Multicenter Analysis of Treatment Outcomes for Systemic Therapy in Well Differentiated Grade 3 Neuroendocrine Tumors (NET G3)

Well-differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications. Commonly applied first-line chemotherapy protocols with cisplatin or carboplatin in combination with etoposide (PE) are less effective in NET G3 than NEC. Suggested alternative treatment protocols have not been studied in first-line therapy of NET G3 so far. We performed a retrospective analysis of patients with NET G3 in the databases of 3 German cancer centers. Out of 142 patients, 136 patients received palliative first-line therapy: overall response rate (ORR) was 35.1% for PE (n = 37), 56.4% for FOLFOX (n = 39), 27.3% for temozolomide/capecitabine (TEM/CAP) (n = 22), 45.0% for streptozotocin/5-fluorouracil (STZ/5-FU) (n = 20), and 16.7% for other (n = 18). Median progression-free survival (PFS) for PE was 6.9 months. Compared to PE, PFS in the other treatment groups was 6.9 months for FOLFOX (p = 0.333), 12.0 months for TEM/CAP (p = 0.093), 4.8 months for STZ/5-FU (p = 0.919), and 14.1 months for other (p = 0.014). In a univariate setting, all non-PE patients combined showed a significantly prolonged PFS vs. PE (9.0 months; p = 0.049) which could not be confirmed in a multivariate analysis. In conclusion, NET G3 with FOLFOX showed the highest ORR, and with TEM/CAP showed the longest PFS. Further prospective evaluation of the optimal therapeutic strategy for this tumor entity is needed.

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Multicenter analysis of treatment outcomes for well differentiated grade 3 neuroendocrine tumors (NET G3).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4607 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4607-4607

Author(s):

Leonidas Apostolidis ◽

Arianna Dal Buono ◽

Elettra Merola ◽

Henning Jann ◽

Dirk Jaeger ◽

...

Keyword(s):

Treatment Outcomes ◽

Neuroendocrine Tumors ◽

Treatment Guidelines ◽

Second Line ◽

First Line ◽

Primary Tumors ◽

Multicenter Analysis ◽

Net G3 ◽

Well Differentiated ◽

Grade 3

4607 Background: Well differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications from 2017 and 2019. Retrospective data suggest that commonly applied first-line chemotherapy protocols with cisplatin or carboplatin in combination with etoposide (PE) are less effective in NET G3 than NEC. Therefore, current treatment guidelines suggest alternative first-line treatment protocols like temozolomide-based (TEM), streptozotocin-based (STZ) and FOLFOX which have only been studied in second-line so far. The aim of this multicenter analysis was to evaluate treatment outcomes for NET G3 with a focus on the efficacy of different first-line regimens. Methods: We performed retrospective analysis of all patients with NET G3 in the NEN databases of 3 German cancer centers. All histopathological findings were reviewed by the investigators in order to comply with the most current WHO classification. Results: A total of 131 patients could be identified. Median Ki67 was 30 %, primary tumors were located in the pancreas in 71 % of cases, 20 patients had a history of prior NET G1/G2 diagnosis. Median overall survival (OS) was 138.1 months with a median follow-up of 20.4 months. 125 patients received palliative first-line therapy: PE n = 34, FOLFOX n = 36, TEM (mostly temozolomide+capecitabine) n = 21, STZ n = 19, other (including targeted agents, somatostatin analogues, PRRT and multimodal combination approaches) n = 15. Overall response (ORR) and disease control rate was 35.3 % and 67.6 % for PE, 52.8 % and 80.6 % for FOLFOX, 28.6 % and 66.7 % for TEM, 47.4 % and 68.4 % for STZ, 20.0 % and 73.3 % for other respectively. Median progression-free survival for PE was 5.2 months. Compared to PE, PFS in the other treatment groups was 6.0 months for FOLFOX (p = 0.164), 12.0 months for TEM (p = 0.059), 5.7 months for STZ (p = 0.519), 14.1 months for other (p = 0.003). All non-PE patients combined showed a significantly prolonged PFS vs. PE (9.0 vs. 5.2 months; p = 0.011). 89 patients received second-line systemic therapy with a median PFS of 5.3 months. Conclusions: In this first multicenter analysis of different treatment strategies for NET G3, patients receiving upfront treatment with non-PE regimens had a significantly prolonged PFS. Of the single defined protocols, FOLFOX showed the highest ORR, and TEM the longest PFS. Further prospective evaluation of the optimal therapeutic strategy for this newly defined tumor entity is needed.

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Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE

Cancers ◽

10.3390/cancers11070909 ◽

2019 ◽

Vol 11 (7) ◽

pp. 909 ◽

Cited By ~ 8

Author(s):

Achyut Ram Vyakaranam ◽

Joakim Crona ◽

Olov Norlén ◽

Dan Granberg ◽

Ulrike Garske-Román ◽

...

Keyword(s):

Evaluation Criteria ◽

Progression Free Survival ◽

Favorable Outcome ◽

First Line ◽

Ki 67 ◽

First Line Therapy ◽

Line Therapy ◽

Radiological Response ◽

Low Toxicity ◽

Grade 3

Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. Radiological response utilized response evaluation criteria in solid tumors 1.1 and toxicity was graded according to common terminology criteria for adverse events version 4. Median 4 (range 3–11) 7.4 GBq cycles of 177Lu-DOTATATE were administered as first-line therapy (n = 13) or because of progressive disease (n = 9). Partial response (PR) was achieved in two and stable disease (SD) in 20 patients. The median overall survival (OS) was 49.6 (range 8.2–139) months and median progression-free survival (PFS) was 21.6 (range 6.7–138) months. Scintigraphic response >50% was achieved in 9/19 (47%) patients. Biochemical response (>50% decrease) of chromogranin A was found in 6/15 (40%) patients and of catecholamines in 3/12 (25%) patients. Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). No hematological or kidney toxicity grade 3–4 was registered. 177Lu-DOTATATE therapy was associated with favorable outcome and low toxicity. High Ki-67 (≥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.

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Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.9898 ◽

2008 ◽

Vol 26 (12) ◽

pp. 2006-2012 ◽

Cited By ~ 532

Author(s):

Jim Cassidy ◽

Stephen Clarke ◽

Eduardo Díaz-Rubio ◽

Werner Scheithauer ◽

Arie Figer ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Folinic Acid ◽

Progression Free Survival ◽

Phase Iii ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Hand Foot Syndrome ◽

Grade 3

PurposeTo evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).Patients and MethodsThe initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 × 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.ResultsThe intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 × 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.ConclusionXELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

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Simplified LV5FU2-irinotecan (FOLFIRI) in the first-line therapy of well-differentiated endocrine carcinomas of the duodeno- pancreatic area: Preliminary results of the FFCD 0302 phase II trial with GTE participation

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4620 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4620-4620

Author(s):

G. Cadiot ◽

F. Bonnetain ◽

B. Landi ◽

O. Bouché ◽

E. Mitry ◽

...

Keyword(s):

Phase Ii ◽

Proliferation Index ◽

Progression Rate ◽

First Line ◽

First Line Therapy ◽

Free Interval ◽

Line Therapy ◽

Well Differentiated ◽

Grade 3 ◽

Endocrine Carcinomas

4620 Introduction: Few chemotherapies have been tested in the first-line treatment of endocrine carcinomas. The aim of the study was to evaluate the efficacy of FOLFIRI in the first-line therapy of evolutive, metastatic or locally invasive, well-differentiated endocrine carcinomas of the duodeno-pancreatic area. Methods: To show a 6-month tumoral non-progression (RECIST) rate ≥ 60% (a = 5%), 20 pts had to be included in a phase II, prospective, multicentric trial. Inclusion criteria were : well-differentiated endocrine carcinoma of the duodeno-pancreatic area, functioning or non functioning, with hepatic or extra-hepatic metastases or locally invasive tumor > 50 mm, not resectable; tumoral growth within 6 months; no previous antitumoral therapy except interferon ( = 3 months) or somatostatin analogs; PS 0–2. Treatment administration every 14 days : D1 : irinotecan 180 mg/m2, folinic acid 400 mg/m2, 5 FU 400 mg/m2 bolus; D1-D2 : 5 FU 2,400 mg/m2 in 46 hrs. Evaluation (clinical, radiological, biological) every 3 months. In case of progression during a chemotherapy free-interval following an objective tumoral response, treatment was reintroduced. All analyses were performed in intent to treat. Data cut off was done at July 1st 2006. Results: Between May 2004 and July 2005, 20 pts (13 M, 7 F) were included with median age 57 yrs (37–82). 19 pts had liver metastases and 1 pt had metastatic lymph nodes. 5 tumors were functioning; 2 pts had MEN 1. Median proliferation index was 7% (0–58). All pts were treated and evaluation at 6 months for the primary endpoint was available in 19 pts. The 6-month non-progression rate was 75% (CI 95% = 51–91%,), including 14 stabilization (70%) and 1 partial response (5%). 4 pts had 1 chemotherapy free-interval and 2 pts had 2 with reintroduction of the same chemotherapy regimen. Median number of cycles was 11.5 (1–28). 80% had at least 1 grade 3–4 toxicity and 25% had grade 3–4 hematological toxicity. 10% had grade 3 diarrhoea.. Conclusion: FOLFIRI has an antitumoral effect in the first-line therapy of evolutive well-differentiated pancreatic endocrine carcinomas. Frequency of grade 3–4 toxicities can be explained by length of therapy. No significant financial relationships to disclose.

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Assessment for markers of poor prognosis in a real-world evidence study of treatment patterns in patients with HR+/HER2- locally advanced or metastatic breast cancer in Korea and Taiwan.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13083 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13083-e13083

Author(s):

Diego Novick ◽

Narayan Rajan ◽

Rebecca Ming-Huei Cheng ◽

Sae Young Lee ◽

Dong Hyun Koo ◽

...

Keyword(s):

Locally Advanced ◽

Metastatic Breast ◽

Progression Free Survival ◽

Patient Characteristics ◽

First Line ◽

Free Survival ◽

Median Progression Free Survival ◽

First Line Therapy ◽

Line Therapy ◽

Grade 3

e13083 Background: To assess how patient characteristics impact treatment patterns and real-world effectiveness among patients with hormone receptor (HR+)/human epidermal growth receptor 2-negative (HER2-) locally advanced and metastatic breast cancer (ABC) in Korea and Taiwan. Methods: We conducted a retrospective chart review comprising 227 female patients aged ≥ 18 years and diagnosed HR+/HER2- ABC in Korea and Taiwan between 2015-2017. Those having at least one of the following characteristics, shown previously to negatively impact prognosis, formed the poor prognostic cohort (PPC): ECOG PS > 0, not bone-only disease, liver metastases, or negative PgR status. Anonymized data on patient characteristics, treatment pathways, progression-free survival, and grade 3 or higher adverse events (AEs) of interest was abstracted. Descriptive statistics and Kaplan Meier methods were used to assess the outcomes. Results: The mean (range) age was 57.1 (29 - 83) years. A total of 193 (85.0%) patients were PPC. Endocrine regimens were the most frequent first-line therapies used by 50.3% and 67.6% of patients in the PPC and non-PPC cohorts, respectively. Chemotherapy regimens were used by 25.9% and 17.6% as initial systemic therapy and by 60.1% and 35.3% at any time following diagnosis of ABC, for PPC and non-PPC, respectively. The median progression-free survival time, based on first-line therapy, was 8.3 (95%CI: 6.9 – 10.4) months for PPC versus 11.5 (95%CI: 5.5 – 12.0) months in non-PPC. The proportion of patients with at least 1 grade 3 or higher AEs of interest during first-line therapy was higher in the PPC cohort compared to the non-PPC cohort, 54.4% vs. 44.1% respectively. The most common AEs reported were leukopenia, asthenia/fatigue and neutropenia occurring in 27.5%, 28.0% and 20.7% of the PPC cohort and 23.5%, 2.9%, and 14.7% of the non-PPC cohort, respectively. Conclusions: The existence of one or more poor prognostic factors is associated with a higher chemotherapy use any time following diagnosis of ABC, as well as lower median progression-free survival and a higher likelihood of having an adverse event during first line therapy, compared to non-PPC cohort. These results suggest that patient poor prognostic characteristics can be drivers for therapy selection.

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Endostatin combined with chemotherapy as first-line therapy for stage IV melanoma patients: A phase II clinical study

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e20003 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e20003-e20003

Author(s):

C. Cui ◽

Z. Chi ◽

X. Yuan ◽

L. Si ◽

X. Sheng ◽

...

Keyword(s):

Sinus Bradycardia ◽

Stage Iv ◽

Progression Free Survival ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Phase Ii Clinical Study ◽

Melanoma Patients ◽

Grade 3 ◽

Stage Iv Melanoma

e20003 Background: To observe the efficacy and safety of rh-endostatin injection (Endostar) combined with chemotherapy as first line therapy for stage IV melanoma patients. Methods: From March 2007-March 2008, 20 metastatic melanoma patients were enrolled. Endostar (15 mg d1–14) combined with dacarbazine (250 mg/m2 d1–5) or temozolomide (300 mg d 1–5) and fotemustine (100 mg/m2 d6) were given every 28days. Response, toxicity and progression free survival(PFS) were analyzed. Results: Among 20 evaluable cases, with mean cycle 2.7±0.80, four achieved partial response, six stable disease, with response rate 20.0% (4/20) and clinical benefit rate 50.0% (10/20). The median PFS reached 4.5 months (95% CI: 3.85–6.9 months), overall survival 8.5 months (95% CI: 5.62–8.54 months), with 6 months PFS rate 35% (7/20), and 6 months survival rate 65% (13/20). The Grade 3/4 toxicity was mainly myelosuppression, 40% (8/20). One patient ceased the treatment because of sinus bradycardia. Conclusions: Endostar combined with chemotherapy show its efficacy on melanoma patients and may prolong PFS. No significant financial relationships to disclose.

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Endostar plus gemcitabine/cisplatin (GP) with maintenance endostar as first-line therapy for advanced non-small cell lung cancer (NSCLC): Preliminary results of a phase II study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18033 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18033-e18033

Author(s):

You Lu ◽

Meijuan Huang ◽

Qingxia Fan ◽

Qi Wu ◽

Jin Wang ◽

...

Keyword(s):

Survival Rate ◽

Advanced Nsclc ◽

Objective Response ◽

Stage Iv ◽

Progression Free Survival ◽

Hematologic Toxicity ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Grade 3

e18033 Background: Endostar is a recombinant human endostatin. We conducted a multi-centre trial to investigate the efficacy and safety of Endostar plus GP with maintenance Endostar as first- line therapy for advanced NSCLC Methods: Chemotherapy-naïve patients with histologically or cytologically confirmed, measurable, stage ‡W NSCLC were enrolled from 11 centers in China. All patients received gemcitabine 1,000 mg/m2 (days 1 and 8) plus cisplatin 25 mg/m2 (days 1-3) every 21 days. Patients achieving objective response or disease stabilization following initial 2 cycles of GP were given Endostar (15 mg) on days 1–14 every 21 days in combination with another 2 cycles of GP. Then, patients who did not progress received maintenance endostar (15 mg) on days 1–14 every 21 days until disease progression or unacceptable toxicity. The primary was progression-free survival (PFS). Secondary endpoints were treatment-related toxicity and median overall survival (OS). Results: Between Oct.2008 and Sep. 2010, we enrolled 85 patients (median age: 52.2 years; median KPS score: 80; stage IV with M1b: 94.1%; adenocarcinoma: 64.6%). 48 (56.5%) patients complete 4 cycles of GP plus 2 cycles of Endostar and 33(38.8%) patients were treated with maintenance Endostar. For 38 patients receiving maintenance therapy, median PFS throughout the study period by independent review was 5.97 month and 1-year survival rate was 75.8%. Median PFS were 3.97 months for all 85 patients, while 1-year survival rate was 64.7%. No treatment related death occurred. 28(32.9%) patients had at least one grade 3/4 adverse events; the grade 3/4 hematologic toxicity included anemia in 32.9%, thrombocytopenia in 25.9%, neutropenia in 4.7% of patients. The grade 3/4 non-hematologic toxicities included nausea/vomiting in 18.8%, rash in 5.9%, hepatic impairment in 3.5%, diarrhea in 1.2%, hemorrhage in 1.2% of patients. Conclusions: This regimen, involving maintenance Endostar, didn’t significantly improve PFS in advanced NSCLC patients as compared to historic control although associated acceptable toxicity has been demonstrated

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7512 ◽

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]

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FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study

Journal of Clinical Oncology ◽

10.1200/jco.2004.05.113 ◽

2004 ◽

Vol 22 (2) ◽

pp. 229-237 ◽

Cited By ~ 2048

Author(s):

Christophe Tournigand ◽

Thierry André ◽

Emmanuel Achille ◽

Gérard Lledo ◽

Michel Flesh ◽

...

Keyword(s):

Colorectal Cancer ◽

Folinic Acid ◽

Progression Free Survival ◽

Similar Efficacy ◽

Phase Iii ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Phase Iii Study ◽

Grade 3

Purpose In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B). Patients and Methods Previously untreated patients with assessable disease were randomly assigned to receive a 2-hour infusion of l-LV 200 mg/m2 or dl-LV 400 mg/m2 followed by a FU bolus 400 mg/m2 and 46-hour infusion 2,400 to 3,000 mg/m2 every 46 hours every 2 weeks, either with irinotecan 180 mg/m2 or with oxaliplatin 100 mg/m2 as a 2-hour infusion on day 1. At progression, irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm B). Results Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI (P = .99). Median second progression-free survival (PFS) was 14.2 months in arm A versus 10.9 in arm B (P = .64). In first-line therapy, FOLFIRI achieved 56% response rate (RR) and 8.5 months median PFS, versus FOLFOX6 which achieved 54% RR and 8.0 months median PFS (P = .26). Second-line FOLFIRI achieved 4% RR and 2.5 months median PFS, versus FOLFOX6 which achieved 15% RR and 4.2 months PFS. In first-line therapy, National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis, nausea/vomiting, and grade 2 alopecia were more frequent with FOLFIRI, and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6. Conclusion Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.

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