Final results of a University of Chicago phase II consortium trial of sorafenib (SOR) in patients (pts) with imatinib (IM)- and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
N. P. Campbell ◽  
K. Wroblewski ◽  
R. G. Maki ◽  
D. R. D'Adamo ◽  
W. A. Chow ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Stage Design ◽  
Fda Approval ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Gi Bleed

4 Background: GIST pts who develop resistance to IM and SU have few therapeutic options. SOR inhibits KIT, VEGFR, PDGFR-β, and BRAF kinases. In preclinical models, SOR has activity against several IM-RES mutations that are resistant to SU (Heinrich. ASCO 2009). Methods: We performed a multi-center, phase II trial of SOR in unresectable, KIT-expressing GIST pts who had disease progression on IM by RECIST. After FDA approval of SU for IM-RES GIST, the study was amended in 2/07 to require progression after both IM and SU. Pts received SOR 400 mg orally twice daily. CT scans were obtained Q2 28-day cycles. The primary endpoint was objective response rate. A Simon minimax 2-stage design required 1 response in 18 pts to proceed to a second stage, and 4 responses in 32 IM/SU RES pts for further investigation. Results: 38 pts (6 IM-RES, 32 IM/SU-RES) enrolled 1/06-9/09 at 6 centers. Median follow-up for survivors: 31 months (mo). Pt characteristics: male 55%; median age 57 (range 42-85); PS 0/1/2: 47%/47%/6%. Median cycles: 4 (range 1-37). 63% pts had at least 1 dose reduction. Partial response (PR): 13% (1 IM-RES, 4 IM/SU-RES); stable disease (SD): 55% (3 IM-RES, 18 IM/SU-RES). Disease control rate (PR + SD): 68%. Median progression-free survival: 5.2 mo (95% CI: 3.4, 7.4). Median overall survival 11.6 mo (95% CI: 8.8, 18.0); 1-year survival 50%; 2-year survival 29%. Three pts remain on trial receiving study drug (1 PR at 34 mo; 2 SD at 18 and 37 mo). Grade 3/4 toxicities (% pts): hand-foot syndrome 45%, hypertension 21%, diarrhea 8%, hypophosphatemia 8%, GI bleed 5%, rash 5%, thrombosis 3%, GI perforation 3%, fatigue 3%, anemia 3%. Conclusions: SOR is active in IM-and SU-resistant GIST. Some pts treated with SOR experience prolonged disease control. SOR is well-tolerated in GIST pts, but dose reductions are often required. SOR warrants further investigation in GIST. Supported by NCI grant N01-CM-62201. [Table: see text]

151 A RANDOMIZED,OPEN CLINICAL TRIAL TO COMPARE THE EFFICACY AND SAFETY OF ANLOTINIB PLUS IRINOTECAN VERSUS IRINOTECAN IN PATIENTS WITH ESCC

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Xiangrui Meng ◽  
Hangrui Liu ◽  
Qingxia Fan
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Thyroid Stimulating Hormone ◽  
Disease Control Rate ◽  
Control Group ◽  
Trial Group ◽  
Grade 3

Abstract   The benefit of systemic treatment in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain. Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferation. A phase II trial (NCT02649361) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in refractory metastatic ESCC. This study (NCT03387904) aimed at comparing the effects and safety of Anlotinib Plus Irinotecan versus Irinotecan in patients with ESCC. Methods We conducted a prospective randomized, multicenter, phase II trial to compare the efficacy of Anlotinib Plus Irinotecan with Irinotecan in recurrent ESCC patients who had resistance to platinum or taxane-based chemotherapy. Eligible patients were adults with pathologically confirmed recurrent ESCC, and 82 patients were randomized 1:1 to Irinotecan (65 mg/m2/day 1 and day 8) with or without anlotinib (12 mg qd day 1 to 14) of a 21-day cycle till progression or intolerable. The primary endpoint is the disease control rate (DCR) and progression-free survival (PFS) and the secondary end points are objective response rate (ORR) and overall survival (OS). Results Between 13/1 2019 and 20/1 2020, a total of 43 patients were enrolled and randomly assigned to either the anlotinib plus irinotecan (n = 22) or the irinotecan group (n = 21).The mPFS was longer in trial group than in control group (89 days vs 66 days, HR = 0.447, P = 0.055). The Disease control rate (DCR) was 54.5% in trial group and 38.1% in the control group. The treatment-related adverse events (>10%) were fatigue (59.1%), nausea (50.0%), decreased appetite (36.4%), hoarseness (27.3%), thyroid-stimulating hormone elevation (22.7%), diarrhea (9.1%), and decreased lymphocytes count(9.1%) in trial group. Grade 3 AEs included fatigue (4.5% vs 4.8%), nausea (4.5% vs 0%) and diarrhea (4.5% vs 0%) in two groups. Conclusion Anlotinib plus irinotecan was similarly tolerable but prolonged PFS compared to irinotecan monotherapy as a second-line treatment in patients with recurrent ESCC.

Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11565-11565
Author(s):  
Scott Schuetze ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

Association of statins and nivolumab activity in patients with metastatic renal cell carcinoma (mRCC): Results from the phase II nivoren—GETUG AFU 26 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 359-359
Author(s):  
Emeline Colomba ◽  
Ronan Flippot ◽  
Cécile Dalban ◽  
Sylvie Negrier ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Modulation ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Population Based ◽  
Metabolic Reprogramming ◽  
Oncogenic Signaling ◽  
Grade 3 ◽  
The Impact

359 Background: Statins are HMG-CoA inhibitors that regulate several mechanisms involved in tumor growth, including mitochondrial metabolism, activation of oncogenic signaling pathways, and immune modulation. Population-based studies showed that statin intake may be negatively associated with RCC onset. The impact of statins on response to immunotherapy in mRCC is unknown. Herein we study the association between statin administration and outcomes in patients with mRCC treated with nivolumab in the NIVOREN-GETUG AFU 26 phase II trial (NCT03013335). Methods: Patients with mRCC who failed previous VEGFR inhibitors were included. We assessed nivolumab activity, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to statin intake at baseline. Toxicity was assessed using CTCAE v4.0. Results: Overall,133 patients were treated with statins at baseline among 702 evaluable for concomitant therapies (19%). Among them, median age was 68 (49-90), 84% were male, 85% had a performance status ≥ 80%, 42% were overweight and 20% obese. Patients treated with statins had mostly good (23%) or intermediate (58%) IMDC risk, 64% had grade 3 or 4 tumors, and nivolumab was given in a third line setting or more in 55%. Median follow-up was 23.9 months (95%CI 23.0-24.5) in the overall cohort. The ORR was 26% in patients treated with statins, PFS 5.0 months (CI95% 3.0 – 5.5), OS 27.9 months (CI95% 19.4-30.3). Outcomes of patients with or without statins did not differ significantly. Similar rates of grade 3-5 TRAE were reported in patients with (20%) or without (18%) statin intake. Conclusions: This is the first study to evaluate statin intake and outcomes with nivolumab in patients with mRCC. Despite numerically higher ORR, statins were not significantly associated with improved outcomes. These data require other analyzes considering other factors such as BMI and other comorbidities. Further studies may help better understand the interplay between immunity and metabolic reprogramming in RCC.

Phase II Study of Pemetrexed Plus Carboplatin in Malignant Pleural Mesothelioma

2006 ◽  
Vol 24 (9) ◽  
pp. 1443-1448 ◽  
Author(s):  
Giovanni L. Ceresoli ◽  
Paolo A. Zucali ◽  
Adolfo G. Favaretto ◽  
Francesco Grossi ◽  
Paolo Bidoli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Control ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Objective Response ◽  
Dose Intensity ◽  
Pleural Mesothelioma ◽  
Standard Regimen ◽  
Time Curve ◽  
Grade 3

Purpose This multicenter, phase II clinical study was conducted to evaluate the activity of the combination of pemetrexed and carboplatin in patients with malignant pleural mesothelioma (MPM). Patients and Methods Chemotherapy-naive patients with measurable disease and adequate organ function, who were not eligible for curative surgery, received pemetrexed 500 mg/m2 and carboplatin area under the plasma concentration-time curve of 5 mg/mL/min, administered intravenously every 21 days. All patients received folic acid and vitamin B12 supplementation. Pemetrexed was provided within the Expanded Access Program. Results A total of 102 patients were enrolled. An objective response was achieved in 19 patients (two complete and 17 partial responses), for a response rate of 18.6% (95% CI, 11.6% to 27.5%). Forty-eight patients (47.0%; 95% CI, 37.1% to 57.2%) had stable disease after treatment. Overall, 67 patients (65.7%) achieved disease control (95% CI, 55.6% to 74.8%). Median time to progression was 6.5 months; median overall survival time was 12.7 months. Compliance to treatment was excellent, with a relative dose-intensity of 97% for pemetrexed and 98% for carboplatin. Toxicity was mild, with grade 3 or 4 neutropenia occurring in 9.7% of total cycles and grade 3 or 4 anemia occurring in 3.5% of total cycles. Nonhematologic toxicity was negligible. Conclusion Treatment with pemetrexed and carboplatin was active and well tolerated in patients with MPM. Disease control rate, time to disease progression, and overall survival were similar to the results achieved with the standard regimen of pemetrexed and cisplatin, suggesting that the carboplatin combination could be an alternative option for these patients.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Ixabepilone, mitoxantrone, and prednisone in patients with metastatic castration-resistant prostate cancer refractory to docetaxel-based therapy: A phase II study of the DOD Prostate Cancer Clinical Trials Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5058-5058
Author(s):  
E. Small ◽  
A. Harzstark ◽  
V. K. Weinberg ◽  
D. C. Smith ◽  
P. Mathew ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Phase Ii ◽  
Vasovagal Syncope ◽  
Objective Response ◽  
Study Drug ◽  
Cancer Clinical Trials ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Grade 3

5058 Background: Mitoxantrone (M) plus prednisone (P) and ixabepilone (Ix) each have modest, non cross-resistant activity as second line chemotherapy regimens in docetaxel-refractory patients with CRPC. These agents were therefore combined in a phase I study which demonstrated anti-cancer activity and defined the recommended phase II dose used in this trial. Methods: Patients with metastatic CRPC and progression after 3 or more cycles of docetaxel were enrolled in a phase II multicenter study of the combination of prednisone 5 mg BID, Ix (35 mg/m2) and M (12 mg/m2) administered intravenously on day 1 every 21 days, with pegfilgrastim (6 mg on day 2) support. Results: To date, 43 pts have been enrolled and have received a median of 4 cycles. Of 37 patients currently evaluable for response, 14 (38%; 95% CI: 22–55%) have had a confirmed ≥50% decline in PSA and 19 (51%; 95% CI 34–68%) have had a confirmed ≥30% decline in PSA. Two of 15 patients with evaluable measurable disease (13%) have had a RECIST-defined objective response. All 43 patients are evaluable for toxicity. Grade 3 or 4 neutropenia was seen in 6 pts (17%) and grade 3 or 4 thrombocytopenia was seen in 3 (8%). Nonhematologic grade 3/4 events possibly related to study drug have included grade 3 fatigue (3 pts), grade 3 pneumonia (2 pts), and grade 3 atrial fibrillation, grade 4 myocardial infarction, grade 4 prostatitis, grade 3 nausea/vomiting, grade 3 neuropathy, grade 3 elevated transaminases, grade 3 dizziness, grade 3 dehydration, grade 3 shortness of breath, and grade 4 vasovagal syncope (1 pt each). Grade 2 neuropathy has been seen in 4 patients. Conclusions: The Ix, M, P regimen is active as second-line therapy in CRPC patients with progressive disease after docetaxel therapy and is reasonably well tolerated. Further investigation of this regimen is warranted. This study was supported in part by CTEP/NCI and the DOD Prostate Cancer Clinical Trials Consortium. [Table: see text]

Irinotecan plus temozolomide in children with recurrent or refractory neuroblastoma: A phase II Children's Oncology Group study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10011-10011
Author(s):  
R. Bagatell ◽  
L. M. Wagner ◽  
S. L. Cohn ◽  
J. M. Maris ◽  
C. P. Reynolds ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Bone Marrow Aspirate ◽  
Response Rate ◽  
Objective Response ◽  
Response Assessment ◽  
Stage Design ◽  
Combination Methods ◽  
Grade 3 ◽  
Experienced Grade

10011 Background: Treatment of children with relapsed or refractory neuroblastoma (NB) remains a challenge. Responses to irinotecan (IRN) + temozolomide (TEM) were seen in NB xenograft-bearing mice, and objective responses were observed in patients with NB treated on a phase I study of this combination. Methods: A phase II study of IRN (10 mg/m2/dose IV daily × 5 days times; 2 weeks) + TEM (100 mg/m2/dose PO daily × 5 days) for children with relapsed or refractory NB was conducted. A one-stage design (endpoint: best overall response) required 5 or more responders out of the first 25 evaluable patients on each of two strata: 1) patients with disease measurable by CT or MRI; and 2) patients with disease detected only by bone marrow aspirate/biopsy and/or MIBG scan. Patients with stable disease or better after 3 cycles could receive an additional 3 cycles of study therapy. International Neuroblastoma Response Criteria were used for response assessment. Radiographic responses were centrally reviewed. Results: Fifty-five eligible and evaluable patients were enrolled, 28 on stratum 1 and 27 on stratum 2. Four responses were observed in the first 25 evaluable stratum 1 patients, and five responses were observed in the first 25 evaluable stratum 2 patients. Three patients had complete responses, but the overall objective response rate (CR+PR) was 16% (9/55). Eleven (stratum 1) and 13 (stratum 2) patients had stable disease. Less than 5% of patients experienced Grade 3 or 4 diarrhea. Although 18% of patients on stratum 1 and 35% of patients on stratum 2 experienced Grade 3 or 4 neutropenia during the first 3 cycles of therapy, <10% of all patients developed evidence of infection while neutropenic. Thrombocytopenia (Grade 3 or 4) was observed in only 7% of patients on stratum 1 and 12% on stratum 2. Conclusions: The combination of IRN+TEM was well tolerated in patients with recurrent or refractory NB. There were 9 objective responses, including 3 complete responses. The minimum desired response rate was attained within stratum 2, but not stratum 1. IRN+TEM may be an appropriate backbone for further study in the relapse setting in combination with novel, targeted agents. No significant financial relationships to disclose.

A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive breast carcinoma: Results after completion of stage I: A trial of the Princess Margaret Hospital Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1133-1133 ◽  
Author(s):  
S. K. Taylor ◽  
S. Chia ◽  
S. Dent ◽  
M. Clemons ◽  
P. Grenci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Progressive Disease ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Grade 3

1133 Background: Pazopanib, an oral small molecule inhibitor of VEGFR, PDGFR, and KIT, has demonstrated activity in phase I, with a recommended phase II dose of 800 mg/d (Hurwitz H et al, J Clin Oncol. 2005;23[16 suppl]:3012.1). We evaluated the activity of single agent pazopanib in recurrent or metastatic breast cancer (MBC). Methods: In this 2-stage design, patients with recurrent or MBC received pazopanib 800 mg/d. The primary endpoint was objective response rate (ORR) of 20%. Response in 3 out of 18 patients was required to go to stage 2. Treatment was continued until progression. Results: 21 patients entered stage 1; 67% were ER positive and all were HER-2-negative. Prior lines of chemotherapy were 1 in 76% and 2 in 14%. Of the 19 evaluable patients, 2 patients remain on treatment. 14 (74%) stopped due to progressive disease, 2 (10%) due to adverse events, and 1 (5%) due to patient request. Best response was partial response (PR) in 1 (5%), stable disease (SD) in 11 (58%), and progressive disease in 7 (37%). Clinical benefit rate (CR, PR, or SD for ≥ 6 months) was 26%. Median time to progression (TTP) was 3.7 months (95% C.I. 1.7 months - not reached). 9 out of 18 patients (50%) with measurable target lesions had some decrease in target lesion size. Estimated progression-free survival at 3 months was 55%, and 28% at 6 months. Adverse events were grade 3/4 elevations in AST (14%) and ALT (10%), and grade 3 hypertension and neutropenia (14% each). Other common events were grade 1/2 lymphopenia, neutropenia, diarrhea, fatigue, skin hypopigmentation, hypertension, nausea, vomiting, anorexia, and headache. Conclusions: Pazopanib is well tolerated and demonstrates activity in pretreated breast cancer. While the target ORR of 20% has not been met, rates of SD and TTP are comparable to other active agents in this setting, and therefore pazopanib may be an interesting agent for future studies in breast cancer. [Table: see text]

Randomized phase II trial of capecitabine versus capecitabine, low molecular weight heparin, and prednisone in refractory colorectal carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15126-e15126 ◽  
Author(s):  
E. Mak ◽  
C. Townsley ◽  
R. Buckman ◽  
E. Chen ◽  
L. Lopez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Previous Treatment ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3

e15126 Background: Capecitabine is widely used in the treatment of advanced colorectal cancer. Continuous low dose chemotherapy has been postulated to have anti-angiogenic effects discrete from its anti-proliferative effects on tumors (metronomic therapy). Dalteparin and prednisone have also been implicated in inhibiting tumour angiogenesis and hypothesized to have additive benefit to chemotherapy. This randomized phase II study examined the additive effect of dalteparin and prednisone with capecitabine in metastatic colorectal cancer. Methods: Patients with metastatic colorectal cancer were randomized to either capecitabine (C) 2,500 mg/m2 in divided doses from days 1–14 in a 3-week cycle or capecitabine with dalteparin and prednisone (CDP). There was no restriction on previous treatment, other than no prior capecitabine. Dalteparin was given at 5,000 units once daily subcutaneously, and prednisone orally 10 mg daily, both on a continuous basis. Thirty patients were planned for accrual in each arm with interim analysis when accrual reached fifteen in each arm. The primary end-point was disease control defined as treatment response or stable disease >4 months. Radiological evaluation was performed every 6 weeks. Treatment was discontinued if patients had progressive disease or intolerable toxicity. Results: Thirty patients were recruited. Fourteen patients had received ≥3 previous regimens (median 3 (C), 2 (CDP)). Median performance statuses were ECOG 1 (C) and 0 (CDP). Nine patients achieved stable disease greater than 6 months (5 (C)/4 (CDP)). There was no statistical difference in the median survival time and time-to- progression for the two groups (11.1 mth (C)/15.8 mth (CDP); 3.2 mth (C)/2.8 mth (CDP)). The commonest toxicities overall were myelosuppression and hand-foot syndrome (HFS). The most common Grade 3+ adverse events were HFS (6 patients) and diarrhea (4 patients). Conclusions: The combination of dalteparin, prednisone and capecitabine did not improve disease control over that seen with capecitabine in refractory metastatic colorectal cancer. No significant financial relationships to disclose.

Efficacy and safety of sunitinib (SU) in patients (pts) with metastatic renal cell carcinoma (mRCC) and lung metastases (mets) only at baseline.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15098-e15098
Author(s):  
Nobuo Shinohara ◽  
Hideyuki Akaza ◽  
Yoshihiko Tomita ◽  
Takeshi Yuasa ◽  
Hiroyuki Fujimoto ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Objective Response ◽  
White Blood Cells ◽  
Progression Free Survival ◽  
Rank Test ◽  
Efficacy And Safety ◽  
Kaplan Meier ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3

e15098 Background: The lungs may be the sole site of mets in RCC.In this retrospective analysis, we analyzed the efficacy and safety of SU in mRCC pts from a global phase (ph) III study and a Japanese ph II study who had lung mets only at baseline. Methods: In the ph III study, treatment (Tx)-naïve mRCC pts were randomized 1:1 to SU 50 mg/d on a 4-weeks-on-2-weeks-off schedule (n=375) or interferon-a (IFN) 9 MU subcutaneously TIW (n=360). In the single-arm ph II study, Tx-naïve (n=25) and cytokine refractory (n=26) mRCC pts received the same SU Tx. In the ph III study, progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, with median values compared by log-rank test. In both studies, objective response rate (ORR) was calculated with a two-sided 95% CI. PFS, OS, ORR, and safety were analyzed at final data cutoff. Results: In the ph III study, 31 (8%) and 42 (11%) pts in the SU and IFN groups, respectively, had lung mets only, compared with 12 (24%) in the ph II study. Baseline characteristics in lung mets pts were similar to all pts. In lung mets pts from the ph III study, ORR was higher with SU than with IFN (58.1% [95% CI: 39.1–75.5] vs. 19.0% [95% CI: 8.6–34.1]; P<0.001); there was a trend for longer median PFS with SU (14.1 vs. 7.8 months; HR: 0.531 [95% CI: 0.278–1.015]; P=0.0513); and median OS was comparable in both Tx subgroups (HR: 0.739 [95% CI: 0.335–1.628]; P=0.4507), although, at 25% of events, median OS was 22.9 months with SU vs. 15.8 months with IFN. In lung mets pts from the ph II study, ORR was 75.0% (95% CI: 42.8–94.5); at the time of analysis, median PFS and OS had not been reached; 4 pts (33%) had died due to any cause and 8 (67%) were alive without disease progression. The most common grade ≥3 SU-related AEs were fatigue, hand-foot syndrome, and diarrhea (all 19%) in the ph III study, and decreased platelets (100%), white blood cells (92%), and neutrophils (92%) in the ph II study. Conclusions: In the ph III study, Tx-naïve mRCC pts with lung mets only had significantly higher ORR and a trend for improved PFS and OS with SU compared with IFN. In the Japanese ph II study, ORR with SU was 75% in lung mets pts. Thus, 1st-line use of SU in mRCC pts with lung mets should be encouraged.

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