FOLFIRINOX as induction treatment in rectal cancer patients with synchronous metastases: Results of the FFCD 1102 phase II trial.

AIM OF THE STUDY: The optimal therapeutic strategy in patients with rectal cancer and synchronous unresectable metastases remains unknown. We evaluated the efficacy of FOLFIRINOX induction therapy in this setting. PATIENTS AND METHODS: Chemotherapy-naïve patients received at least 8 cycles of FOLFIRINOX. The primary end-point was the 4-month disease control (4 m DC) rate. Tumour responses were centrally reviewed and assessed by computed tomography scan for metastases (Response Evaluation Criteria in Solid Tumours criteria) and magnetic resonance imaging for rectal tumorus. With a Simon 2-stage design and a targeted (H1) 4 m DC > 75%, 65 patients were enrolled from July 2012 to February 2015: male, 78%; median age, 61 years; performance status, 0-1, 98%; liver metastases, 92%; ≥2 metastatic sites, 63%. RESULTS: Fifty-six (85%) of the 65 patients received the 8 planned FOLFIRINOX cycles. The primary objective was achieved (4 m DC rate: 94%; 95% confidence interval [CI], 86.3-97.8). Primary tumour symptoms decreased from 72% at baseline to 10% at 4 months. Response rate was 86%, and a >70% primary tumour volume decrease was seen in 63% of patients. Forty-four patients (68%) had at least one grade 3 side-effect; no toxic deaths occurred. Median follow-up was 35.0 months (95% CI, 31.3-43.7). Median progression-free survival and overall survival were 10.9 m (95% CI, 8.8-12.9) and 33.4 m (95% CI, 22.6-38.2), respectively. CONCLUSION: Upfront FOLFIRINOX is feasible and allows good local and distant control. It therefore offers the opportunity to choose the best therapeutic strategy for each patient and to personalise treatment according to the local and distant efficacy results of this induction step. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01674309.

Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02).

BACKGROUND: Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS: Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS: From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION: In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV: NCT00303771.

Some diminutive colorectal polyps can be removed and discarded without pathological examination.

BACKGROUND AND STUDY AIMS: Pathological examination of colorectal polyps is useful if clinical management is affected (i. e. when invasive carcinoma is detected or postpolypectomy surveillance interval is guided). Our aim was to assess whether the pathological examination of some diminutive (measuring ≤ 5 mm) polyps can be omitted. PATIENTS AND METHODS: Consecutive patients undergoing a colonoscopy at Pasteur Hospital (Colmar, France) between January and August 2008 were included in this prospective study. Six senior gastroenterologists predicted the future surveillance interval without referring to the result of pathological examination. RESULTS: In all, 350 polyps from 175 patients were removed and analyzed. The endoscopist was able to predict the correct surveillance interval without referring to the result of pathological examination in 118 patients (67.4 %; 95 % confidence interval [CI] 60.5 - 74.4). The pathological examination of 18.4 % (95 % CI 13.7 - 23.1) of diminutive polyps either associated with a cancer or a polyp measuring ≥ 10 mm or removed in very old or frail patients could be omitted without any consequence for the patient. If diminutive polyps one or two in number were discarded without pathological examination in patients with a personal history of colorectal neoplasm, three patients out of 43 would have a 5-year instead of a 3-year surveillance interval. As a whole, if 44.1 % (95 % CI 38.0 - 50.1) of diminutive polyps were discarded, the surveillance interval would remain identical in 98.3 % (95 % CI 96.4 - 100) of patients. CONCLUSIONS: The pathological examination of up to 44 % of diminutive polyps (i. e. 33 % of all polyps), can be safely omitted. The pathological examination would be required only for those with suspicious gross appearance, those three or more in number, and those isolated one or two in number that are removed from people without personal history of colorectal neoplasm.

Validation of the French version of the colorectal-specific quality-of-life questionnaires EORTC QLQ-CR38 and FACT-C.

BACKGROUND: The aim of this study was to test the psychometric properties of the French version of the European Organization for Research and Treatment (EORTC) quality-of-life colorectal questionnaire (QLQ-CR38) and the functional assessment of cancer therapy-colorectal version 4 (FACT-C). METHOD: This prospective study included 209 patients with colorectal cancer: 71 undergoing chemotherapy, 56 radiation, 15 surgery, and 67 survivors. Patients first completed in random order the FACT-C and the EORTC QLQ-CR38 and were asked if they had any preference for either questionnaire. The timing of administration of instruments differed according to patients' treatment to better assess psychometric properties. RESULTS: The FACT-C showed good acceptability, good reproducibility and excellent internal consistency. The QLQ-CR38 had lower internal consistency. Patients did not express a preference for one survey over another. CONCLUSION: This study confirms the value of the FACT-C and suggests some limits of the QLQ-CR38 for patients with colorectal cancer.