FOLFIRI Group Research Articles

546P - Tumour Shrinkage and Response Outcomes During Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment

ABSTRACT Aim: Tumour shrinkage/response are important outcomes for patients (pts) with metastatic colorectal cancer (mCRC) as they may delay progression and ultimately improve survival. Here we report tumour response data for pts with RAS WT mCRC treated with FOLFIRI ± pmab. Methods: 181 was a phase 3 randomised study of second-line pmab + FOLFIRI vs FOLFIRI alone in pts with previously treated mCRC. KRAS exon 2 wild-type (WT) samples from this study were tested for mutations in KRAS exons 3/4 and NRAS exons 2/3/4 via bidirectional Sanger sequencing and WAVE-based SURVEYOR® to identify pts with RAS WT tumours (no mutations in KRAS/NRAS exons 2, 3 or 4). Objective response rates (ORRs) and median duration of response (DoR) were calculated by treatment. Median progression-free survival (PFS) was calculated for patients with/without ≥30% tumour shrinkage at week (wk) 8. Results: Overall, 421 pts had RAS WT mCRC. Of these, 411 pts were included in the ORR analysis and 359 had tumour shrinkage data available at baseline and wk 8. More pts in the pmab + FOLFIRI vs FOLFIRI group had ≥30% tumour shrinkage at wk 8 (difference: 30% [95% confidence intervals {CI}: 22-38%]; Table). ORRs were also higher for pmab + FOLFIRI vs FOLFIRI (41% [n = 83] vs 10% [n = 21]; difference 30% [95% CI: 23-38%]). Median DoR was 7.7 vs 9.3 months for pmab + FOLFIRI vs FOLFIRI (hazard ratio [HR]: 1.02 [95% CI: 0.50-2.07]). ≥30% tumour shrinkage at wk 8 correlated with longer median PFS in both treatment groups vs Wk 8 tumour shrinkage, % ≥30 Pmab + FOLFIRI FOLFIRI Pmab + FOLFIRI FOLFIRI N (%) 114 (63) 168 (93) 67 (37) 12 (7) Median PFS, months 6.9 5.5 8.6 8.0 Conclusions: Early tumour shrinkage appears to be correlated with improved PFS in second-line mCRC. More pts with RAS WT tumours achieved ≥30% tumour shrinkage at wk 8 with pmab + FOLFIRI vs FOLFIRI alone. Disclosure: M. Peeters: Consultant/advisory roles for Amgen (all compensated) and has also received honoraria and research funding from Amgen; T.J. Price: Member of advisory boards for Amgen, Roche and Merck Serono (uncompensated); A. Sobrero: Member of advisory boards and speaker at satellite symposia fora, Merck, Roche, and Amgen; M.P. Ducreux: Member of advisory boards for Amgen, Merck, Roche, participation in symposium for Amgen, Merck, Roche; T. Andre: Advisory board membership and honoraria from Amgen; C.J.A. Punt: Amgen advisory board member; R. Koukakis: Amgen Ltd employee and stockholder; J. Terwey: Amgen (Europe) GmbH employee and stockholder; E. van Custem: EVC has received research funding from Amgen (paid to University). All other authors have declared no conflicts of interest.

Pretreatment selection of regimen according to genetic analysis improves the efficacy of chemotherapy in the first line treatment of metastatic colorectal cancer

Metastatic colon cancer patients are treated with the chemotherapy regimens, FOLFOX and FOLFIRI, in either order. So far, we cannot predict the response of chemotherapeutic agent, so it is necessary to find which regimen is adequate before starting chemotherapy. Enrolled patients are randomized into either conventional treatment or planned treatment preceded by pretreatment genetic analysis. Blood samples of patients in planned treatment group (N = 53) were analyzed for the genetic polymorphism before selection of chemotherapeutic agents. Target genes were XPD-751, GSTP-1-105, XRCC1-399 for oxaliplatin, UGT1A1 for irinotecan. The response was measured by computed tomographic scan after completion of three cycles of chemotherapy. Overall response rate was significantly higher in planned group (67.9% vs. 46.3%, P = 0.020). In FOLFOX group, response rate was significantly improved in the planned patients(77.1% vs. 50%, P = 0.018). In FOLFIRI group, the difference didn't reach statistical significance (50% vs. 42.5%, P = 0.776). We found significantly improved response rates in the chemotherapy of metastatic colon cancer by pretreatment genetic analysis, especially in FOLFOX group.

Thrombotic events in metastatic colorectal cancer patients treated with FOLFIRI plus bevacizumab.

e14630 Background: To determine the incidence and risk factors for thrombotic events (TEs) (arterial and venous) in patients with metastatic colorectal cancer (mCRC) who received Bevacizumab and FOLFIRI (Leucovorin, Fluorouracil and Irinotican ) compared to FOLFIRI alone. Methods: Single institution retrospective study of 450 mCRC patients who received either Bevacizumab plus FOLFIRI or FOLFIRI alone between October 2006 and September 2012. Demographics , TE risk factors and treatment data were abstracted from patients records. Multivariate analysis was used to determine factors that contributed to increased TE incidence. Results: 261 mCRC patients received Bevacizumab plus FOLFIRI ( 64.8 % males , mean Body Mass Index (BMI) 26.1 ) compared to 189 control patients who received FOLFIRI alone ( 61.1 % males ,BMI 27). The incidence of TEs was 15 % (arterial 1.8% + venous 13.2%) in the Bevacizumab plus FOLFIRI group compared to 15.8% (arterial 2.1% + venous 13.7%) in the control groups. Multivariate analysis controlled for age, BMI, gender, malignancy, metastatic sites , line of treatment, and risk factors did not suggest a significant increase in risk of TE associated with Bevacizumab (OR=0.83 95% CI: 0.40 - 1.70; p=0.602). No difference in locations of TEs was observed between both groups . The only statistically significant factor for thrombosis in Bevacizumab group was increased BMI (OR=1.05; 95% CI: 1.01- 1.10; p=0.016). Conclusions: Our data suggest that bevacizumab did not significantly increase the rate of thrombosis in patients with mCRC when added to FOLFIRI. To our knowledge this is the first study reporting the rate of TEs (arterial and venous) in this population.Our data suggest that BMI may be a risk factor for increase risk of thrombosis in patients treated with bevacizumab . Clinician should consider risk factors assessment prior to initiating bevacizumab .

Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer.

Background:The updated randomised phase 2/3 FIRIS study demonstrated the noninferiority of IRIS (irinotecan and S-1) to FOLFIRI (irinotecan, folinic acid, and 5-FU) for metastatic colorectal cancer. Meanwhile, in the subset analysis including patients who previously have undergone oxaliplatin-containing chemotherapy, the IRIS group showed longer survival than the FOLFIRI group. However, the molecular mechanism underlying this result is still unknown.Methods:The National Cancer Institute 60 (NCI60) cell line panel data were utilised to build the hypothesis. A total of 45 irinotecan-naive metastatic colorectal cancer patients who had undergone hepatic resection were included for the validation study. The mRNA expressions of excision repair cross-complementing group 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), and topoisomerase-1 (TOP1) were evaluated by quantitative RT–PCR. The expressions of ERCC1 and DPD were also evaluated by immunohistochemistry.Results:Sensitivity to oxaliplatin in 60 cell lines was significantly correlated with that of 5-FU. Resistant cells to oxaliplatin showed significantly higher ERCC1 and DPD expression than sensitive cells. In validation study, ERCC1 and DPD but not TOP1 expressions in cancer cells were significantly higher in FOLFOX (oxaliplatin, folinic acid, and 5-FU)-treated patients (N=24) than nontreated patients (N=21). The ERCC1 and DPD protein expressions were also significantly higher in FOLFOX-treated patients.Conclusion:The ERCC1 and DPD expression levels at both mRNA and protein levels were significantly higher in patients with oxaliplatin as a first-line chemotherapy than those without oxaliplatin. The IRIS regimens with the DPD inhibitory fluoropyrimidine may show superior activity against DPD-high tumours (e.g., tumours treated with oxaliplatin) compared with FOLFIRI.

Changes in expression levels of excision repair cross-complementing group 1 (ERCC1) and dihydropyrimidine dehydrogenase (DPD) during first-line oxaliplatin-based treatment of advanced metastatic colorectal cancer (mCRC).

520 Background: We previously reported the updated results of the FIRIS study, reconfirming the non-inferiority of IRIS (irinotecan/S-1) to FOLFIRI with progression-free survival (PFS) as the primary endpoint (ASCO2011 #3562). Moreover, in patients who had received prior oxaliplatin-based chemotherapy, median OS was significantly longer in the IRIS group than in the FOLFIRI group (adjusted HR=0.755, 95% CI: 0.580–0.987). The aim of this retrospective study was to elucidate molecular mechanisms underlying the better survival in the IRIS group among patients who had previously received oxaliplatin. Methods: Irinotecan-naive mCRC patients (ECOG PS 0–1, adequate organ function, resectable liver metastases) were enrolled. Resected liver metastases were available for 17 patients who had received FOLFOX and 21 patients who had received no prior oxaliplatin-based chemotherapy. Using laser captured microdissection and real-time RT-PCR, we analyzed mRNA expression of excision repair cross complementing group 1 (ERCC1) and dihydropyrimidine dehydrogenase (DPD), factors related to drug resistance and metabolism. Results: Baseline factors (sex, age, histology) of the subjects were similar in the two groups. Expression levels of nucleotide excision repair pathway gene ERCC1 and pyrimidine catabolic pathway gene DPD differed significantly between the FOLFOX group and non-oxaliplatin group. Mean expression levels of ERCC1 and DPD were respectively 1.9 and 7.4 times higher in the FOLFOX group than in the non-oxaliplatin group (ERCC1: 1.58 vs. 0.85, P=0.0005; DPD: 0.580 vs. 0.078, P=0.01). Conclusions: Increased expression of ERCC1 and DPD after first-line oxaliplatin-based chemotherapy is probably related to chemosensitivity to subsequent therapy. Tumor heterogeneity and clonal selection of tumor cells resistant to oxaliplatin may also be involved.

Updated results of the FIRIS study: A phase II/III trial of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer (mCRC).

3562 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of IRIS to FOLFIRI, with progression-free survival (PFS) as the primary endpoint. We now report the final results of this study. Methods: The FIRIS study is a randomized, prospective, open-label, phase II/III study. Irinotecan (IRI)-naïve mCRC patients with one prior chemotherapy regimen, ECOG PS 0–1, and adequate organ function were randomized to receive either FOLFIRI (200 mg/m2 of l-leucovorin given simultaneously with 150 mg/m2 of IRI, followed by a 400 mg/m2 bolus of 5-FU on day 1, and then 2,400 mg/m2 of 5-FU over 46 h, every 2 weeks) or IRIS (125 mg/m2 of IRI on days 1 and 15, and 40–60 mg/body of S-1 twice daily for 2 weeks, followed by a 2-week rest). The primary endpoint was PFS. Secondary endpoints were overall survival (OS), response rate (RR), safety, and treatment cost. Patient information was updated in July 2010. Results: At this final analysis, median follow-up was 3.11 years. Median PFS was 5.1 months (95% CI: 4.2–6.0) in the FOLFIRI group and 5.8 months (95% CI: 4.5–6.0) in the IRIS group (adjusted HR=1.058, 95% CI: 0.869–1.289, p=0.022 for non-inferiority), which is consistent with earlier results (HR=1.077, 95% CI: 0.869-1.319, p=0.039). Median OS was 17.5 months (95% CI: 14.9–19.4) in the FOLFIRI group and 18.0 months (95% CI: 15.0-21.0) in the IRIS group (adjusted HR=0.901, 95%CI: 0.728-1.115 p=0.0003 for non-inferiority). In patients with prior oxaliplatin treatment, median OS was 15.3 and 13.3 months in the IRIS and FOLFIRI groups, respectively (adjusted HR=0.773, 95% CI: 0.593–1.007), whereas in patients without prior oxaliplatin treatment it was 23.6 and 26.9 months, respectively (adjusted HR=1.188, 95% CI: 0.833–1.694). Conclusions: The non-inferiority of IRIS to FOLFIRI, with PFS and OS as endpoints, is reconfirmed. Thus, IRIS can be an additional second line option for mCRC treatment.

Splenomegaly in FOLFOX-naïve stage IV or recurrent colorectal cancer patients due to chemotherapy-associated hepatotoxicity can be predicted by the aspartate aminotransferase to platelet ratio before chemotherapy

Chemotherapy-associated hepatotoxicity is a common cause of postoperative complications after major hepatectomy. Splenomegaly may indicate portal hypertension due to chemotherapy. To identify chemotherapy-naïve patients with liver damage, the splenic volume (SV) and aspartate aminotransferase to platelet ratio (APR) were investigated. Seventy-one patients receiving FOLFIRI, FOLFOX, or FOLFOX plus bevacizumab as first-line chemotherapy were included in this study. The SV measurement was performed by helical computed tomography volumetry, and the SV index (SVI) was calculated during 6 cycles of chemotherapy. The APR was used as an indicator of liver injury and the APR index (APRI) was calculated. The SVI and APRI were significantly higher in the FOLFOX group than in the FOLFIRI group. In the FOLFOX group, the maximum APR during FOLFOX administration was significantly higher in the subjects with SVI ≥ +30% than in those with SVI < +30% (p < 0.01). The incidences of grade 3 or 4 adverse events and grade 2 or greater histopathological sinusoidal injury were significantly higher in the SVI ≥ +30% than in the SVI < +30% group. Interestingly, the SVI was significantly higher in the group with APR ≥ 0.17 before FOLFOX than in the subjects with an APR < 0.17 before FOLFOX (p < 0.05). Splenomegaly due to FOLFOX-associated hepatotoxicity can be predicted if the APR before FOLFOX is 0.17 or higher.

Evaluation of bevacizumab combined with irinotecan-based regimen as the first-line treatment for patients with metastatic colorectal cancer

To assess the efficacy and safety of bevacizumab plus irinotecan-based regimen for the first line treatment in metastatic colorectal cancer (mCRC) patients, and to investigate the correlation between serum tumor markers including CEA and CA19-9 and response as well as prognosis. From May 2007 to July 2008, 67 previously untreated mCRC patients received treatment of IFL (n = 25), IFL plus Bevacizumab (n = 20) or FOLFIRI (n = 22). The treatment continued until disease progression or unacceptable toxicity. The data were retrospectively analyzed. All patients were evaluable for response, survival and toxicity analysis. The objective response rate of IFL, IFL plus Bevacizumab or FOLFIRI regimen groups was 16.0% (4/25), 35.0% (7/20) and 18.2% (4/22), respectively (χ(2) = 6.026, P = 0.049). The median progression-free survival (PFS) of IFL plus bevacizumab group was 7.5 months, significantly improved as compared with 3.7 months in the IFL group and 4 months in FOLFIRI group (χ(2) = 11.97, P = 0.003). Of all 67 cases, the one-year survival rate was 47.0%, two-year survival rate was 27.0%, and the median overall survival (OS) was 13.0 months, with no significant difference among the three treatment groups (χ(2) = 3.42, P = 0.18). The serum CEA and CA19-9 levels were decreased after treatment, but with no significant difference among the three groups (P > 0.05). The common toxicity profiles of IFL and FOLFIRI regimens were diarrhea and neutropenia, while the toxicity related to bevacizumab was consistent with that documented in previous literature, such as hypertension, hemorrhage, cardiac toxicity and delayed wound healing. The addition of bevacizumab to irinotecan-based regimen significantly improves the response rate and PFS in first-line treatment for patients with mCRC and its toxicity is well tolerated.

Feasibility and efficacy of capecitabine and FOLFIRI in patients aged 65 years and older with advanced colorectal cancer: a retrospective analysis

A retrospective analysis was conducted to compare the tolerability and efficacy of single-agent capecitabine and 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) in the first-line treatment of patients aged > or =65 years with metastatic colorectal cancer (mCRC). Consecutive patients with mCRC treated at the Military Medical Institute, Warsaw, between January 2003 and June 2008 were eligible. A total of 123 patients were identified (FOLFIRI, n = 67; capecitabine, n = 56). The overall response rate with FOLFIRI was 28.1 versus 16.4% with capecitabine (P = 0.1398). Median time to disease progression with FOLFIRI was 8.8 versus 7.5 months with capecitabine (P = 0.20), and median overall survival was 19.0 versus 15.4 months (P = 0.93). In the FOLFIRI group, neutropenia and anaemia were significantly more frequent than in the capecitabine group. The main non-haematological toxicity was hand-foot syndrome found only in the capecitabine group. Single-agent capecitabine and FOLFIRI are effective first-line regimens in patients aged > or =65 years with mCRC.

Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer

We investigated the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer and sought associations between the mutation status of the KRAS gene in tumors and clinical response to cetuximab. We randomly assigned patients with epidermal growth factor receptor-positive colorectal cancer with unresectable metastases to receive FOLFIRI either alone or in combination with cetuximab. The primary end point was progression-free survival. A total of 599 patients received cetuximab plus FOLFIRI, and 599 received FOLFIRI alone. The hazard ratio for progression-free survival in the cetuximab-FOLFIRI group as compared with the FOLFIRI group was 0.85 (95% confidence interval [CI], 0.72 to 0.99; P=0.048). There was no significant difference in the overall survival between the two treatment groups (hazard ratio, 0.93; 95% CI, 0.81 to 1.07; P=0.31). There was a significant interaction between treatment group and KRAS mutation status for tumor response (P=0.03) but not for progression-free survival (P=0.07) or overall survival (P=0.44). The hazard ratio for progression-free survival among patients with wild-type-KRAS tumors was 0.68 (95% CI, 0.50 to 0.94), in favor of the cetuximab-FOLFIRI group. The following grade 3 or 4 adverse events were more frequent with cetuximab plus FOLFIRI than with FOLFIRI alone: skin reactions (which were grade 3 only) (in 19.7% vs. 0.2% of patients, P<0.001), infusion-related reactions (in 2.5% vs. 0%, P<0.001), and diarrhea (in 15.7% vs. 10.5%, P=0.008). First-line treatment with cetuximab plus FOLFIRI, as compared with FOLFIRI alone, reduced the risk of progression of metastatic colorectal cancer. The benefit of cetuximab was limited to patients with KRAS wild-type tumors. (ClinicalTrials.gov number, NCT00154102.)

Economic analysis of a multicentre, randomised, phase III trial comparing FOLFOXIRI with FOLFIRI in patients with metastatic colorectal cancer in Greece

ABSTRACTIntroduction: An economic evaluation of the irinotecan, leucovorin, 5-fluorouracil (FOLFIRI) combination versus the irinotecan, oxaliplatin, leucovorin, 5-fluorouracil (FOLFOXIRI) regimen in patients with metastatic colorectal cancer was performed in the context of a randomised phase III study.Methods: The trial did not find any differences in efficacy and, therefore, a cost-minimisation analysis was undertaken. Treatment cost accounts for the administration of first and second line chemotherapy, for concomitant medications, for laboratory and other examinations and hospitalisations due to treatment side effects. Unit prices used reflect 2006 and are common among NHS hospitals in Greece.Results: The mean total cost of therapy in the FOLFOXIRI group (€18 344, 95% CI: €16 951–€19 776), was significantly higher than the FOLFIRI group (€12 201, 95% CI: €11 011–€13 427). Mean chemotherapy cost of the FOLFOXIRI group (€9016; 95% CI: €8338–€9669) was significantly higher than that of the FOLFIRI group (€4830; 95% CI: €4435–€5231). The next largest component of cost involves second line drugs, where the average cost per patient was €3306 (95% CI: €2479–€4237) in the FOLFIRI group and €3996 (95% CI: €3196–€4892) in the FOLFOXIRI group. The cost of hospitalisations was €1814 (95% CI: €1672–€1954) in the first group and €2663 (95% CI: €2469–€2859) in the second. The rest of the components represent a small part of the total cost and there are no differences in the two groups.Conclusion: The combination of irinotecan, leucovorin, 5-fluorouracil has the same effectiveness as the combination of irinotecan, oxaliplatin, leucovorin, 5-fluorouracil in patients with metastatic colorectal cancer, nonetheless it is associated with a much lower overall treatment cost and it should be the preferred treatment regimen in this context.

Cetuximab with irinotecan in first-line treatment of epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC): Preliminary safety results (CRYSTAL)

3555 Background: Cetuximab is an IgG1 monoclonal antibody targeting the EGFR with proven activity in previously treated mCRC patients (pts). The modified two-weekly de Gramont regimen of irinotecan with infusional 5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) is a standard for metastatic disease. This randomized trial investigates the effectiveness of cetuximab with this chemotherapy combination versus chemotherapy alone in (pts) with EGFR-expressing mCRC previously untreated for metastatic disease. Methods: This phase III trial compares cetuximab (400 mg/m2 week 1 then 250 mg/m2 weekly) added to FOLFIRI (irinotecan 180 mg/m2, FA 400 mg/m2, 5-FU bolus 400 mg/m2, 2400 mg/m2 infusional 5-FU) (group A) vs. FOLFIRI alone (group B) in pts with EGFR-detectable tumors. 1080 pts are planned to detect a difference of ≥ 2 months in PFS with 80% power. The Data Safety Monitoring Board (DSMB) has performed an independent preplanned safety evaluation of 401 treated pts. Results: Pts (M/F 252/149, median age 62 years [range, 19–84], ECOG performance status [PS]: PS0, 57.1%: PS1, 38.4%: PS2, 4.5%) received at least 3 treatment cycles to date. Of the 401 pts, 83 (20.7%) pts completed/discontinued the trial. There were 11 deaths (2.7%) within 30 days of the last study treatment: 5 related to disease, 3 to chemotherapy, and 3 other (2 unknown, 1 intercurrent illness). Most common adverse events of the pooled safety data were skin reactions, diarrhea and nausea. Conclusions: After review of all relevant safety information by the DSMB, the trial continues. Recruitment was completed with 1220 patients in December 2005. [Table: see text] [Table: see text]

Continuous versus intermittent chemotherapy in metastatic colorectal cancer

3582 Background: The current policy concerning the duration of chemotherapy in metastatic colorectal cancer (MCC) varies considerably (Clin Oncol 1997;9:248) while no benefit of continuous versus intermittent 5-FU was found in a published randomized study (Lancet 2003;361:457). Serious cumulative toxicity is not usually a problem with long-term 5-FU/FA, but this is not the case with contemporary triple regimens (FOLFIRI, FOLFOX). We, therefore, performed a randomized study of continuous versus intermittent FOLFIRI as first line chemotherapy in MCC. Methods: Patients with MCC and ECOG 0–2 were given 6 biweekly courses of FOLFIRI (Irinotecan 180mg/m2 + De Gramont). Patients with response or stable disease were randomized to continue with another 6 FOLFIRI (group A) or discontinue until relapse when 6 FOLFIRI were readministered (group B). Time to progression (TTP) was calculated from study entrance until 1st progression for group A, and 2nd progression for group B, and overall survival (OS) from study entrance until death. Results: Fifty eight (M=38, F=20) patients entered into the study. Two (3.4%) withdrew before evaluation, 1 (1.7%) died of stroke, 1 (1.7%) was lost to FU and 15 (26%) progressed before or at the completion of 6 FOLFIRI. Thirty nine (67%) patients (M=25, F=14), median age 69 (38–79) responded (21=54%) or had stable disease (18=46%) and were randomized: 19 (49%) to group A and 20 (51%) to group B. Median TTP was 8 months 95% CI: 5.3–10.7) for group A and 9 (95% CI: 7.8–10) for group B (p=NS). 10/19 (52%) in group A received 2nd line chemotherapy vs 7/20 (35%) in group B (p=NS). With a median follow-up of 13 months, 21 patients are alive (12 in group A and 9 in group B). Median OS was 21 months (95% CI: 15 - 26.7) in group A vs 15 (95% CI: 12.6 - 17.3) in group B (p=NS), and 18 months (95% CI: 15.5 - 21) for all 39 patients. Conclusions: In MCC, when response or stability has been achieved after 6 courses ofFOLFIRI there seemstobe little more benefit from continuing chemotherapy than from retreating patients at relapse No significant financial relationships to disclose.

What Is the Best Sequence of Chemotherapy in Advanced Colorectal Cancer? Final Results of a Five-Arm Study

One hundred and ninety-three patients were assigned to receive 5-FU/LV, irinotecan and oxaliplatin in five different sequential treatment groups: Mayo Clinic Regimen (MCR) + LV5FU2 (group A); MCR + irinotecan (350 mg/m²) (group B); MCR + FOLFIRI (group C); MCR + FOLFOX4 (group D); FOLFIRI + FOLFOX4 (group E). The results were as follows: group A (32 patients), median overall survival (OS) 14 months, median time to progression (TTP1) 6 months, median TTP2 5 months, response rate (RR1) 22%, RR2 25%; group B (27 patients), OS 11 months, TTP1 6 months, TTP2 3 months, RR1 22%, RR2 19%; group C (43 patients), OS 14 months, TTP1 5 months, TTP2 5 months, RR1 12%, RR2 19%; group D (45 patients), OS 15 months, TTP1 5 months, TTP2 4 months, RR1 18%, RR2 20%; group E (46 patients), OS 19 months, TTP1 9 months, TTP2 5 months, RR1 39%, RR2 25%. There was a significant difference in OS (p < 0.005) between groups E vs. B and A, D vs. B. Sequential therapy with 3 active drugs (FOLFIRI + FOLFOX4) was the most efficacious combination in comparison with any other two drug combinations applied in our study.