FOLFOX-4 + cetuximab in untreated patients with advanced colorectal cancer. A phase II study of the Gruppo Oncologico dell’Italia Meridionale (prot. GOIM 2402)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3559-3559 ◽  
Author(s):  
G. Colucci ◽  
F. Giuliani ◽  
R. Mattioli ◽  
C. Garufi ◽  
R. Mallamaci ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Disease Status ◽  
First Line ◽  
Preliminary Results ◽  
Grade 3 ◽  
Line Setting ◽  
Ecog Ps

3559 Background: Cetuximab is an IgG monoclonal antibody targeting the EGFR showing to be effective both as single agent or in combination with Irinotecan (CPT-11) or Irinotecan/FU/FA in patients (pts) with EGFR-expressing metastatic colorectal cancer (CRC) in the first and second/subsequent-line setting. The current trial was designed to evaluate the efficacy and the safety of Cetuximab plus Folfox-4 as first -line treatment. The main objective was the percentage of confirmed objective response rate. Methods: Chemonaivepts with non-resectable metastatic CRC and expressing EGFR were treated with Cetuximab (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) plus Folfox-4 (every 2 weeks: Oxaliplatin 85 mg/m2, day 1; FA 100 mg/m2 2h, simultaneously with OH-P, and FU 400 mg/m2 iv bolus followed by 600 mg/m2 iv for 22h on days 1 and 2). The first evaluation of disease status (Recist criteria) was performed after the first 4 cycles and confirmed after one month. The treatment was continued until a maximum of 12 cycles of chemotherapy; the maintenaice with Cetuximab was permitted. Preliminary results: On the 65 screened pts, 47 (72%) had EGFR-expressing metastatic disease and were enrolled. Their main characteristics were: median Ecog PS 0; median age 66 yrs (range 43–74); main sites of disease: liver 31, lung 12, lymph-nodes 3, others 8. To date twenty-two pts are evaluable for activity and 27 for toxicity; 2 pts are not evaluable and 25 are too early. We observed 16 PR (72.7%), 5 NC (22.7%) and 1 PD (4.6%) for an ORR of 72.7% and a TGCR of 95.4%; the confirmed PR were 15 (68%). To date 2 pts undergone surgery of their metastases both for lung. The main adverse events grade 3/4 (NCI criteria) were: acne-like rush 18.5%, diarrea 7%, nausea/vomiting 4% and anemia 4%. Conclusions: Our preliminary results confirm that the combination of Cetuximab plus Folfox-4 has an high activity and a good safety profile in advanced CRC pts. The study is ongoing. No significant financial relationships to disclose.

First-line single-agent cetuximab in patients with advanced colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3553-3553 ◽  
Author(s):  
A. Pessino ◽  
S. Artale ◽  
A. Guglielmi ◽  
S. Sciallero ◽  
G. Fornarini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Great Majority ◽  
Skin Toxicity ◽  
Common Adverse Event ◽  
Time To Progression ◽  
Grade 3

3553 Background: The most relevant recent advance in the treatment of metastatic colorectal cancer is the fact that cure is still possible under very selected conditions. However the goal of chemotherapy remains palliative in the great majority of patients, justifying less toxic innovative approaches in so- called “window of opportunity trials”. We have pursued this idea in a phase II study of cetuximab monotherapy in chemo-naive patients with advanced colorectal cancer beyond any possibility of curative resection. Methods: Patients with non-resectable metastatic colorectal cancer (at least two metastatic sites and/or otherwise inoperable metastatic disease) were treated with cetuximab (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) until progressive disease (PD) or unacceptable toxicity. The primary end-point was objective response; secondary end-points were: stable disease, time to treatment failure and time to progression. According to Simon’s two-stage design, the number of responses/patients to stop the trial was 0/10 for stage 1 and 3/29 for stage 2. Results: Of the 44 patients screened, 42 (97%) had EGFR-expressing tumors. Thirty-nine patients (median age: 69) initiated the treatment. Two had grade 3 allergic reactions to cetuximab at the first administration leading to treatment discontinuation. The most common adverse event was skin toxicity, which occurred in 90% of the patients ( 31% grade 2, 10 % grade 3). We observed 1 complete response, 3 partial responses, 13 stable diseases (5 of which were minor responses), and 22 PD. The duration of the 4 responses were 12, 9, 9 and 6 months. Median time to progression was 2.0 months. Conclusions: The study is negative because the response rate is low. However, the duration of benefit in the few responding patients is such that it is imperative to find the molecular determinants of cetuximab activity in these cases. [Table: see text]

Phase II trial of FOLFOX6, bevacizumab and cetuximab in patients with Colorectal Cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4075-4075 ◽  
Author(s):  
A. J. Ocean ◽  
K. O’Brien ◽  
J. Lee ◽  
N. Matthews ◽  
S. Holloway ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
First Line ◽  
First Line Therapy ◽  
Primary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

4075 Background: Bevacizumab (B) + FOLFOX is widely accepted as a standard first-line therapy for metastatic colorectal cancer (mCRC). Recent treatment strategies have included the use of targeted therapies combined with chemotherapy to improve efficacy and to reduce chemotherapy-related toxicities. This Phase II study assesses first-line mFOLFOX6 + B + cetuximab (C), a monoclonal antibody approved for use in irinotecan-refractory mCRC. Methods: All pts had ECOG PS = 1, normal bone marrow, hepatic and renal function. Pts received mFOLFOX6 + B (5mg/kg) biweekly and C weekly (initially at 400 mg/m2, then subsequent doses at 250 mg/m2). Tumor assessment by imaging was done every 8 weeks. Primary endpoints are response rate, progression free-survival (PFS), overall survival (OS), and safety. The regimen would be considered promising if there were = 32 responses, or if = 60% of pts were progression-free for at least 8 months. Results: 67 pts (37 males, 30 females) were enrolled from 12/04–11/06. Median age was 57. Toxicities included Grade 4: neutropenia (6%), thrombosis/embolism (5%). Grade 3: neutropenia (13%), rash (13%), fatigue (11%), diarrhea (11%), abdominal pain (6%), neuropathy (5%), infection with ≤ Grade 2 ANC (4.5%). There were 2 deaths, 1 due to neutropenia and diarrhea and 1 to pulmonary fibrosis. As of 12/06, 9 pts were too early to evaluate. Of the remaining 58 pts, there were 32 responses (55%; 95% CI: 42%, 68%), including 3 CRs and 29 PRs; Median PFS was 9.6 months (95% CI: 8.8, 13.9 months), 71% were progression-free for at least 8 months, and median OS was not reached after a median follow-up of 11.4 months (range 1.5–25.2 months). Conclusions: Treatment with mFOLFOX6+ B + C met the pre-specified criteria for objective response and PFS to be considered promising. This regimen is associated with an acceptable toxicity profile and merits further evaluation. Supported by N01-CA-62204. No significant financial relationships to disclose.

Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous NSCLC.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7512-7512
Author(s):  
Suresh S. Ramalingam ◽  
Mikhail Shtivelband ◽  
Ross A. Soo ◽  
Carlos H. Barrios ◽  
Anatoly Makhson ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
And Gender ◽  
Ecog Ps

7512 Background: Linifanib is a potent and selective inhibitor of VEGF and PDGF receptors with modest single-agent activity in NSCLC. We evaluated the combination of linifanib with carboplatin (C) and paclitaxel (P) for first-line therapy of advanced non-squamous NSCLC. Methods: Patients (pts) with stage IIIB/IV, non-squamous NSCLC, stratified by ECOG PS and gender, were randomized to receive up to six 3-wk cycles of C (AUC 6 mg/ml/min) and P (200 mg/m2) with daily placebo (Arm A), linifanib 7.5 mg (Arm B), or linifanib 12.5 mg (Arm C). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), 12 m survival rate, and objective response rate (ORR). Safety was assessed by NCI-CTCAE v3.0. Results: 138 pts were randomized at 37 sites in 6 countries. Baseline characteristics were: median age, 61 y; men, 57%; smoker, 84%. Efficacy results are shown in the table. Thrombocytopenia was the only Grade 3/4 AE significantly higher on linifanib (Arm B: 16.7%; Arm C: 29.8%) vs. placebo (2.1%). Other adverse events (AEs) related to the dose of linifanib were diarrhea, thrombocytopenia, hypertension, weight loss, palmar-plantar erythrodysaesthesia syndrome, and hypothyroidism. Analysis of samples for predictive biomarkers including serum VEGF and placental growth factor are underway. Conclusions: The addition of linifanib to chemotherapy was tolerable at the doses tested and resulted in a significant improvement in PFS, with a modest survival improvement for Arm C in first-line therapy of advanced non-squamous NSCLC. [Table: see text]

Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

Capecitabine As First-Line Treatment for Patients Older Than 70 Years With Metastatic Colorectal Cancer: An Oncopaz Cooperative Group Study

2005 ◽  
Vol 23 (13) ◽  
pp. 3104-3111 ◽  
Author(s):  
Jaime Feliu ◽  
Pilar Escudero ◽  
Ferrán Llosa ◽  
Matilde Bolaños ◽  
Jose-Manuel Vicent ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Combination Chemotherapy ◽  
Clinical Benefit ◽  
Overall Response Rate ◽  
Advanced Colorectal Cancer ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Clinical Benefit Response ◽  
Grade 3

Purpose To determine the tolerability of capecitabine in elderly patients with advanced colorectal cancer (CRC). Patients and Methods Fifty-one patients with advanced CRC who were ≥ 70 years and considered ineligible for combination chemotherapy received oral capecitabine 1,250 mg/m2 twice daily on days 1 to 14 every 3 weeks. Patients with a creatinine clearance of 30 to 50 mL/min received a dose of 950 mg/m2 twice daily. Results A total of 248 cycles of capecitabine were administered (median, five cycles; range, one to eight cycles). The overall response rate was 24% (95% CI, 15% to 41%), including two complete responses (CR; 4%) and 10 partial responses (PR; 20%). Disease control (CR + PR + stable disease) was achieved in 67% of patients. The median times to disease progression and overall survival were 7 months (95% CI, 6.4 to 9.5 months) and 11 months (95% CI, 8.6 to 13.3 months), respectively. Of the 35 patients evaluated for clinical benefit response, 14 (40%; 95% CI, 24% to 58%) showed clinical benefit. Capecitabine was well tolerated. Treatment-related grade 3 and 4 adverse events were observed in only six patients (12%), and the most common events were diarrhea, hand-foot syndrome, and thrombocytopenia. One patient (2%) had an episode of angina, but no treatment-related deaths were reported. Conclusion Our findings suggest that capecitabine is effective and well tolerated in elderly patients with advanced CRC who are considered ineligible for combination chemotherapy.

Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy.

1997 ◽  
Vol 15 (1) ◽  
pp. 251-260 ◽  
Author(s):  
P Rougier ◽  
R Bugat ◽  
J Y Douillard ◽  
S Culine ◽  
E Suc ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
World Health ◽  
Who Grade ◽  
Pretreated Patients ◽  
Grade 3

PURPOSE To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients. PATIENTS AND METHODS Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function. RESULTS Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern. CONCLUSION CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.

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