Effect of continuation of bevacizumab following disease progression in patients with metastatic colorectal cancer on survival

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15143-e15143
Author(s):  
G. F. Samelis ◽  
A. Tsiakou ◽  
M. Karamanidi ◽  
M. Pelechrini ◽  
A. Zaganides ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Clinical Activity ◽  
Line Treatment ◽  
First Line ◽  
Standard Chemotherapy ◽  
Multiple Line ◽  
Co Morbidity

e15143 Background: The management of patients with metastatic colorectal cancer (mCRC) has evolved dramatically over the last decade, with several “targeted” agents having entered the treatment arena. Multiple-line treatment is now considered as an important step towards the optimal therapeutic strategy for this patient population. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown clinical activity in patients with mCRC when used either as a first-line or second-line treatment. Currently, there is limited information in the literature on the use of bevacizumab combination chemotherapy in multiple lines with regimens including irinotecan and oxaliplatin, in mCRC patients who have progressed. Methods: We evaluated the efficacy and safety of bevacizumab in combination with standard chemotherapy (irinotecan, capecitabine, oxaliplatin, cetuximab) in 21 patients with metastatic colorectal cancer with a median age of 69 (range: 47–85) years old with PS: 0–1, included in the study. The metastatic sites were liver in 13 patients, liver and lung in 4 patients, lung in 2 patients, intra-abdominal in 1 patient and urinary-bladder in 1 patient. Bevacizumab treatment was continuously dispensed after disease progression and only other combined drugs were altered. Subgroup analysis was performed in terms of age, site of metastases, spread and co-morbidity. Results: The median age of the patients included in the analysis was 69 years (range 47–85). Progression free survival (PFS) was 17 months in first line setting (overall survival (OS) not reached yet) o, and for the age group >69 and <69 it was 23 and 16 months respectively (p=0.4565). Overall survival for the <69 years old was 36 months. Anemia (all grades) was reported in 90.6% of the patients, while hemorrhage and thrombosis were reported in 28.6% and 14.3% respectively. Conclusions: Multiple line treatment in advanced colorectal cancer, including bevacizumab combined with standard chemotherapy, may improve OS (median: 23+ months) with an acceptable toxicity profile in patients with mCRC. However, further research through well-designed randomized studies is warranted to appraise the beneficial risk- benefit ratio of such an approach. No significant financial relationships to disclose.

Maintenance treatment with cetuximab in a series of patients treated with standard chemotherapy and cetuximab in metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 624-624
Author(s):  
G. Quintero-Aldana ◽  
S. Varela ◽  
B. Campos ◽  
S. Vazquez-Estevez ◽  
O. Maseda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Standard Chemotherapy ◽  
Cutaneous Toxicity

624 Background: New strategies are needed to improve outcomes and reduced toxicities of currently treatments for patients with advanced colorectal cancer. Nowadays maintaining treatment until disease progression is the standard option for these patients. Cetuximab is a recombinant humanized monoclonal antibody that neutralizes epidermal growth factor receptor and it has shown benefit not only in combination with standard chemotherapy in first- and second-line treatment or as a single agent in progression to standard chemotherapy in KRAS wild-type metastatic colorectal cancer (mCRC). Methods: This data describes patients who received standard chemotherapy with cetuximab every two weeks. For patients with response or stable disease, cetuximab was continued until disease progression or unacceptable toxicity. Results: Twelve patients are reported, nine were male (75%). The median age was 62 years (range, 46 to 78 years). All patients had stage IV, and liver was the most common location (75%). The majority of patients (75%) received FOLFOX VI as a first-line treatment in combination with cetuximab; only two patients were treated with FOLFIRI. Cetuximab was maintained after the first line of treatment in the 75% of patients. The median of cycles of chemotherapy and cetuximab was 12. Best response achieved in this setting was complete response (58.3%, 7/12). Median of monotherapy with cetuximab treatment was 7.5 cycles (range 3 to 12). At the moment of this analysis seven of twelve patients continued with the maintenance. In the rest of patients the treatment was followed until progression (33%, 3/12). No grade 3-4 toxicities were seen during maintenance cetuximab. The most common adverse effect during maintenance was cutaneous toxicity but the majority of patients had minor toxicity (50% grade 1). Conclusions: Cetuximab has significant antitumor activity not only as a single agent or in combination with standard chemotherapy but may also when it is used as maintenance therapy after a complete or partial response to first or second line based chemotherapy in mCRC. Maintenance cetuximab is feasible, safe, and worthy of future study in advanced colorectal cancer. No significant financial relationships to disclose.

Effect of the addition of bevacizumab to first-line FOLFOX on efficacy, including response rate, progression-free survival, and overall survival, in patients with metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 588-588
Author(s):  
M. Suenaga ◽  
N. Mizunuma ◽  
S. Matsusaka ◽  
E. Shinozaki ◽  
M. Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Response Rate ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

588 Background: Bevacizumab (BV) is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Used in combination with chemotherapy, BV has been shown to improve survival in both first- and second-line treatment for metastatic colorectal cancer (mCRC). However, it was reported that addition of BV to FOLFOX conferred only little survival benefit (Saltz et al. JCO2008). The aim of this study was to assess the efficacy of addition of BV to FOLFOX in first-line treatment for patients with mCRC. Methods: Bevacizumab was approved for mCRC in July 2007 in Japan. This study was conducted at a single institution and comprised 217 consecutive patients receiving first-line treatment for mCRC between 2005 and 2009. The primary objective was to compare survival benefit in patients treated with FOLFOX4 (FF) between 2005 and 2007 with that in patients receiving FOLFOX4+BV 5 mg/kg (FF+BV) between 2007 and 2009. Results: Total number of patients in the FF and FF+BV groups was 132 and 85, respectively. Characteristics of patients were as follows (FF vs. FF+B): median age, 62 yrs (range 28-76 yrs) vs. 60 yrs (range16-74 yrs); ECOG PS0, 98.8% vs. 81.8%; and median follow-up time, 20.8 months vs. 24.4 months. Median progression-free survival (PFS) in the FF and FF+BV groups was 10 months (95% CI, 8.7-11.3) and 17 months (95% CI, 10.2-14.1), while median overall survival (OS) was 21 months (95% CI, 17.9-24.1) and not reached, respectively. Response rate was 46% (95% CI, 37- 54) in FF, and 62% (95% CI, 51-73) in FF+BV. Addition of BV to FOLFOX4 significantly improved PFS (p=0.002) and OS (p<0.001). Conclusions: The additive effect of BV for first-line FOLFOX was reconfirmed. These data indicate potential survival benefits from the addition of BV to FOLFOX in first-line treatment of mCRC. In addition, PFS may be a sensitive indicator of outcome prior to post-treatment. No significant financial relationships to disclose.

Addition of bevacizumab to first-line FOLFOX4 and overall survival in patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 610-610 ◽  
Author(s):  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Nobuyuki Mizunuma ◽  
Eiji Shinozaki ◽  
Mariko Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

610 Background: In our previous report, addition of bevacizumab (BV) to the FOLFOX4 regimen appeared to significantly improve response rate, progression-free survival and overall survival in first-line treatment for patients with metastatic colorectal cancer (mCRC) (Suenaga M, et al. ASCO-GI 2011 [abstr 588]). Update results met median overall survival, and statistical analysis of survival was performed. Methods: An observational cohort study was carried out on all eligible patients scheduled to receive FOLFOX4 (n = 128) or FOLFOX4+BV (n = 85) between 2005 and 2007, 2007 and 2009, with a median follow-up time of 20.4 months vs. 30.2 months, respectively. Predefined efficacy endpoints were treatment characteristics, response rates, progression-free survival, and overall survival in the periods of time observed. Results: Median progression-free survival was 9.9 months (95% CI, 8.4-11.4) in the FOLFOX4- and 17 months (95% CI, 11.8-22.3) in the FOLFOX4+BV-treated patients (p=0.002). Median overall survival times were 20.5 months (95% CI, 16.9-24) and 38.8 months (95% CI, 32.9-44.8) in the two groups, respectively (p<0.001). In the ECOG PS 0 population, progression-free survival in the FOLFOX4 and FOLFOX4+BV groups was 11 months and 17 months with a hazard ratio of 0.63 (95% CI, 0.44-0.89) in favour of FOLFOX4+BV, similarly in OS with a hazard ratio of 0.53 (95% CI, 0.36-0.77). Subgroup population received 5-FU plus leucovorin (FL) as maintenance during oxaliplatin discontinuation due to adverse events had longer PFS or OS in both groups, though no significance. PFS were 14.7 and 21.6 months, and OS were 29 and 45.9 months, respectively. Secondary resection was performed more in FOLFOX4+BV (11.8%) than FOLFOX4 (3.9%) patients. Conclusions: These data indicate potential survival benefits from the addition of BV to the FOLFOX4 regimen as first-line treatment for mCRC. Maintenance using FL after discontinuation of oxaliplatin due to adverse events appeared to be an essential factor for better survival.

scholarly journals Fluorouracil, Leucovorin, and Oxaliplatin With and Without Cetuximab in the First-Line Treatment of Metastatic Colorectal Cancer

2009 ◽  
Vol 27 (5) ◽  
pp. 663-671 ◽  
Author(s):  
Carsten Bokemeyer ◽  
Igor Bondarenko ◽  
Anatoly Makhson ◽  
Joerg T. Hartmann ◽  
Jorge Aparicio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Kras Mutation ◽  
Odds Ratio ◽  
Line Treatment ◽  
First Line ◽  
Mutation Status ◽  
Kras Mutation Status ◽  
First Line Treatment

Purpose This randomized study assessed whether the best overall response rate (ORR) of cetuximab combined with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) was superior to that of FOLFOX-4 alone as first-line treatment for metastatic colorectal cancer. The influence of KRAS mutation status was investigated. Patients and Methods Patients received cetuximab (400 mg/m2 initial dose followed by 250 mg/m2/wk thereafter) plus FOLFOX-4 (oxaliplatin 85 mg/m2 on day 1, plus leucovorin 200 mg/m2 and fluorouracil as a 400 mg/m2 bolus followed by a 600 mg/m2 infusion during 22 hours on days 1 and 2; n = 169) or FOLFOX-4 alone (n = 168). Treatment was continued until disease progression or unacceptable toxicity. KRAS mutation status was assessed in the subset of patients with assessable tumor samples (n = 233). Results The confirmed ORR for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone (46% v 36%). A statistically significant increase in the odds for a response with the addition of cetuximab to FOLFOX-4 could not be established (odds ratio = 1.52; P = .064). In patients with KRAS wild-type tumors, the addition of cetuximab to FOLFOX-4 was associated with a clinically significant increased chance of response (ORR = 61% v 37%; odds ratio = 2.54; P = .011) and a lower risk of disease progression (hazard ratio = 0.57; P = .0163) compared with FOLFOX-4 alone. Cetuximab plus FOLFOX-4 was generally well tolerated. Conclusion KRAS mutational status was shown to be a highly predictive selection criterion in relation to the treatment decision regarding the addition of cetuximab to FOLFOX-4 for previously untreated patients with metastatic colorectal cancer.

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