Bevacizumab as adjuvant treatment for colon cancer: Updated results from the AVANT phase III study by the GERCOR group

Purpose The National Surgical Adjuvant Breast and Bowel Project C-08 trial was designed to investigate the safety and effectiveness of adding bevacizumab to modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen for the adjuvant treatment of patients with stage II or III colon cancer. We present safety information in advance of the planned analysis of efficacy. Patients and Methods Among 2,710 randomly assigned patients, demographic factors were balanced. Patients received modified FOLFOX6 every 2 weeks × 12 or modified FOLFOX6 plus bevacizumab (5 mg/kg every 2 weeks × 26, experimental group). Results Overall rates of grade 4 or 5 toxicities were nearly identical in the FOLFOX6 and FOLFOX6 plus bevacizumab arms (15.2% and 15.0%, respectively). Six-month mortality rates were 0.96% and 0.90% for the control and experimental groups, respectively. Grade 3+ toxicities that occurred more often in the experimental arm versus control arm included hypertension (12% v 1.8%, respectively), wound complications (abdominal incisional hernia or infusion port dehiscence/inflammation; 1.7% v 0.3%, respectively), pain (11.1% v 6.3%, respectively), and proteinuria (2.7% v 0.8%, respectively). Grade 2+ neuropathy was increased in the experimental arm versus the control arm (grade 2, 33% v 29%, respectively; grade 3, 16% v 14%, respectively; and grade 4, < 1% each). In the experimental arm versus control arm, significantly less thrombocytopenia (1.4% v 3.4%, respectively) and fewer allergic reactions (3.1% v 4.7%, respectively) were observed. Advanced age was associated with a significantly greater rate of grade 4 and 5 toxicities regardless of treatment. Conclusion Bevacizumab with modified FOLFOX6 is well tolerated in the surgical adjuvant setting in these patients. No significant increase in GI perforation, hemorrhage, arterial or venous thrombotic events, or death with the addition of bevacizumab to modified FOLFOX6 has been observed. Follow-up for potential delayed adverse effects and efficacy is ongoing.

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Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group

Annals of Oncology ◽

10.1016/j.annonc.2019.12.006 ◽

2020 ◽

Vol 31 (2) ◽

pp. 246-256 ◽

Cited By ~ 4

Author(s):

T. André ◽

D. Vernerey ◽

S.A. Im ◽

G. Bodoky ◽

R. Buzzoni ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Treatment ◽

Phase Iii ◽

Phase Iii Study

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Initial safety report of NSABP C-08, a randomized phase III study of modified 5-fluorouracil (5-FU)/leucovorin (LCV) and oxaliplatin (OX) (mFOLFOX6) with or without bevacizumab (bev) in the adjuvant treatment of patients with stage II/III colon cancer

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.4006 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 4006-4006 ◽

Cited By ~ 8

Author(s):

C. J. Allegra ◽

G. Yothers ◽

M. J. O'Connell ◽

S. Sharif ◽

N. Wolmark

Keyword(s):

Colon Cancer ◽

Adjuvant Treatment ◽

Stage Ii ◽

Phase Iii ◽

Safety Report ◽

Phase Iii Study

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Quality assurance of the 22961 EORTC trial. A phase III study of the optimal combination of hormonal adjuvant treatment by LHRH analogue and radiation therapy for the management of locally advanced prostate cancer: the dummy run

Radiotherapy and Oncology ◽

10.1016/j.radonc.2004.08.005 ◽

2004 ◽

Vol 73 (1) ◽

pp. 11-20 ◽

Cited By ~ 19

Author(s):

Vassilis E. Kouloulias ◽

Jean-Yves Giraud ◽

Bernard J. Davis ◽

Andrée Dusserre ◽

Alfredo Zurlo ◽

...

Keyword(s):

Prostate Cancer ◽

Quality Assurance ◽

Radiation Therapy ◽

Adjuvant Treatment ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Optimal Combination ◽

Phase Iii ◽

Locally Advanced Prostate Cancer ◽

Phase Iii Study

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Systemic therapy for colorectal cancer

Archive of oncology ◽

10.2298/aoo0304255s ◽

2003 ◽

Vol 11 (4) ◽

pp. 255-263 ◽

Cited By ~ 1

Author(s):

Borut Stabuc

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Metastatic Colorectal Cancer ◽

Adjuvant Treatment ◽

Randomized Clinical Trials ◽

Response Rate ◽

Phase Iii ◽

Oral Fluoropyrimidines ◽

Significant Difference

Colorectal cancer alone accounts for around 200,000 deaths in Europe and represents a significant health problem. Although about fifty percent of patients are cured by surgery alone, the other half will eventually die due to metastatic disease, which includes approximately 25% of patients who have evidence of metastases at the time of diagnosis. Surgical resection of the primary tumor and regional lymph nodes is the only curative therapy for colorectal cancer. However, adjuvant chemotherapy in stage III for colon cancer following curative resection has been shown to reduce the risk of recurrence by 19-40% and of death by 16-33%. Today, 5-fluoroUracil and Leucovorin given for six months may represent the best adjuvant treatment available The contribution of levamisole to adjuvant treatment seems to be marginal, if any. The benefit of adjuvant chemotherapy for the patients with Dukes B colon cancer is less clear. A meta-analysis of 1,381 patients with advanced colorectal cancer showed a significant increase in response rate with the bolus 5-fluoroUracil and Leucovorin versus 5-fluoroUracil alone but no significant difference in median survival. Continuous infusion allows higher doses of 5-FU than rapid bolus infusion and improves response rate survival and time to progression. Oral fluoropyrimidines (capecitabine and Uracil/Tegafur [UFT]) are as active as intravenous fluoropyrimidines. Compared to intravenous 5FU, oral fluoropyrimidines have safety advantages clinical benefits, and are more convenient for patients. Phase III randomized clinical trials in patients with metastatic colorectal cancer demonstrate the significant superiority of combining irinotecan with 5-fluoroUracil and Leucovorin or oxaliplatin with 5-fluoroUracil and Leucovorin over the same 5-fluoroUracil and Leucovorin alone. Several phase II studies have shown that the combination of the oral fluoropyrimidines plus irinotecan or oxaliplatin is very active in metastatic colorectal cancer. Trials with agents acting on novel targets in colorectal cancer are progressing rapidly, including doxifluridine, new inhibitors of thymidylate synthase (ZD9331), oral camptothecins (Rubitecan), multitarget antifolate antimetabolite (Premetrexet), inhibitors of epidermal growth factor receptor (Cetuximab), COX-2 inhibitors (celecoxib) and farnesyltransferaze inhibitors (Zarnestra). However, a few randomized trials failed to show a survival advantage compared with placebo in patients with advanced refractory colorectal cancer.

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