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Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial.

Garufi C, Torsello A, Tumolo S, Ettorre GM, Zeuli M, Campanella C, Vennarecci G, Mottolese M, Sperduti I, Cognetti F - Br. J. Cancer (2010)

Bottom Line: After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day.Partial response was noticed in 34 patients (79%).Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. carlo.garufi@fastwebnet.it

ABSTRACT

Background: We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases.

Methods: This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day.

Results: Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.

Conclusion: Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.

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Related in: MedlinePlus

Kaplan–Meier curves of progression-free survival (PFS) and overall survival. (A) The PFS in the entire population (n=43); (B) PFS in resected (unbroken line) and not resected (broken line) patients. (C) Overall survival in the entire population (n=43); (D) overall survival in resected (unbroken line) and not resected (broken line) patients.
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fig3: Kaplan–Meier curves of progression-free survival (PFS) and overall survival. (A) The PFS in the entire population (n=43); (B) PFS in resected (unbroken line) and not resected (broken line) patients. (C) Overall survival in the entire population (n=43); (D) overall survival in resected (unbroken line) and not resected (broken line) patients.

Mentions: The PFS for all patients was 14 months (95% CI: 11–17 months; Figure 3). For those patients who were resected, PFS was 15 months (95% CI: 12–19 months; Figure 3), whereas PFS was 9 months (95% CI: 1–17 months) for those patients who were not resected. The median time from surgery until relapse was 11 months (95% CI: 9–13 months). After liver surgery, 10 out of 26 patients (38%) had disease recurrence in the liver, 4 out of 26 (15%) patients had disease recurrence outside the liver (one presented already extrahepatic disease at study entry) and 6 out of 26 patients (23%) had disease recurrence both in the liver and outside (none of these 6 patients presented extrahepatic disease at study entry). Median estimated OS for all patients was 37 months (95% CI: 21–53 months), with 68.2% of patients alive at 2 years in the entire population, 80.6% in resected patients and 47.1% in non-resected patients (P=0.01; Figure 3).


Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial.

Garufi C, Torsello A, Tumolo S, Ettorre GM, Zeuli M, Campanella C, Vennarecci G, Mottolese M, Sperduti I, Cognetti F - Br. J. Cancer (2010)

Kaplan–Meier curves of progression-free survival (PFS) and overall survival. (A) The PFS in the entire population (n=43); (B) PFS in resected (unbroken line) and not resected (broken line) patients. (C) Overall survival in the entire population (n=43); (D) overall survival in resected (unbroken line) and not resected (broken line) patients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990583&req=5

fig3: Kaplan–Meier curves of progression-free survival (PFS) and overall survival. (A) The PFS in the entire population (n=43); (B) PFS in resected (unbroken line) and not resected (broken line) patients. (C) Overall survival in the entire population (n=43); (D) overall survival in resected (unbroken line) and not resected (broken line) patients.
Mentions: The PFS for all patients was 14 months (95% CI: 11–17 months; Figure 3). For those patients who were resected, PFS was 15 months (95% CI: 12–19 months; Figure 3), whereas PFS was 9 months (95% CI: 1–17 months) for those patients who were not resected. The median time from surgery until relapse was 11 months (95% CI: 9–13 months). After liver surgery, 10 out of 26 patients (38%) had disease recurrence in the liver, 4 out of 26 (15%) patients had disease recurrence outside the liver (one presented already extrahepatic disease at study entry) and 6 out of 26 patients (23%) had disease recurrence both in the liver and outside (none of these 6 patients presented extrahepatic disease at study entry). Median estimated OS for all patients was 37 months (95% CI: 21–53 months), with 68.2% of patients alive at 2 years in the entire population, 80.6% in resected patients and 47.1% in non-resected patients (P=0.01; Figure 3).

Bottom Line: After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day.Partial response was noticed in 34 patients (79%).Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. carlo.garufi@fastwebnet.it

ABSTRACT

Background: We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases.

Methods: This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day.

Results: Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.

Conclusion: Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.

Show MeSH
Related in: MedlinePlus