Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

Nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil as first-line therapy for metastatic pancreatic adenocarcinoma (AFUGEM GERCOR): a non-comparative, multicentre, open-label, randomised phase 2 trial.

BACKGROUND: Nab-paclitaxel plus gemcitabine has become a standard treatment regimen in patients with metastatic pancreatic adenocarcinoma; however, retrospective data suggest that gemcitabine might be inefficient in 50-60% of patients and thus not an optimum regimen in combination with nab-paclitaxel. We did a phase 2 trial to assess the activity and safety of a new regimen of nab-paclitaxel plus simplified leucovorin and fluorouracil. METHODS: We did a non-comparative, multicentre, open-label, randomised phase 2 trial in 15 hospitals and institutions in France. Eligible participants were previously untreated patients with metastatic pancreatic adenocarcinoma (previous adjuvant chemotherapy after curative intent resection was allowed if the interval between the end of chemotherapy and relapse was more than 12 months). Patients had to have at least one measurable lesion assessed by CT scan or MRI and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. We randomly assigned participants (1:2) centrally to 28-day cycles of either gemcitabine plus nab-paclitaxel or simplified leucovorin and fluorouracil plus nab-paclitaxel. The randomisation was by minimisation, stratified by centre and ECOG performance status. Drugs were administered in each cycle as follows: nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) as 30-min intravenous infusions on days 1, 8, and 15; leucovorin (400 mg/m2) as a 120-min intravenous infusion on days 1 and 15; and fluorouracil (400 mg/m2) as a 5-min bolus intravenous infusion followed by a 46-h continuous intravenous infusion of 2400 mg/m2 on days 1 and 15. Patients continued treatment until unacceptable toxicity, disease progression, or patient withdrawal. The primary endpoint was progression-free survival at 4 months in the first 72 assessable patients in the leucovorin and fluorouracil group, with a target of 50% for the regimen to be deemed sufficiently active to warrant further study. We did the primary analysis on the modified intention-to-treat (ITT) population, defined as all randomly assigned and assessable patients regardless of their eligibility and received treatments. This trial is registered at ClinicalTrials.gov, number NCT01964534. The trial has ended and we report the final analysis here. FINDINGS: Between Dec 12, 2013, and Oct 31, 2014, we randomly assigned 114 patients to treatment: 75 patients to the leucovorin and fluorouracil group and 39 to the gemcitabine group. One patient in the leucovorin and fluorouracil group did not have a 4-month assessment, and was thus excluded from the modified ITT analysis. Median follow-up was 13·1 months (95% CI 12·5-14·1). At 4 months, 40 (56%, 90% CI 45-66) of 72 patients in the leucovorin and fluorouracil group were alive and free from disease progression (21 [54%, 40-68] of 39 patients in the gemcitabine group were also alive and progression-free at 4 months). Grade 3-4 adverse events occurred in 33 (87%) of 38 patients in the gemcitabine group and in 56 (77%) of 73 patients in the leucovorin and fluorouracil group, with different toxicity profiles. The most common grade 3-4 adverse events in the leucovorin and fluorouracil group were neutropenia without fever (17 [23%]), fatigue (16 [22%]), paraesthesia (14 [19%]), diarrhoea (nine [12%]), and mucositis (seven [10%]); in the gemcitabine group they were neutropenia without fever (12 [32%]), thrombocytopenia (seven [18%]), fatigue (eight [21%]), anaemia (five [13%]), increased alanine aminotransferase and aspartate aminotransferase concentrations (five [13%] for both), and paraesthesia (four [11%]). Two participants died; one in the leucovorin and fluorouracil group from septic shock, and one in the gemcitabine group from diabetes compensation with acidosis; these deaths were deemed to be not related to treatment. Treatment-related serious adverse events occurred in 28 (38%) of 73 patients in the leucovorin and fluorouracil group and in 14 (37%) of 38 in the gemcitabine group. INTERPRETATION: Nab-paclitaxel plus simplified leucovorin and fluorouracil fulfilled the primary endpoint in that more than the required 50% of our study population were progression-free at 4 months, with a tolerable toxicity profile. This regimen thus deserves further assessment in a phase 3 trial. FUNDING: GERCOR (Groupe Coopérateur Multidisciplinaire en Oncologie) and Celgene through grants to GERCOR.

Feasibility of Capecitabine and Oxaliplatin Combination Chemotherapy Without Central Venous Access Device in Patients With Stage III Colorectal Cancer.

BACKGROUND: 5-Fluorouracil and leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (XELOX) is a standard adjuvant treatment for patients with stage III colon cancer (CC). Capecitabine is an oral fluoropyrimidine, and administration of oxaliplatin does not necessarily require the insertion of a central venous access device (CVAD). We evaluated the feasibility of XELOX without a CVAD as adjuvant treatment in patients with stage III CC. PATIENTS AND METHODS: We retrospectively studied prospectively collected data from patients with stage III CC treated with XELOX in the International Duration Evaluation of Adjuvant Chemotherapy French trial. Patients were divided into 2 groups: those with a CVAD and those with peripheral venous access (PVA), including patients who had and had not had a CVAD at the first cycle of chemotherapy. Chemotherapy without a CVAD was considered feasible if the patient received all cycles of adjuvant therapy without it. RESULTS: A total of 203 patients were included: 86 (43%) in the PVA group and 116 (57%) in the CVAD group. Of the 85 patients in the PVA group (1 patient was not treated), 69 (81.2%) did not require the insertion of a CVAD. However, 16 (18.8%) required CVAD insertion owing to systematic delay of the initially planned CVAD before the second cycle of chemotherapy in 7, complications related to PVA usage in 5, a switch to the modified FOLFOX6 regimen in 2, and other reasons in 2. The oxaliplatin dose was similar in both groups regardless of the chemotherapy duration. XELOX without a CVAD was feasible for 81.2% of the patients for whom a CVAD had not been planned before chemotherapy and for 88.4% of patients for whom chemotherapy was planned without the use of a CVAD. CONCLUSION: XELOX chemotherapy without a CVAD is a feasible approach for treating patients with stage III CC in the adjuvant setting.

Nutritional advice in older patients at risk of malnutrition during treatment for chemotherapy: a two-year randomized controlled trial.

OBJECTIVE: We tested the effect of dietary advice dedicated to increase intake in older patients at risk for malnutrition during chemotherapy, versus usual care, on one-year mortality. METHOD: We conducted a multicentre, open-label interventional, stratified (centre), parallel randomised controlled trial, with a 1∶1 ratio, with two-year follow-up. Patients were aged 70 years or older treated with chemotherapy for solid tumour and at risk of malnutrition (MNA, Mini Nutritional Assessment 17-23.5). Intervention consisted of diet counselling with the aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d, by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Interviews were performed 6 times during the chemotherapy sessions for 3 to 6 months. The primary endpoint was 1-year mortality and secondary endpoints were 2-year mortality, toxicities and chemotherapy outcomes. RESULTS: Between April 2007 and March 2010 we randomised 341 patients and 336 were analysed: mean (standard deviation) age of 78.0 y (4·9), 51.2% male, mean MNA 20.2 (2.1). Distribution of cancer types was similar in the two groups; the most frequent were colon (22.4%), lymphoma (14.9%), lung (10.4%), and pancreas (17.0%). Both groups increased their dietary intake, but to a larger extent with intervention (p<0.01). At the second visit, the energy target was achieved in 57 (40.4%) patients and the protein target in 66 (46.8%) with the intervention compared respectively to 13 (13.5%) and 20 (20.8%) in the controls. Death occurred during the first year in 143 patients (42.56%), without difference according to the intervention (p = 0.79). No difference in nutritional status changes was found. Response to chemotherapy was also similar between the groups. CONCLUSION: Early dietary counselling was efficient in increasing intake but had no beneficial effect on mortality or secondary outcomes. Cancer cachexia antianabolism may explain this lack of effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT00459589.