > 30%, progression-free survival (PFS), duration of stable disease, and evaluation of adverse events (AE). Results: 29 patients were accrued: median age was 71 (range 55-86) and median pretreatment PSA was 76 ng/mL (range 7-11,420 ng/ml); all had prior docetaxel-based chemotherapy. 28 patients were evaluable for response; all were evaluable for toxicity. PSA response of >50% was seen in 48% of patients and 59% of patients had a PSA response of > 30%. Median PFS was 138 days; median duration of stable disease was 123 days. 12 patients had grade 3 or 4 toxicity on treatment. Of the 17 grade 3 AEs, only 3 were considered ‘probably’ or ‘possibly’ related to treatment, while none of the 2 grade 4 AEs were considered related to treatment. Conclusions: In docetaxel pre-treated CRPC patients, low-dose keto + HC is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response with low-dose keto appears comparable to that of abiraterone in this patient context. A prospective randomized study of available post-chemo options is needed to assess comparative efficacy. Clinical trial information: NCT00895310.

Phase II study of cabazitaxel (CAB) plus enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 86-86
Author(s):  
Julie Nicole Graff ◽  
Heather H. Cheng ◽  
Jacqueline Vuky ◽  
Joshi J. Alumkal ◽  
Dustin Kreitner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Single Agent ◽  
Failure To Thrive ◽  
Castration Resistant Prostate Cancer ◽  
Eligibility Criteria ◽  
Psa Response ◽  
Pre Treatment ◽  
Grade 3

86 Background: There are six agents that improve survival in mCRPC, each administered as a single agent. Combinations of agents with distinct mechanisms of action have the potential to improve outcomes. Methods: We performed a multi-institution phase I/II study to examine safety and efficacy of CAB plus ENZ with mandatory granulocyte-colony stimulating factor support in mCRPC. Results: A sample size of 3 to 12 subjects for the phase I portion and 33 for the phase II portion provided 82% power to detect PSA response rate (decrease ≥90%) of 50% compared to the null hypothesis of 24%. The main eligibility criteria allowed prior abiraterone/prednisone (AAP) and docetaxel (in the metastatic hormone sensitive setting). Baseline characteristics: median age 69 years (47 - 82), median PSA 20.2 ng/dl (0.2 - 966.3); 7 subjects had visceral disease, 10 received prior AAP, and 8 received prior docetaxel. In the phase I portion, there were no dose limiting toxicities using CAB 25 mg/m2 IV Q3wks up to 10 cycles and ENZ 160 mg PO QD, hence this dosing was used for the phase II portion. 33 men with mCRPC were treated with CAB plus ENZ in the phase II arm. PSA response rates are listed in Table. Prior exposure to AAP decreased PSA response, but subjects who had prior AAP also had higher pre-treatment PSA. There were no treatment related deaths. Dose reduction of CAB to 20 mg/m2 was needed in 7 subjects. Over the course of the study, 14 Grade 3 adverse events occurred that were deemed possibly related to treatment: fatigue (n=2, 6%), febrile neutropenia (n=2, 6%), leukopenia (n=2, 6%), thrombocytopenia (n=2, 6%), anemia (n=1, 3%), hypertension (n=1, 3%), leukocytosis (n=2, 6%), fracture (n=1, 3%), failure to thrive (n=1, 3%). Conclusions: CAB plus ENZ was tolerable and associated with promising anti-tumor activity, particularly in abiraterone-naïve subjects. Further evaluation of this regimen is warranted. This project was managed by the Prostate Cancer Clinical Trials Consortium and funded by Astellas Inc. and Sanofi. Clinical trial information: NCT02522715. [Table: see text]

Phase II trial of nab-paclitaxel (nanoparticle albumin-bound paclitaxel (ABX)) + capecitabine (XEL) in first-line treatment of metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1053-1053 ◽  
Author(s):  
B. G. Somer ◽  
L. S. Schwartzberg ◽  
F. Arena ◽  
A. Epperson ◽  
D. Fu ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Safety And Efficacy ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Dose Reductions

1053 Background: ABX and XEL both have substantial single agent activity in MBC. Taxane and anti-metabolite doublets improve response rate and TTP and longer survival. ABX administered weekly has an excellent safety and efficacy profile with maintenance of dose intensity. This study was designed to test the safety and efficacy of ABX + XEL given in a novel combination schedule. Methods: This phase II, multicenter open label study utilized ABX 125 mg/m2 IV on day 1, 8 and with no premeds and capecitabine 825 mg/m2 PO BID days 1–14 on a Q 3 week cycle. The primary endpoint is objective response rate, with evaluation performed after every 2 cycles. Entry criteria include measurable MBC by RECIST criteria, age >18, PS 0–2, no prior chemo for metastatic disease, > 6 months since adjuvant fluoropyrimidine and/or paclitaxel. Results: The full sample of 50 patients (pts) have been enrolled; data from 43 pts are available for analysis. Median age is 58 (range 23.7–90.6). 37% received prior adjuvant anthracycline and 33% prior adjuvant taxane. Median number of metastatic sites is 2 (range 1–7), with most common sites of disease liver, 53.5%; bone, 51.2%; and lung, 14%. 226 cycles of therapy have been delivered. 5 pts required a dose reduction in XEL (3 pts to 650 mg/m2; 2 to 550 mg/m2) and 4 pts had dose reduction in ABX to 100 mg/m2. XEL dose reductions occurred due to hand-foot syndrome (3), neutropenia (1), and fatigue (1). ABX dose reductions occurred due to mucositis, diarrhea, fatigue, and neuropathy (1 pt each). 10 pts had grade 3–4 non-hematologic AEs: 3 hand-foot syndrome, 4 fatigue, and 3 GI. Hematologic AEs included 4 with grade 3 and 1 with grade 4 neutropenia, and 2 with grade 4 febrile neutropenia. The most common AEs of any grade were GI (30), dermatological (23), fatigue (15), neuropathy (12), and hand-foot syndrome (11). The incidence of Grade 1–2 neuropathy was 25% (no grade 3–4). Of 38 pts available for analysis of response, the overall response rate is 47.5%: PR 39.5%, CR 8%. Total of 15 pts have stable disease, 20 pts have completed 6+ cycles. No significant financial relationships to disclose.

Phase II study of infusional 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4089-4089 ◽  
Author(s):  
S. Kopetz ◽  
K. Y. Glover ◽  
C. Eng ◽  
R. A. Wolff ◽  
D. Z. Chang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Intention To Treat ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
First Line Treatment

4089 Background: When compared to bolus 5-fluorouracil (F), leucovorin (L), and irinotecan (I) regimens such as IFL, the infusional F, L, I regimen (FOLFIRI) resulted in a improved toxicity profile with a response rate (RR) of 35% and median progression free survival (PFS) of 6.7 months. When combined with bevacizumab (B) as first-line treatment, IFL demonstrated improved activity with a RR of 45% and a median PFS of 10.6 months. Combining FOLFIRI and B may further improve the efficacy. Methods: We designed a single-arm, phase II trial of FOLFIRI+B with B (5mg/kg), I (180mg/m2), bolus of F (400mg/m2) and L (400mg/m2) with a 46-hour infusion of F (2400mg/m2) every 2 weeks. The primary endpoint was PFS. Chemotherapy naïve mCRC patients (pts) with a performance status of 0–2 received B alone on Day -14, starting FOLFIRI+B on Day 1. Proteomic and radiographic correlative studies were completed and will be reported separately. Results: N=41 pts, median age 56 y/o (range 26–78), M:F = 16:25, 5 pts with prior adjuvant therapy, were enrolled from 1/2005 to 1/2007. A total of 502 cycles have been administered (median = 12). The median PFS is 12.6 months. Response rate by intention-to-treat analysis was 62% (24 pts), with 33% stable disease (13 pts). Responses occurred after a median of 4 months of therapy. Fifteen pts remain on treatment; 26 pts are off study: 7 for progressive disease, 2 withdrew consent, 7 for toxicity and 2 for surgery unrelated to cancer. Eight pts were removed from the study for metastasectomies. Grade 3 or 4 toxicities included 17 occurrences of grade = 3 neutropenia, including 1 grade 4 febrile neutropenia, 4 grade 4 pulmonary emboli, 2 grade 3 hand-foot syndrome, and 1 grade 3 diarrhea. One pt included in the analysis developed a possible microperforation, manifested by peritonitis, after B alone and never received FOLFIRI. Conclusion: FOLFIRI+B is well-tolerated and efficacious, with an impressive PFS that compares favorably to historical controls. This regimen is an excellent choice as a first-line treatment for mCRC. No significant financial relationships to disclose.

SWOG S0354: A phase II trial of CNTO328, a monoclonal antibody against interleukin-6 (IL-6), in chemotherapy pretreated patients (pts) with castration- resistant prostate cancer (CRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5143-5143
Author(s):  
J. K. Pinski ◽  
B. Goldman ◽  
T. Dorff ◽  
P. Mack ◽  
P. Lara ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Castration Resistant Prostate Cancer ◽  
Plasma Cytokines ◽  
Cancer Cell Survival ◽  
Psa Response ◽  
Pleiotrophic Effects ◽  
Grade 3

5143 Background: IL-6 facilitates cancer cell survival via pleiotrophic effects on proliferation, apoptosis, angiogenesis, differentiation, and chemo-resistance. A multicenter phase II study of CNTO328 in chemo pretreated CRPC pts was conducted. Methods: Eligible pts had one prior chemotherapy, Zubrod performance status 0–2, and adequate end-organ function. Regimen: CNTO328 6 mg/kg IV q2 weeks x 12 cycles. Response assessment was q6 weeks. Primary endpoint was PSA response rate (RR) defined as ≥50% reduction. Accrual was completed in 2 stages, with planned accrual of 20 eligible pts in the first stage and 40 overall. Plasma cytokines were measured by Luminex in 44 pts. Results: Of 62 pts, 54 were eligible; all had received prior taxane therapy. Two (3.7%; 95% CI: 0.5%, 12.8%) had PSA response. Of 47 pts evaluable by RECIST, none had a response and 10 (21%) had stable disease (SD). With median follow-up of 6.6 months, median progression-free survival is 1.6 months (95% CI: 1.6, 1.7). Grade 4 toxicity included 1 case of DIC and 1 CNS ischemia; grade 3 toxicities included elevated AST (1), gastritis/esophagitis (2), thrombocytopenia (2), pain (2), leucopenia (1), and neuropathy (2). Median baseline IL-6 levels were 12.5 pg/mL (IQR: 2.5, 41.5). Pts with levels >12.5 pg/mL had worse 6-month survival vs. < 12.5 pg/mL (53% vs 94%, p = 0.02). Post-cycle 1, IL-6 levels were > 250-fold higher, indicating antibody-target complex formation. 33/39 pts had a decline in C-reactive protein (CRP) plasma levels at 6 weeks. Conclusions: CNTO328 was well-tolerated and resulted in a PSA RR of 3.7% and RECIST SD rate of 21%. Declining CRP levels during treatment reflect biologic activity. Elevated baseline IL-6 levels portend a poor prognosis. Additional translational studies will be presented. Additional study of CNTO328 in combination may be warranted. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document