Phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in patients with unresectable metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 611-611 ◽  
Author(s):  
Takeshi Kato ◽  
Tomohiro Nishina ◽  
Kentaro Yamazaki ◽  
Takayuki Yoshino ◽  
Yoshinori Miyata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Regression ◽  
Performance Status ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Prolonged Treatment ◽  
Efficacy And Safety ◽  
Resection Rate ◽  
Ecog Performance Status ◽  
Grade 3

611 Background: The results from a randomized phase II trial in the first-line treatment of mCRC indicated that SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) had promising activity with well-tolerated toxicities compared to mFOLFOX6 (Ojima et al, ESMO 2011). The median progression-free survival (PFS) for SOL and mFOLFOX6 was 9.6 and 6.9 months, respectively (HR=0.83). We evaluated the efficacy and safety of adding BV to SOL regimen in this study. Methods: The inclusion criteria were; 1) histologically proven adenocarcinoma of colon or rectum, 2) age ≥ 20 years, 3) no prior treatment for metastatic disease, 4) at least one target lesion by RECIST ver1.0 criteria, 5) ECOG Performance Status 0-1. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week and L-OHP (85 mg/m2), and BV (5 mg/kg) on day 1, every 2 weeks. The primary endpoint was the response rate (RR). Results: From October 2009 to April 2010, 31 pts were enrolled, and 29 pts were regarded as the population of full analysis set. Present data included the results of efficacy and safety up to 24 cycles. RR assessed by the independent review committee was 86.2 % (CR: 0 pts, PR: 25 pts), and disease control rate (DCR) was 100%. The median PFS assessed by investigators was 12.5 months, while further follow up is ongoing. One year survival rate was 100%. The incidence of grade 3/4 adverse drug reactions were; neutropenia 16.7%, diarrhea 10.0%, hypertension 16.7%, and sensory neuropathy 53.3%. The median cumulative oxaliplatin dose was 915.0 mg/m2 (range 330-1735 mg/m2). The high prevalence of grade 3 neuropathy seemed due to the prolonged treatment duration. Reasons for discontinuation were progressive disease in 13 pts, and metastatectomy by tumor regression in 6 pts. The resection rate was 17.2 %. Conclusions: SOL+BV showed promising activity with high RR, DCR, PFS and resection rate with well tolerated toxicities in pts with unresectable mCRC. This trial was supported by Taiho Pharmaceutical CO.,LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881).

Phase II efficacy and safety study of nintedanib versus sunitinib in previously untreated renal cell carcinoma (RCC) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4506-4506 ◽  
Author(s):  
Tim Eisen ◽  
Yaroslav Shparyk ◽  
Robert Jones ◽  
Nicholas James MacLeod ◽  
Graham Temple ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Qtc Interval ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Interval Change ◽  
First Line Therapy

4506 Background: Sunitinib (S) is established as a standard first-line therapy for patients (pts) with advanced RCC. However, treatment can be limited by the occurrence of drug-related adverse events (AEs). This Phase II study assessed the efficacy and safety of nintedanib (N) – a potent, triple angiokinase inhibitor of VEGFR-1–3, PDGFR-α/β, and FGFR-1–3, as well as RET and Flt3 – vs S in previously untreated pts with RCC. Methods: Ninety-nine eligible pts (96 of whom were treated) with advanced, unresectable/recurrent clear cell RCC, an ECOG performance status of 0–1, and no prior systemic therapy were randomized 2:1 to receive N 200 mg twice daily (n=64; given in 4-week cycles) or S 50 mg once daily (n=32; 4 weeks on, 2 weeks off schedule). Treatment continued until disease progression or unacceptable drug-related AEs. Primary endpoints were progression-free survival at 9 months (PFS-9) and, in N-treated pts only, QTc interval change (baseline to day 15). Secondary endpoints included PFS, objective response rate (ORR; RECIST 1.1), overall survival (OS), time to progression (TTP), time to treatment failure (TTF), and AEs. Results: Baseline characteristics were balanced between the arms. PFS-9 was not statistically significantly different between N- and S-treated pts (43 vs 45%; p=0.85). There were also no statistically significant differences between N and S with regard to PFS (median: 8.44 vs 8.38 mo; hazard ratio: 1.16; 95% CI: 0.71–1.89; p=0.56), confirmed ORR (18.8 vs 31.3%; p=0.19), OS (median: 20.37 vs 21.22 mo; p=0.63), TTP (median: 8.48 vs 8.54 mo; p=0.52), and TTF (median: 8.41 vs 8.36 mo; p=0.46). Grade ≥3 AEs occurred in 47% of N-treated pts and 56% of S-treated pts. Common AEs (all grades; N vs S) included diarrhea (61 vs 50%), nausea (38 vs 34%), fatigue (both 25%), and vomiting (16 vs 22%). Dermatologic AEs (8 vs 47%) were less frequent with N than S. There was no increase from baseline in QTc >60 ms on days 1 or 15 in N-treated pts, and there was no relationship between N exposure and QT interval change. Conclusions: N demonstrated similar efficacy to S and had a manageable safety profile, including a lower incidence of dermatologic AEs vs S. In addition, N was not associated with QT prolongation. Clinical trial information: NCT01024920.

Efficacy and safety of oral etoposide maintenance therapy following cisplatin plus etoposide in advanced small cell lung cancers (Study of the Anatolian Society of Medical Oncology).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18546-e18546
Author(s):  
Zuhat Urakci ◽  
Muhammet Ali Kaplan ◽  
Olcun Umit Unal ◽  
Mehmet Kucukoner ◽  
Alper Sevinc ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Performance Status ◽  
Progression Free Survival ◽  
Small Cell ◽  
Oral Etoposide ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
Ecog Performance Status ◽  
Lung Cancers ◽  
Grade 3

e18546 Background: Small cell lung cancers (SCLC) constitute a mean of 15% of lung cancers and present with advanced disease at time of diagnosis in 60% of cases. Cisplatin plus etoposide schedule is the standard treatment in these patients , whereas the role of maintenance therapy is debated. We assessed the efficacy and safety of oral etoposide maintenance therapy following cisplatin plus etoposide in advanced SCLC. Methods: Demographic features, treatment response, survival rate, and toxicity rate were assessed in our patients who were followed up for advanced SCLC between 2006 and 2012, had a ECOG performance status of 0-1, and were given oral etoposide maintenance therapy (50mg/day, given 14 days of a 21-day cycle, a total of 6 cycles) following 6 courses of cisplatin (75 mg/m2, 1 day) and etoposide (100mg/m2, 3 days). Results: A total of 51 patients were studied, 46 (90.2%) of whom were male; the mean age was 59 (28-78) years at diagnosis. Forty-four (86.2%) patients had partial remission while 7 (13.7%) had complete remission. Nine (17.6%) developed neutropenic fever while grade 3-4 toxicities, neutropenia, anemia, thrombocytopenia, neuropathy, diarrhea, nausea and vomiting were present in 39.2%, 9.8%, 5.9%, 1.9%, 3.9%, 3.9%, and 1.9% respectively. Chemotherapy was postponed in fourteen (27.4%) patients due to toxicity. Six (11.7%) patients taking oral etoposide developed febrile neutropenia and 3 (5.9%) developed grade 3-4 thrombocytopenia. Chemotherapy was postponed in 5 (9.8%) patients due to toxicity while no toxic death was observed. After a median follow-up of 19 months, 32 (62.7%) patients experienced progression of disease and 29 (56.8%) died. Median progression free survival was found 11.6 months (%95 CI; 10.2-12.9 months) and median overall survival was found 15.6 (%95CI; 11.5-19.7 months) months. Conclusions: Our results were similar with the previous literature. Oral etoposide maintenance therapy following cisplatin plus etoposide therapy in advanced SCLC is effective and tolerable. Further randomized studies are needed in this topic.

Phase II study of pazopanib with weekly paclitaxel in refractory urothelial cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 294-294 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Russell Kent Pachynski ◽  
Anthony P. Lam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Upper Urinary Tract ◽  
Weekly Paclitaxel ◽  
Moderate Activity ◽  
Ecog Performance Status ◽  
Grade 3

294 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been observed in trials evaluating established chemotherapeutics as single agents or in combination regimens. Paclitaxel has moderate activity when used alone and in combination in UC. Pazopanib is active in other solid tumors secondary to its potent anti-angiogenic effects. We report the results of a multi-center phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Eligible patients (pts) had histologically confirmed UC, with disease that progressed on upto 2 chemotherapeutic regimens. Pazopanib (800 mg) was administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of the study was response-rate (RR) based on RECISTv 1.1 criteria. Secondary endpoints included safety, and progression free-survival (PFS). Results: From April 2010 to September 2014, 32 patients were enrolled. Median age was 67 years (29-89) and median ECOG performance status was 1 (0-2). 17 pts (54%) had UC of the upper urinary tract disease and 15(47%) had primary bladder tumors. All pts had multiple metastatic sites, including 9 (28%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Objective responses were observed in 58% with 3 (12%) complete responses (CR), and 12 pts (46%) with partial responses (PR). Another 9 (35%) acheived stable disease (SD). High grade toxicities included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). Nearly half of the patients( n= 14 ) required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity in relapsed/refractory UC. This combination is safe, effective and is worthy of evaluation in randomized phase 3 study. Clinical trial information: NCT01108055.

Randomized phase II study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7680-7680 ◽  
Author(s):  
T. J. Lynch ◽  
D. W. Fenton ◽  
V. Hirsh ◽  
D. J. Bodkin ◽  
E. Middleman ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Performance Status ◽  
Treatment Options ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Previously Treated ◽  
Grade 3

7680 Background: Treatment options for previously treated NSCLC are limited, warranting consideration of novel combinations. This study evaluated the activity and toxicity of erlotinib with bortezomib, a proteasome inhibitor. Dosing was based on the approved indication for erlotinib and on phase I data for the combination. Methods: Patients (pts) with Stage IIIB/IV NSCLC who progressed following one prior line of chemotherapy, with no prior exposure to an EGF-receptor inhibitor and ECOG performance status 0 or 1 were randomly assigned to erlotinib 150 mg po daily alone (arm A) or in combination with bortezomib 1.6 mg/m2 iv on days 1 and 8 (arm B) of a 21-day cycle. Response was evaluated by RECIST and toxicity was graded using NCI CTCAE 3.0. A Simon optimal two-stage design was used to evaluate anti-tumor activity in response-evaluable pts. Results: Fifty pts were treated at 17 sites (January-June 2006); baseline characteristics and treatment intensity were comparable in both arms. Among 24 response-evaluable pts in each arm, there were 3 partial responses (PR) and 1 complete response in arm A and 2 PR in arm B. Median progression-free survival (PFS) was 2.7 and 1.4 months in arms A and B, respectively. The study was halted as required at the planned interim analysis due to insufficient clinical activity in arm B. Activity and toxicity in arm A were consistent with published reports for erlotinib alone. Adverse-event profiles were as expected in both arms, with no significant additivity. In arm B, one pt died of pneumonia. The most common grade 3 treatment-related toxicity was skin rash (12% arm A and 8% arm B), and rash severity correlated with PFS: grades 2/3, 2.8 months PFS (20 pts); grades 0/1, 1.4 months PFS (28 pts), p=0.032. In arm B, one pt each had grade 3 anorexia, hypokalemia, and worsened peripheral sensory neuropathy compared with baseline. There were no grade 4 treatment related toxicities in either arm. Conclusions: The combination of erlotinib and bortezomib in the doses and schedules used in this trial was well tolerated but did not show sufficient activity at this dose and schedule to warrant further development. No significant financial relationships to disclose.

Efficacy and safety of bevacizumab (BEV)-based combination regimens in patients with metastatic colorectal cancer (mCRC): Randomized phase II study of BEV + FOLFIRI versus BEV + XELIRI (FNCLCC ACCORD 13/0503 study)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4086-4086
Author(s):  
M. Ducreux ◽  
A. Adenis ◽  
J. Mendiboure ◽  
E. François ◽  
E. Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Free Survival ◽  
First Line Therapy ◽  
Number Of Cycles ◽  
Combination Regimens

4086 Background: The combination of BEV and chemotherapy is highly effective in patients with mCRC and improves response rate, progression-free survival and overall survival compared with chemotherapy alone. This randomized non-comparative phase II trial evaluated the efficacy and safety of BEV in combination with either XELIRI or FOLFIRI as first-line therapy for mCRC. Methods: Patients were eligible for inclusion in this study if they had histologically proven measurable mCRC, were aged 18–75 years, and had an ECOG performance status (PS) of 0–2. Patients were treated with 8 cycles of XELIRI (irinotecan 200 mg/m2 on Day 1 and capecitabine 1000 mg/m2 bid on Days 1–14) + BEV 7.5 mg/kg on Day 1, every 3 weeks or 12 cycles of FOLFIRI (irinotecan 200 mg/m2 on Day 1 + 5-fluorouracil (5-FU) 400 mg/m2 + folinic acid 400 mg/m2 on day 1 followed by 5-FU 2400 mg/m2 via 46-h infusion) + BEV 5 mg/kg on day 1, every 2 weeks. BEV was continued to disease progression. Patients aged ≥65 years received a lower daily dose of capecitabine (800 mg/m2 bid). The primary endpoint was crude progression-free survival (PFS) at 6 months. Results: In total, 145 patients were entered in the study between March 2006 and January 2008; 72 patients received BEV + XELIRI and 73 patients received BEV + FOLFIRI (male 64%/48%; median age 61/61 years; 35/36% aged >65 years). Preliminary results from the first 6 months of follow-up are reported here. A total of 491/783 cycles was administered, 63%/67% receiving at least the initially planned number of cycles (8 cycles for BEV + XELIRI and 12 for BEV + FOLFIRI). Main results are given in the table . Conclusions: This randomized non-comparative study has shown that BEV + XELIRI and BEV + FOLFIRI are similarly effective treatments for patients with mCRC, with manageable toxicity profiles. Results with updated follow-up will be presented at the Meeting. [Table: see text] [Table: see text]

An update on gemcitabine, rituximab, and oxaliplatin in combination for relapsed/refractory non-Hodgkin lymphomas.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8084-8084
Author(s):  
Robert M. Crescentini ◽  
Kendra Lynn Sweet ◽  
Jijun Liu ◽  
Idalia Liboy ◽  
Samir Dalia ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Ecog Performance Status ◽  
Salvage Regimen ◽  
Bulky Disease ◽  
Grade 3 ◽  
Large B Cell

8084 Background: Relapsed/refractory non-Hodgkin lymphomas (NHL) have no standard of care. A variety of salvage chemotherapy options are available. We previously reported results of our phase II trial using gemcitabine, rituximab and oxaliplatin (GROC) in the salvage setting for relapsed/refractory NHL in which we observed an overall response rate of 58% with an incidence of grade 3-4 thrombocytopenia of 9% and neutropenic fever of 3.5%, but no grade 3-4 non-hematologic toxicities. Here we update progression free survival (PFS) and overall survival (OS) data. Methods: This phase II, single-arm, multicenter study evaluated safety and efficacy of GROC in patients with relapsed/refractory NHL. Patients were treated on a 14 day cycle. On day 1, patients with CD20+ NHL received rituximab (375 mg/m2). On day 2, patients received gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2). Granulocyte colony stimulating factor was given. Stem cell transplant (SCT) was considered after a minimum of 6 cycles. Results: A total of 58 patients were enrolled from the H. Lee Moffitt and the Auxilio Mutuo Cancer Centers. Ages ranged from 24 to 88 years (median 72 years). The majority of patients had an ECOG performance status of 0-1 (89%). Lymphoid neoplasms included large B-cell (79%), follicular (7%), lymphoblastic (1.8%), Burkitt (1.8%), primary mediastinal large B-cell (3.5%), and peripheral T-cell lymphoma (7%). Eighty-one percent of patients had stage III-IV disease, median IPI was 3, 40% had B-symptoms, 43% had bulky disease and 74% had an elevated LDH. Anthracycline-based therapy had been used in 91% of patients and 66% had received rituximab. Median PFS was 134 days (95% CI 115-153) and median OS was 296 days (95% CI 164-428). No difference in response was observed based on age >60, IPI, LDH or albumin levels. Prior therapy with rituximab (p=0.02) and initial response to front-line therapy (p=0.04) appear to correlate with improved outcomes. Nine patients went on for SCT. Conclusions: GROC is a useful salvage regimen for relapsed/refractory NHL with minimal toxicities and good clinical efficacy. Several patients were able to be successfully mobilized, collected and transplanted post GROC therapy.

Phase II trial of pazopanib and weekly paclitaxel in metastatic urothelial cancer (UC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 299-299 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Anthony P. Lam ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Ecog Performance Status ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

299 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been achieved in trials evaluating drugs as single agents or in combination regimens. Paclitaxel has activity when used alone and in combination in urothelial cancer, and pazopanib is active in solid tumors secondary to its potent anti-angiogenic effect. We report the results of an ongoing multicenter phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Patients (pts) eligible for the study have histologically confirmed UC, with relapse after receiving up to 2 chemotherapeutic regimens. Pazopanib (800 mg) is administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment is continued until disease progression or unacceptable toxicity. Primary endpoint of the study is the response-rate (RR) based on RECIST criteria. Secondary endpoints include safety, and progression free-survival (PFS). For designing the study, Simon’s two-stage method was applied, and 9 pts were recruited in the first stage. After having ≥1 response in the first group, a full enrollment of 32 pts has been initiated. Results: 25 pts were enrolled from April 2010 to September 2013. Their median age was 67 years (47-89), with a median ECOG performance status of 1 (0-2). 10 pts (40%) had UC of the upper urinary tract and 15 had primary bladder/ureter tumors. All pts had multiple metastatic sites, including 11 (44%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Based on RECIST (v1.1) criteria,13 pts (52%) had partial response (PR), 5 (20%) had stable disease (SD), and 2 (8%) had complete response (CR) (80% clinical benefit). The side effects included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). 14 pts required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity of combining paclitaxel in relapsed/refractory UC. This combination is safe, and is worthy of evaluation in larger studies. Clinical trial information: 1108055.

Phase II study of dasatinib in the treatment of head and neck squamous cell carcinoma (HNSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6022-6022 ◽  
Author(s):  
H. D. Brooks ◽  
B. Glisson ◽  
C. Lu ◽  
A. Sabichi ◽  
F. Johnson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Open Label ◽  
Ecog Performance Status ◽  
Open Label Phase ◽  
Grade 3 ◽  
Efficacy Parameters

6022 Background: Dasatinib is a potent inhibitor of src-family kinases, ephA2, PDGFR, Abl, and c-kit. A single-center, open-label, phase II trial was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of dasatinib in recurrent or metastatic HNSCC. Methods: Pts with measurable disease by RECIST, who received 0 or 1 prior regimen for recurrent or metastatic HNSCC with an ECOG performance status 0–1 and tumor tissue appropriate for IHC and FISH were eligible. Dasatinib 100 mg bid was given for 28-day cycles. Primary endpoints were 12-wk progression-free survival (PFS) and objective response rate (ORR). Pts who took at least 1 dose of dasatinib and who died or left study before 12 wks were counted as progressive disease (PD). A 2 stage design, closure after accrual of 15 pts was required if PFS was 45% or less and ORR was 0. Otherwise, planned accrual was 35. Response was assessed at 4 and 12 wks. PK was studied in pts receiving dasatinib per PEG. Biomarkers relevant to Src pathway were planned in tissue and blood. Results: Fifteen pts were accrued. To date, 13 pts are evaluable for response, and 15 pts for toxicity. No grade 3/4 hematologic toxicities were noted. Grade 2–4 nonhematologic toxicities(n): pleural effusion(2), nausea/vomiting(2), dehydration(1), diarrhea(1), dyspnea(1). Toxicity led to hospitalization of 4 pts and drug discontinuation in 5 pts. ORR was 0. One pt was stable at 12 wks (PFS: 7.6%). This pt stopped drug at 15 wks due to toxicity, but also had PD. One pt died on study and cause was deemed unlikely related. Conclusions: Dosed at 100mg bid, dasatinib led to a characteristic toxicity profile in this pt population. Rates of hospitalization and discontinuation for toxicity were fairly high. Final efficacy parameters are pending evaluation of 2 pts. Evaluation of PK and tissue/blood biomarkers is ongoing. No significant financial relationships to disclose.

A phase II study of capecitabine, irinotecan, and bevacizumab (XELIRI-A) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15019-e15019
Author(s):  
E. X. Chen ◽  
S. Welch ◽  
M. Krzyzanowska ◽  
H. MacKay ◽  
J. Knox ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Ecog Performance Status ◽  
Optimal Dosing ◽  
Open Label Phase ◽  
Dosing Strategies ◽  
Grade 3 ◽  
Ecog Ps

e15019 Background: Capecitabine (XEL), irinotecan (IRI) and bevacizumab (A) are all active agents in the treatment of mCRC. However, combining these agents has proven to be problematic due to overlapping toxicities. Optimal dosing strategies for this combination remain unclear. This study prospectively evaluated toxicity and efficacy of the XELIRI-A combination with dose modification. Methods: This was a single-institution, open-label phase II clinical trial. Eligible pts include those with previously untreated metastatic CRC, adequate organ function and ECOG performance status 0–2. IRI (200 mg / m2) and A (7.5 mg / kg) were given on day 1, and XEL (1000 mg / m2 p.o. BID) was given on days 1–14 of every 21-day cycle. The dose of XEL was reduced to 750 mg / m2 BID for pts age ≥ 65. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, time to progression, overall survival and toxicity. Results: 50 pts (ECOG PS 0:1 = 27:23; male:female= 34:16) were enrolled over 19 months. Median age was 58 (range: 35–72). 7 pts had prior adjuvant chemotherapy. A total of 360 cycles were administered, with a median of 6 (range: 1–16). To date, 20 confirmed PR, 3 unconfirmed PR, and 20 SD by RECIST criteria were observed (ORR= 40%, disease control rate 86%). The median PFS was 11.1 months (95% CI: 9.2 months - not reached), and the 1-year progression-free rate was 49%. 7 pts have gone on to have metastatectomy. The most frequently reported related grade 3 or 4 adverse events were neutropenia (6), hand-foot syndrome (6), and diarrhea (5). One death was seen on study, and 1 pt had treatment-emergent grade 3 hypertension. Conclusions: XELIRI-A at doses studied appears to be well- tolerated. Results are favorable compared to those from previous studies. XELIRI-A at reduced doses is safe and effective as first-line treatment for mCRC. [Table: see text]

Phase II study to evaluate efficacy and safety of irinotecan, capecitabine, and bevacizumab in metastatic colorectal cancer (mCRC) patients.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 501-501 ◽  
Author(s):  
Pilar Garcia Alfonso ◽  
Manuel Chaves-Conde ◽  
Andres Munoz ◽  
Antonia Salud ◽  
Carlos Garcia-Giron ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
Open Label ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Kras Status

501 Background: XELIRI regimen biweekly (combination of capecitabine and irinotecan) is an active and well tolerated treatment for mCRC. Bevacizumab provides significant clinical benefits in previously treated patients with mCRC. On this basis, the aim of this study is to evaluate the efficacy and safety of this combination. Methods: Multicentric, prospective, open-label phase II trial. Treatment scheme: irinotecan (iri) (175mg/m2 d1 q2w) + capecitabine (xel)(1,000mg/m2bid d 2-8) + bevacizumab (bev) (5mg/kg, d1 q2w). Results: 77 patients (p) were evaluated (66.2%, male) with a median age of 65.1 years (41.1-81.1). ECOG performance status was ≤1 in 96.1%. Primary tumor locations were: colon (53.2%), rectum (31.2%), and rectum/colon (15.6%). 27 p (35.1%) received adjuvant chemotherapy. Metastases were detected in liver (62.3%) and lung (54.5%). Mean time in treatment was: 7.1±4.9 months and median of cycles administered was 12(1-43). Median relative dose intensity was 89% for xel and bev and 85% for iri. Best response confirmed were: complete response (5.2%), partial response (32.5%), stable disease (46.8%). After a median of follow-up of 23.3 (0.4-39.6) months, median overall survival (OS) and progression free survival (PFS) was 24.8 and 11.8 months respectively. Analysis on Kras status was done in 71 p. There were no significant differences in OS or in PFS between WT and MUT p. 17 p (22.1%) underwent salvage surgery, 12 of whom had an R0 resection. The most frequent G3-4 toxicities were: diarrhea (18.2%), asthenia (16.9%), pulmonary embolism (13%; in eight of 10 p were asymptomatic), neutropenia (10.4%), febrile neutropenia (6.5%) and HFS (5.2%). Three treatment related deaths were reported (2 cases of multi-organ failure, and 1 case of intestinal perforation). Conclusions: Bevacizumab combined with biweekly XELIRI is an active first-line regimen for mCRC treatment with a feasible and manageable safety profile. Bevacizumab treatment efficacy was independent on Kras status. Clinical trial information: NCT00875771. [Table: see text]

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