Multicenter Phase II Study to Evaluate a 28-Day Regimen of Oral Fluorouracil Plus Eniluracil in the Treatment of Patients With Previously Untreated Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (15) ◽  
pp. 2894-2901 ◽  
Author(s):  
Sridhar Mani ◽  
Howard Hochster ◽  
Thomas Beck ◽  
Eric M. Chevlen ◽  
Mark A. O’Rourke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Dose Group ◽  
Response Rate ◽  
Phase Ii Study ◽  
Dose Ratio ◽  
Home Based ◽  
Grade 3

PURPOSE: To determine the efficacy of fluorouracil (5-FU) plus eniluracil when administered to patients with previously untreated metastatic colorectal cancer. PATIENTS AND METHODS: In this single-arm phase II study, patients with previously untreated metastatic colorectal cancer received oral eniluracil plus 5-FU (10:1 dose ratio), at 5-FU doses of 1.00 mg/m2 or 1.15 mg/m2 twice daily (every 12 hours) for 28 consecutive days repeated every 5 weeks (one cycle). Treatment continued until there was documented disease progression or unacceptable toxicity. RESULTS: Thirty and 25 patients were enrolled at a starting dose of 1.00 mg/m2 and 1.15 mg/m2, respectively. Fourteen (25%) of 55 patients (95% confidence interval, 15% to 39%) had a partial response, and 20 patients (36%) had stable disease. The median durations of the partial responses and stable disease were 23.9 weeks (range, 12.3 to 52.1+ weeks) and 24.1 weeks (range, 17.1 to 55.6+ weeks), respectively. The median durations of progression-free and overall survival were 22.6 weeks (range, 21.0 to 29.0 weeks) and 59 weeks (range, 4 to 84+ weeks), respectively. The response rate in the 1.15 mg/m2–dose group was similar to the 1.00 mg/m2–dose group (28% v 23%, respectively). Severe (grade 3/4) nonhematologic treatment-related toxicity included diarrhea (nine patients), nausea/vomiting (one patient each), mucositis (two patients), and anorexia (one patient). Severe hematologic toxicities were rare. At the 1.15 mg/m2–dose level, two patients exhibited grade 3 granulocytopenia, and two patients had grade 3 anemia. CONCLUSION: The response rate with oral 5-FU plus eniluracil is comparable with that observed with infusional 5-FU or bolus 5-FU and leucovorin. The toxicity profile of this oral regimen is acceptable for use in an outpatient home-based setting.

Multicenter Phase II Study of Bimonthly High-Dose Leucovorin, Fluorouracil Infusion, and Oxaliplatin for Metastatic Colorectal Cancer Resistant to the Same Leucovorin and Fluorouracil Regimen

1999 ◽  
Vol 17 (11) ◽  
pp. 3560-3568 ◽  
Author(s):  
Thierry André ◽  
Mohamed A. Bensmaine ◽  
Christophe Louvet ◽  
Eric François ◽  
Virginie Lucas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
High Dose ◽  
Median Response ◽  
Grade 3

PURPOSE: To evaluate the objective tumor response rates and toxicities of leucovorin (LV) plus fluorouracil (5-FU) cancer regimen combined with oxaliplatin (85 mg/m2) every 2 weeks on metastatic colorectal cancer patients with documented proof of progression while on bimonthly LV and 5-FU alone. PATIENTS AND METHODS: One hundred patients were enrolled onto this study and 97 received the study drugs between October 1995 and December 1996. Eighty-nine patients were eligible for per-protocol efficacy analysis with documented proof of progression on one of the following two treatments: LV 500 mg/m2 and continuous 5-FU infusion 1.5 to 2 g/m2/22 hours, days 1 through 2 every 2 weeks (FOLFUHD); or LV 200 mg/m2, bolus 5-FU 400 mg/m2, and continuous 5-FU infusion 600 mg/m2/22 hours, days 1 through 2 every 2 weeks (LV5FU2). In our study, 40 patients received FOLFUHD + 85 mg/m2 of oxaliplatin day 1 (FOLFOX3) and 57 patients received LV5FU2 + 85 mg/m2 of oxaliplatin day 1 (FOLFOX4). RESULTS: Of the 97 patients treated, 20 partial responses were observed (FOLFOX3/4: response rate, 20.6%; 95% confidence interval, 13% to 31.1%; FOLFOX3: response rate,18.4%; FOLFOX4: response rate, 23.5%). For patients treated with FOLFOX3/4, the median response duration for was 7.5 months, and the major toxicities were peripheral neuropathy and neutropenia. The incidence of grade 3 (National Cancer Institute common toxicity criteria) peripheral neuropathy was 20.6%; whereas the overall incidence of grade 3 to 4 neutropenia was 27.8%, 15%, and 36.9% for FOLFOX3/4, FOLFOX3, and FOLFOX4, respectively (P = .02). From the start of treatment, median progression-free survival was 4.7, 4.6, and 5.1 months for FOLFOX3/4, FOLFOX3, FOLFOX4, respectively, and median overall survival was 10.8, 10.6, and 11.1 months, respectively. CONCLUSION: This phase II study of oxaliplatin at 85 mg/m2 in combination with bimonthly LV plus 5-FU in patients with colorectal cancer resistant to LV plus 5-FU alone confirms the enhanced antitumor activity of oxaliplatin in combination with 5-FU.

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.

Phase II study of PX-866 in recurrent glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2053-2053 ◽  
Author(s):  
Marshall W. Pitz ◽  
Elizabeth A. Eisenhauer ◽  
Mary Valeria MacNeil ◽  
Brian Thiessen ◽  
David R. Macdonald ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Pik3ca Mutations ◽  
Overall Response ◽  
Grade 3

2053 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: A multinomial design of response and early progression (< 8 weeks on study) was used. In stage 1 (15 pts), 0 responses and ≥ 10 early progressions would stop accrual; after full accrual, ≥ 4 responses OR ≤ 13 early progressions was prespecified as of interest. Pts with histologically confirmed GBM, at first recurrence after chemoradiation and adjuvant temozolomide were given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam were done every cycle (8 weeks). Tumour tissue was collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRviii, PIK3CA mutations). Results: A total of 33 pts were enrolled, eligible and evaluable. Median age was 56 (range 35-78), 12 were female; 29 had performance status (PS) 0-1 and 4 had PS 2. Median time from initial diagnosis to enrolment was 308 days (range 141-1256). Median number of cycles was 1 (range 1-7). Thirty-two pts have discontinued therapy, 26 due to disease/symptomatic progression and 6 due to toxicity (5 LFT elevation and 1 allergic reaction). Other adverse effects (AE): fatigue (16 pts/2 grade 3), diarrhea (11 pts/5 grade 3), nausea (19 pts/1 grade 3), vomiting (11 pts/1 grade 3) and lymphopenia (29 pts/7 grade 3/4). Five pts had related serious AEs (1 LFTs, 1 GI and 3 venous thromboembolism) All pts were evaluable for response; 25 had a best response of progression, 1 had partial response (overall response rate 3%) and seven (21%) had stable disease (SD, median 7.3 months; range 3.1-13.6). Six month PFS was 17%. In preliminary analyses, no statistical association was found between SD and PTEN or EGFRviii status (results pending in 16 pts). Conclusions: PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of pts obtained durable stable disease. Further correlative work is required to identify the predictor of this effect. Clinical trial information: NCT01259869.

A phase II study of apatinib combined with S-1 in previously treated refractory metastatic colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15016-e15016
Author(s):  
Ning Li ◽  
Wenying Deng ◽  
Guifang Zhang ◽  
Yanwei Guo ◽  
Yijie Ma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Time ◽  
Response Rate ◽  
Phase Ii Study ◽  
Line Treatment ◽  
Third Line ◽  
Grade 3 ◽  
Third Line Treatment

e15016 Background: Although regorafenib and fruquintinib have been recommended as the third-line treatment for patients with refractory metastatic colorectal cancer (mCRC), the median survival time of mCRC is still only for 4-8 months and the low response rate and unpleasant side effects limit their use in Chinese patients. Apatinib, an oral VEGFR-2 inhibitor, has been approved as a third line treatment in metastatic gastric cancer. In addition, apatinib has demonstrated good safety, tolerability, and efficacy in the treatment of advanced solid tumors. The aim of this study was to assess the efficacy and safety of apatinib combined with S-1 in the treatment of refractory mCRC. Methods: In this prospective, open-label, single-arm, multicenter, phase II study, patients after failure of second-line chemotherapy were enrolled and took apatinib (250mg, daily) combined with S-1 (standard dose). The primary endpoint was progression free survival (PFS) and the second endpoint was response rate and overall survival time. Results: From December 2017, 22 patients (14 male) with a median age of 56y (range: 34-71 y) were enrolled and eligible for evaluation of the PFS, response rate and safety. The median PFS was 105d (95% CI: 79.01-130.98). two patients (9%) achieved partial response, 15 (68.18%) achieved stable disease, and 5 (22.72%) were progressive disease. The objective response rate and the disease control rate were 9% and 77.27%, respectively. Median overall survival was not reached. The common adverse effects were abnormal liver function (7/22; 31.81%), leukopenia (5/22; 22.72%) and thrombocytopenia (4/22; 18.18%). The incidence for grade 3-4 side effect was very low. One patient experienced grade 3 proteinuria and there were no toxic deaths. Conclusions: This preliminary result indicated that apatinib combined with S-1 may extend the PFS in mCRC, with well-tolerated toxicities, making it a promising therapeutic target for mCRC treatment. Clinical trial information: NCT03397199 .

Phase II study of S-1 plus leucovorin (a new 1-week treatment regimen followed by a 1-week rest period) in patients with untreated metastatic colorectal cancer in Japan and China.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 598-598 ◽  
Author(s):  
Tadamichi Denda ◽  
Jin Li ◽  
Ruihua Xu ◽  
Jianming Xu ◽  
Koji Ikejiri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Treatment Regimen ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Rest Period ◽  
Progression Free Survival ◽  
Grade 3 ◽  
Japan And China

598 Background: The previous phase II study of the oral S-1 plus oral Leucovorin (LV) (2 weeks’ treatment regimen followed by a 2 week rest period) for patients (pts) with untreated metastatic colorectal cancer (mCRC) have shown to be effective, but the grade 3 toxicities (diarrhea, stomatitis, and anorexia) were observed with relatively high frequency. In this phase II study, we tried to improve the administration schedule of S-1 plus LV regimens for well-tolerated toxicities and evaluated the efficacy. Methods: Pts were eligible as follows: histologically confirmed adenocarcinoma, age≥20, ECOG PS 0-1, no prior chemotherapy, at least one measurable lesion by RECIST ver1.0 criteria, adequate organ function, and written informed consent. S-1 (40-60 mg bid) and LV (25 mg bid) were orally administered for 1 week, followed by an 1 week rest period. Treatment was repeated until the onset of disease progression or unacceptable adverse events occurred. The primary endpoint was the response rate (RR), and the secondary endpoints were efficacy and safety. Results: From October 2008 to June 2009, 73 pts were enrolled in Japan and China. Of the eligible 71 pts, median age was 60 (range 27-84), Male/Female was 38/33, PS:0/1 was 39/32, and Japan/China was 32/39. RR as primary endpoint was 53.5% (95% CI, 41.3-65.5), and Disease Control Rate was 83.1%. With a median follow-up period of 26.4 months, the median Progression Free Survival was 6.5 months. Median Overall Survival was 24.3 months with the survival rate of 77.5 % at 1 year and 53.2 % at 2 years. The incidences of grade 3 adverse drug reactions were diarrhea 8.3 %, stomatitis 8.3%, anorexia 2.8%, neutropenia 9.7%, and there was no treatment-related death. Conclusions: The newly improved 1 week S-1 plus LV treatment regimen showed good efficacy and better tolerability than the 2 weeks’ treatment regimen. This therapy showed promising activity in pts with untreated mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs. This trial was supported by Taiho Pharmaceutical CO., LTD. ClinicalTrials.gov Identifier: NCT00891332 .

Multicenter phase Ib/II study of everolimus (RAD001) and tivozanib (AV-951) in patients with refractory, metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
Brian M. Wolpin ◽  
Kimmie Ng ◽  
Andrew X. Zhu ◽  
Thomas Adam Abrams ◽  
Peter C. Enzinger ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Once Daily ◽  
Phase Ib ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Ecog Ps

560 Background: Everolimus (E) is an oral inhibitor of mTOR. Tivozanib (T) is a highly potent, selective, oral inhibitor of VEGF receptors-1, -2, and -3. Preclinical data suggest antitumor activity for this combination in colorectal cancer. We therefore performed a multicenter Phase Ib trial of E + T in patients (pts) with any refractory gastrointestinal (GI) malignancy, followed by a Phase II trial of E + T in pts with refractory, metastatic colorectal cancer (mCRC). Methods: Eligibility criteria: histologically confirmed, measurable disease; ECOG PS≤2; blood pressure ≤150/100; no venous thromboembolism within prior 6 months. Pts with mCRC must have received prior fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab and anti-EGFR antibody (if KRAS wt). E was administered once daily continuously. T was administered once daily for 3 out of every 4 weeks. The Phase Ib study in pts with any GI malignancy followed a standard 3+3 design with 3 dose levels: (1) E 5 mg/d + T 1 mg/d; (2) E 10 mg/d + T 1 mg/d; (3) E 10 mg/d + T 1.5 mg/d. The Phase II study in pts with mCRC was a non-randomized, one-stage design with a primary endpoint of progression-free survival. Results: Between 02/10-12/10, 12 pts were enrolled to the Phase Ib study. Median age, 60 (39-81) years; male, 50%; ECOG PS 0/1/2, 42/58/0%; tumor types: esophagus 1, colorectal 11 pts. Dose limiting toxicities of grade 3 fatigue and grade 3 fatigue/ dehydration occurred in 2/6 pts on dose level 3. Grade 3/4 treatment-related adverse events in ≥10% of pts were dehydration, fatigue, headache, hyperglycemia, hypertension, and hypophosphatemia. The phase II study proceeded at the maximally tolerated dose (MTD) of E 10 mg/d and T 1 mg/d. Between 02/11-06/11, 40 pts with mCRC were enrolled to the phase II study. All but 1 pt received prior bevacizumab. Median age, 56 (35-81) years; male, 48%; ECOG PS 0/1/2, 45/53/2%. Treatment is ongoing. Conclusions: Among pts with refractory GI malignancies, the combination of Everolimus + Tivozanib was well-tolerated with MTD of E 10 mg/d and T 1 mg/d. A phase II trial has completed enrollment using these doses of E + T in pts with refractory mCRC; safety and efficacy data will be available for presentation.

Phase II Trial of Intravenous CI-1042 in Patients With Metastatic Colorectal Cancer

2003 ◽  
Vol 21 (8) ◽  
pp. 1498-1504 ◽  
Author(s):  
Oday Hamid ◽  
Mary L. Varterasian ◽  
Scott Wadler ◽  
J. Randolph Hecht ◽  
Al Benson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Neutralizing Antibody ◽  
Open Label ◽  
Viral Particles ◽  
Nausea And Emesis

Purpose: To evaluate the antitumor activity, safety, immune response, and replication of CI-1042 (ONYX-015), an E1B 55-kd gene-deleted replication-selective adenovirus, administered intravenously to patients with metastatic colorectal cancer Patients and Methods: Eighteen patients with metastatic colorectal cancer for whom prior chemotherapy failed were enrolled onto an open-label, multicenter, phase II study. CI-1042 was administered intravenously at a dose of 2 × 1012 viral particles every 2 weeks. Patients were evaluated for tumor response and toxicity; in addition, blood samples were taken for adenovirus DNA and neutralizing antibody analysis. Results: Common toxicities included flu-like symptoms, nausea, and emesis. All 18 patients eventually were removed from study because of progressive disease. Seven patients were assessed as having stable disease after 2 months of treatment, whereas two patients were considered to have stable disease after 4 months. Detectable circulating CI-1042 DNA was identified in 36% of patients 72 hours after last infusion, which is suggestive of ongoing viral replication. Conclusion: In this phase II study, intravenous CI-1042 was administered safely to patients with advanced colorectal cancer. Toxicity was manageable, consisting primarily of flu-like symptoms. Stable disease was experienced by seven patients for 11 to 18 weeks.

Phase II study of first-line combined chemotherapy bevacizumab with modified RPMI regimen for elderly or frail patients with unresectable or metastatic colorectal cancer (OGSG0802).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 573-573
Author(s):  
Shigeyoshi Iwamoto ◽  
Takeshi Kato ◽  
Motoki Yoshida ◽  
Yasuhiro Miyake ◽  
Masato Nakamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Combined Chemotherapy ◽  
First Line ◽  
Port Placement ◽  
Frail Patients ◽  
Grade 3

573 Background: The first-line combined chemotherapy RPMI regimen with bevacizumab (Bmab) in AVF2192g trial for elderly or frail patients (Pts) could be active to progression free survival (PFS), the secondary endpoint, although it may not prolong overall survival (OS), the primary endpoint. According to the results of efficacy and safety studies, a fluoropyrimidine (FU) + Bmab regimen is regarded as an option for 1st-line chemotherapy. We planned a phase II study of modified RPMI regimen with Bmab for elderly or frail Pts. Methods: Pts with confirmed unresectable/metastatic colorectal cancer without previous chemotherapy, and not suitable for intensive chemotherapy were enrolled. Pts received modified RPMI regimen (5-FU 600 mg/m2 and l-leucovorin 200 mg/m2 bolus day 1, 8, 15) and Bmab 5 mg/kg day 1, 15, q4w) until disease progression or study withdrawal. The primary endpoint was overall response rate (ORR), and the secondary endpoints were PFS, OS and safety. Results: 41 Pts were enrolled from 13 institutions. Pts characteristics were; median age 76 (range 56-90); male/female, 18/23; ECOG performance status 0/1/2, 21/19/1. The ORR, the rate of best response, the disease control rate (CR+PR+SD) were 36.6%, 56.1%, 85.4%, respectively. Median follow-up period was 14.4 months. 28 Pts (68%) had objective progression and a patient (2.4%) died without progression. The median PFS and OS were 9.0 months (95%CI, 7.5–19.6) and 24.0 months (95%CI, 20.1–NR). The incidences of grade 3 or 4 adverse events were: leukopenia (7%), neutropenia (24%), thrombocytopenia (2%), diarrhea (5%), anorexia (10%), fatigue (5%), stomatitis (7%) and hypertension (5%). Grade 3 febrile neutropenia and grade 4 pulmonary embolism was observed in one pt. Five pts (12%) discontinued the treatment due to severe or uncontrollable adverse event. Conclusions: The modified RPMI regimen with Bmab showed activity, and was well tolerated for elderly or frail Pts. ORR and the median PFS of this regimen were similar to historical data with FU + Bmab. This regimen may be a good option for not requiring percutaneous port placement Pts. Clinical trial information: UMIN000002182.

Phase II study of first-line combined chemotherapy bevacizumab with modified RPMI regimen for elderly or frail patients with unresectable or metastatic colorectal cancer (OGSG0802) update analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14601-e14601
Author(s):  
Taroh Satoh ◽  
Takeshi Kato ◽  
Motoki Yoshida ◽  
Yasuhiro Miyake ◽  
Shigeyoshi Iwamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Combined Chemotherapy ◽  
First Line ◽  
Port Placement ◽  
Oral Agents ◽  
Grade 3

e14601 Background: The first-line combined chemotherapy RPMI regimen with bevacizumab (Bmab) in AVF2192g tri al were active. According to the results of efficacy and safety, a fluoropyrimidine (FU) + Bmab regimen is regarded as one of treatment options for 1st-line chemotherapy in many guidelines. We planned a phase II study of modified RPMI regimen with Bmab especially for elderly or frail Pts. Methods: Pts with confirmed unresectable/metastatic colorectal cancer without previous chemotherapy, and not suitable for intensive chemotherapy were enrolled. Pts received modified RPMI regimen (5-FU 600 mg/m2 and l-leucovorin 200 mg/m2 bolus day 1, 8, 15) and Bmab 5 mg/kg day 1, 15, q4w) until disease progression or study withdrawal. The primary endpoint was overall response rate (ORR), and the secondary endpoints were PFS, OS and safety. Results: 41 Pts were enrolled from 13 institutions. Pts characteristics were as follows; median age 76 (range 56-90); male/female, 18/23; ECOG performance status 0/1/2, 21/19/1. The ORR, the rate of best response, the disease control rate (CR+PR+SD) were 36.6%, 56.1%, 85.4%, respectively. Median follow-up period was 14.4 months(Updated results will be presented). 28 Pts (68%) had objective progression and a patient (2.4%) died without progression. The median PFS and OS were 9.0 months (95%CI, 7.5–19.6) and 24.0 months (95%CI, 20.1–NR). The incidences of grade 3 or 4 adverse events were: leukopenia (7%), neutropenia (24%), thrombocytopenia (2%), diarrhea (5%), anorexia (10%), fatigue (5%), stomatitis (7%) and hypertension (5%). Grade 3 febrile neutropenia and grade 4 pulmonary embolism was observed in one pt. Five pts (12%) discontinued the treatment due to severe or uncontrollable adverse event. Conclusions: The modified RPMI regimen with Bmab showed promising activity, and was well tolerated for elderly or frail Pts. ORR and the median PFS of this regimen were similar to historical data with FU + Bmab. This regimen may be a good option for patients with poor PS or elderly with advantages of not requiring percutaneous port placement nor compliance or oral agents. Clinical trial information: UMIN000002182.

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