Evaluation in usual practice of the bevacizumab-FOLFIRI combination for the first-line treatment of patients with unresectable metastatic colorectal cancer treated in 2006: focus on resected patients and oncogeriatrics: AVASTIN OUEST cohort of the Observatory of Cancer of the Brittany and Pays de la Loire Areas (Observatoire dédié au Cancer Bretagne / Pays de la Loire).

BACKGROUND: In 2006, bevacizumab, a targeted therapy agent was combined with FOLFIRI for the firstline treatment of patients with unresectable metastatic colorectal cancer. METHODS/RESULTS: A study on a homogenous series of 111 patients from the Brittany and Pays de la Loire areas who received bevacizumab-FOLFIRI as first-line treatment in 2006 showed the following results: 51 responses, 29 stabilisations, 21 progressions and 10 cases of toxicity prior to assessment. Median overall survival (OS) was 25.1 months and median progression-free survival was 10.2 months. Surgery secondary to treatment tripled median OS which reached 59.2 months in resected patients versus 18.8 months in unresected patients. Comparison of patients aged more or less than 70 years showed no differences in terms of benefits or risks. CONCLUSION: Bevacizumab-FOLFIRI could be administered as part of a routine care protocol to elderly patients previously evaluated by a geriatric assessment and validated by a multidisciplinary staff.

En 2006, bevacizumab-FOLFIRI représente la thérapie ciblée administrable dès la première ligne chez les patients porteurs d'un cancer colorectal métastatique non opérable. Une série homogène de 111 patients colligés en région Bretagne et Pays de la Loire ayant reçu du bevacizumab- FOLFIRI en première ligne en 2006 révèle les résultats suivants: 51 réponses, 29 stabilités, 21 progressions et 10 toxicités avant évaluation. La médiane de survie globale (OS) est de 25,1 mois et la médiane de survie sans progression (PFS) de 10,2 mois. Dans le cas d'une chirurgie secondaire, l'OS médian triple de 18,8 mois chez les patients non réséqués versus 59,2 mois ceux réséqués. En comparant les sujets âgés de plus et de moins de 70 ans, aucune différence n'a été mise en évidence en termes de bénéfice ou de risque. Bevacizumab-FOLFIRI pourrait être administré en pratique courante chez les personnes âgées sous couvert d'une évaluation gériatrique et d'une approche multidisciplinaire.

Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial.

BACKGROUND: The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC). PATIENTS AND METHODS: Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT. RESULTS: The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively. CONCLUSION: CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings. EUDRA CT NO: 2007-007029-38.

PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

Cervico-facial adenoid cystic carcinoma: study of 102 cases. Influence of radiation therapy.

One hundred two patients with cervico-facial adenoid cystic carcinoma were treated with surgery alone, radiotherapy alone or both from 1951 to 1980. All the cases have a 5-year minimum follow-up. The local control rate is 55.5% at 5 years and 37.7% at 10 years. The 5-year local control rate is 44% with surgery alone, 65.8% with radiotherapy alone and 77.8% with post-operative radiotherapy. The difference between surgery alone and radiosurgical association is significant (p less than 0.01). The bone involvement diminished local control rate (32.2%/k 68.8%). The 5-year survival rate of the patients who recurred and have been retreated is 70.5%. The 5-year survival rate of the patients after the appearance of a metastasis is 38.1% and 2 patients have survived more than 10 years. The NED 5-year survival rate is 48.8%. There is no significant difference in the NED 5-year survival rate according to sites or treatments. The crude 5-year survival rate is 70%, 51.4% at 10 years and 32.2% at 15 years. Our study shows that adenoid cystic carcinoma have a peculiar and slow evolution. Surgery with post-operative radiotherapy obtains the best local control. These results and the radiosensibility of these lesions allow us to propose an aggressive treatment for the recurrence and the primary tumor of the directly metastatic patients.

A retrospective study of three treatment techniques for T1-T2 base of tongue lesions: surgery plus postoperative radiation, external radiation plus interstitial implantation and external radiation alone.

One hundred and ten patients with base of tongue tumors less than or equal to 4 cm in diameter (T1 and T2 by the UICC staging system) were treated according to three different methods; surgery followed by external radiation in 27 cases, external radiation followed by interstitial implantation in 29 cases, and external radiation alone in 54 cases. The median follow-up is 8 years with a minimum of 4 years. Local failure occurred twice as often in patients treated by external radiation alone (43%) compared to the other two therapeutic modalities (20.5% for external radiation plus implantation and 18.5% for surgery plus radiation). Ninety per cent of recurrences occurred within the first 2 years. The 5-year survival rate for N0 and N1 nodal disease is 30.5% for patients treated by external radiation alone and 50% for the other two methods. This survival difference is related to poorer local control. Surgery plus external radiation gives identical results to those of external radiation and interstitial implantation, but surgery is only practical for peripheral base of tongue tumors and it has poorer functional results. External radiation followed by interstitial implantation is, in our opinion, the best of the three therapeutic techniques for T1 and T2 base of tongue tumors.

[Cervical intraepithelial neoplasms and flat condylomata. Study of 165 cases]. / Néoplasies cervicales intra-épithéliales et condylomes plans. Etude de 165 cas.

205 cervix biopsies and diagnostic conisations performed among 165 women with dysplasias and carcinomas in situ (CIS) where revised with actual concepts of flat condylomata (FC) and cervical intraepithelial neoplasias (CIN). Usual statistical tests were used to analyse the signification of the average age of the different group (FC alone, FC + CIN, CIN alone) and according to the different grades of CIN. The association between FC and the different grades of CIN was studied with the X2 test. In 66.8% of the cases, FC was present, associated or not with CIN. That ends up to a modification of the diagnosis in 37.6% of the cases (reduction of a grade of CIN, substitution of a mild dysplasia CIN I by a FC). In 33.8% of the cases, FC was associated with CIN. In this work, the average age between CIN associated with FC was 8 years less than CIN alone. The X2 test applied to the frequency of association between FC and CIN according to the grade of CIN have shown that it exists a statistically valid difference between the grades. More the grades is high, more the morphological characters of the FC are rare. These observations suggest an integration of the viral genome in the host genome as it has been proved for the shope papilloma and the verruciformis epidermodysplasia.

[Pelvic cancers: radioprotection of the small intestine by using a mammary prosthesis for postoperative irradiation. Apropos of 12 cases]. / Cancers pelviens: radio-protection du grêle par prothèse mammaire pour irradiation post-opératoire. A propos de 12 observations.

A preventive technique of radiation injuries to small intestines with intrapelvic mammary prosthesis is described. It has been used for twelve cases in which 9 concerned rectal adenocarcinomas (local recurrences 7 and fixated tumors 2). After this short experience, we can recommend this reliable technique without important local complication and describe the irradiation technique. The indications of this method are precised because it is finally an unfrequent therapeutic.

[Cancers of the base of the tongue and hypopharynx: results of a multicenter randomized trial of chemotherapy prior to locoregional treatment]. / Cancers de la base de langue et de l'hypopharynx: résultats d'un essai multicentrique randomisé de chimiothérapie avant traitement locorégional.

The authors report the results of a multicentric randomised trial assessing the effects on survival of neoadjuvant chemotherapy with cisplatin (100 mg/m2, D1) and fluorouracil (1 g/m2, D2-4) delivered before regional treatment in patients with squamous cell carcinoma of hypopharynx and base of tongue. 133 patients were enrolled in the study, and 121 were included in the analysis, 64 in group A (regional treatment alone) and 27 in group B (chemotherapy followed by regional treatment). Despite a high objective response rate to chemotherapy (primary tumour: 85%, 24% complete; nodes: 63%), overall survival was not significantly higher in group B than in group A.