Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial.

BACKGROUND: The standard of care for the treatment of locally advanced rectal cancer results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free and metastatic-free survival with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival is reported here. PATIENTS AND METHODS: The study design, participants, and primary endpoint disease-free survival (DFS) have been reported for this multicenter, randomized, open-label, phase 3 trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on MRI, and staged cT3/T4. Key secondary endpoints included overall survival (OS), metastasis-free survival (MFS), and local and metastatic recurrence rate. RESULTS: With a median follow-up of 82.2 months, the 7-year DFS were 67.6% (95% CI 60.7%-73.9%) and 62.5% (95% CI 55.6%-68.6%) (RMST difference 5.73 months; 95% CI 0.05-11.41; p=0.048) in the neoadjuvant chemotherapy and the standard of care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0%-84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8%-77.8%) in the standard of care group (RMST difference 6.1 months; 95% CI 0.93-11.37; p=0.021). The 7-year OS was 81.9% (95% CI 75.8%-86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7-81.2) in the standard of care group (RMST difference 4.37 months; 95% CI 0.35-8.38; p=0.033). The safety profile remained unchanged since the previous analysis. CONCLUSION(S): Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in locally advanced rectal cancer patients and should be considered as a one of the best options of care for these patients.

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.

Nonsteroidal anti-inflammatory drug-induced colonic strictures: two cases and literature review.

We report two patients with large bowel submucosal diaphragm disease associated with nonsteroidal anti-inflammatory drugs (slow release form of diclofenac and phenylbutazone) who were admitted in 1990 and 1991 because of iron deficiency. At colonoscopy, the lumen of the ascending colon was divided into compartments by multiple thin circumferential mucosal membranes. Barium enema showed two short strictures in one patient. Right hemicolectomy was carried out on one patient. The other patient was simply advised to discontinue taking diclofenac and remains well. Such lesions are rare (10 cases have been reported) and resemble those previously described in the small bowel.

A case of association between hepatocellular carcinoma and porphyria variegata.

BACKGROUND: A correlation between acute intermittent porphyria or porphyria cutanea tarda and hepatocellular carcinoma (HCC) has been noted in several studies, but only one case of association between HCC and porphyria variegata has been reported. We therefore report another case of association between HCC and porphyria variegata. METHODS: A 54-year-old nurse with familial porphyria variegata who developed an HCC was studied. The diagnosis of porphyria variegata was made in the course of a familial survey by means of measuring lymphocyte protoporphyrinogen oxidase activity, at a time when the patient had no symptoms. Eighteen years later the patient presented with a firm enlargement of the liver. RESULTS: Histologic examination showed a well-differentiated HCC. The diagnosis was confirmed by positive immunostaining for alpha-foetoprotein antibodies. DISCUSSION: Sixteen months after surgical resection of the HCC the patient was still alive.

[Sarcoidosis and sarcoid reaction associated with Hodgkin's disease]. / Sarcoïdose et réaction sarcoïdosique associées à la maladie de Hodgkin.

The authors report a case of Hodgkin's disease associated with pulmonary and mediastinal sarcoidosis, and they recall the frequency of sarcoid reactions in lymphoma, notably in Hodgkin's disease. The Hodgkin's disease-sarcoidosis association is much less common and sometimes raises difficult diagnostic problems. The physiopathological mechanisms that are possibly involved are analyzed.