Biweekly docetaxel, fluorouracil, leucovorin, oxaliplatin (TEF) as first-line treatment for advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: safety and efficacy in a multicenter cohort.

BACKGROUND: Docetaxel-cisplatin-5-FU chemotherapy is superior to 5-FU-cisplatin in terms of response rate and survival in advanced gastric cancer (AGC), but is more toxic. Oxaliplatin is better tolerated than cisplatin, which it can effectively replace in this setting. We hypothesize that incorporating docetaxel into a simplified FOLFOX regimen should be a tolerable and effective option in first-line treatment of AGC. METHODS: Data were collected at six French centers from patients with metastatic or local AGC who received docetaxel, fluorouracil, leucovorin, or oxaliplatin (TEF) as first-line treatment. TEF was administered as follows: docetaxel (50 mg/m(2)), oxaliplatin (85 mg/m(2)), and leucovorin (40 mg/m(2)) on day 1, and 5-FU continuous infusion for 48 h (2400 mg/m(2)) every 2 weeks. RESULTS: Forty-one patients were enrolled. Performance status was grade 0 and 1 in respectively 27 and 58 % of patients; 17 patients had adenocarcinoma of the gastroesophageal junction; 37 patients had metastatic disease, 22 had a poorly differentiated or diffuse type. Objective response rate was 66 %, with a complete response in two patients (5 %). Median progression-free survival and overall survival were respectively 6.3 and 12.1 months. Tolerability was acceptable with no treatment-related deaths. The most frequent grade 3-4 toxicities were neutropenia (30 %) and neuropathy (12.5 %). Curative intent surgery after response to TEF was performed in seven patients (17 %). CONCLUSION: TEF is an effective first-line treatment with an acceptable toxicity profile for patients with AGC. It may allow curative resection in initially unresectable patients. TEF should now be evaluated in prospective randomized trials.

Encorafenib plus cetuximab treatment in BRAF V600E-mutated metastatic colorectal cancer patients pre-treated with an anti-EGFR: An AGEO-GONO case series.

BACKGROUND: Encorafenib plus cetuximab is efficient in anti-EGFR-naïve patients with BRAFV600E mutated (BRAFm) metastatic colorectal cancer (mCRC). No data are available concerning the efficacy of BRAF inhibitors associated with anti-EGFRs (B + E) in patients previously treated with an anti-EGFR agent. METHODS: We retrospectively collected a series of patients with BRAFm mCRC treated with B + E after previous anti-EGFR treatment, in 14 centers. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment, and we reported objective response and disease control rates (ORR, DCR; RECIST V1.1). RESULTS: Twenty-five BRAFm mCRC patients were enrolled. Prior to B + E treatment, 4/10/11 patients were treated with 1/2/> 2 previous treatment lines. Ten patients received previous panitumumab, 14 cetuximab, 1 both. Immediate progression with previous anti-EGFR was reported for 7 patients. Anti-BRAF was encorafenib for 21 patients, dabrafenib for 4 patients, with cetuximab for 24 patients and panitumumab for 1 patient. ORR was 40% (10 patients) and DCR was 80% (20 patients). Median PFS and OS were 4.8 months (95% CI, 4.01-7.95) and 10.1 months (95% CI, 7.75-NR). DCR amongst patients with previous primary resistance to anti-EGFR (N = 7) was 100%. Two patients discontinued B + E due to drug-related adverse event. CONCLUSIONS: Though in a limited retrospective series of patients, these results show the efficacy of the combination of anti-BRAF and anti-EGFRs in BRAFm mCRC patients previously treated with an anti-EGFR. The use of this combination should thus not be ruled out in this population with limited therapeutic options.

Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study.

BACKGROUND: The anti-VEGF antibody bevacizumab associated with an irinotecan or oxaliplatin-based chemotherapy was proved to be superior to the chemotherapy alone in first or second line treatment of metastatic colorectal cancer (mCRC). However, it was reported to have no efficacy in 3rd or later-line, alone or with 5FU. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin. METHODS: Thirty one consecutive patients treated between May 2005 and October 2006 were included in this retrospective study. All of them have progressed under a chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin and received bevacizumab (5 mg/kg) in combination with FOLFIRI or simplified FOLFOX4 every 14 days. RESULTS: Ten patients (32.2%) had an objective response (1 CR, 9 PR) and 12 (38.8%) were stabilized. The response and disease control rates were 45.4% and 100% when bevacizumab was administered in 2nd or 3rd line and 25% and 55% in 4th or later line respectively (p = 0.024 and p = 0.008). Among the patients who had previously received the same chemotherapy than that associated with bevacizumab (n = 28) the overall response rate was 35.7% and 39.3% were stabilized. Median progression free survival (PFS) and overall survival (OS) were of 9.7 and 18.4 months respectively. Except a patient who presented a hypertension associated reversible posterior leukoencephalopathy syndrome, tolerance of bevacizumab was acceptable. A rectal bleeding occurred in one patient, an epistaxis in five. Grade 1/2 hypertension occurred in five patients. CONCLUSION: This study suggests that bevacizumab combined with FOLFOX or FOLFIRI may have the possibility to be active in chemorefractory and selected mCRC patients who did not receive it previously.

[Conservative treatment undifferentiated neuroendocrine tumors of the anal canal: two cases]. / Traitement conservateur des tumeurs endocrines peu différenciées du canal anal.

Undifferentiated neuroendocrine tumors are rare, and are characteristically aggressive with a poor prognosis. Most patients have metastatic disease at diagnosis, and cannot undergo curative surgical treatment. A chemotherapy regimen combining etoposide plus cisplatin is currently considered to be the reference treatment. We report two cases of poorly differentiated neuroendocrine tumors localized in the anal canal and treated by chemotherapy and radiotherapy resulting in prolonged complete local remission and preventing extended surgical excision.

Chemotherapy as initial treatment of locally advanced unresectable pancreatic cancer: a valid option?

INTRODUCTION: Radio-chemotherapy is the standard treatment for locally advanced unresectable pancreatic cancer (LAPC). Chemotherapy has been shown to be effective in the treatment of metastatic disease and we therefore evaluated its use as a first-line treatment for LAPC. PATIENTS AND METHODS: We carried out a retrospective analysis of all consecutive patients treated for LAPC (N=33) between July 1997 and April 2005, analysing the results of first-line chemotherapy (CT group) and radio-chemotherapy (RCT group) in this setting. RESULTS: The first-line treatment was RCT in six patients (18.3%) and CT in 26 patients (78.8%). Secondary treatment was administered to nine patients of CT group with well-controlled disease: "closure" radio-chemotherapy for seven patients (26.9%) and secondary resection for three (12%). After a median follow-up of 27 months, 23 patients died (69.7%). Overall survival was 13.8 months [95% CI: 10.1-19.4] for the whole population, 9.5 months [95% CI: 4.6-] for the RCT and 18.0 months [95% CI: 12.4-25.5] for the CT. Overall survival for the CT patients undergoing secondary surgery or "consolidation" radio-chemotherapy was 28.8 months [95% CI: 13.8-]. CONCLUSION: First-line chemotherapy is a valid option for LAPC treatment, making it possible to identify the patients who may benefit from secondary resection or radio-chemotherapy.

Risk of venous thrombosis in patients with pancreatic adenocarcinoma.

AIM: To estimate the risk of venous thrombosis associated with pancreatic adenocarcinoma and its consequences on treatment and survival. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 90 patients (49 males, 41 females - median age: 67 years [range: 37-94]). Pancreatic adenocarcinoma was histologically proved in 72 patients (81%) and was metastatic in 49 patients (54.4%). A venous thrombosis was observed in 24 patients (26.7%). A pulmonary embolism occurred in 4 patients with 2 deaths. The risk of venous thrombosis was significantly reduced by the use of anti-thrombotic prophylaxis (HR: 0.03 [95CI: 0.003-0.27]) and increased among patients with a biological inflammatory syndrome (HR: 9.0 [95CI: 2.30-34.4]) and metastatic disease (HR: 4.4 [95CI: 1.1-17.9]). Overall survival was not different between patients with (6.6 months) or without (6.1 months) venous thrombosis. CONCLUSION: The risk of venous thrombosis is important and may delay the treatment in patients with advanced pancreatic carcinoma. Some patients with high risk of venous thrombosis may benefit from a prophylactic anticoagulant treatment.

[Ovarian adenocarcinoma, primary or metastasic tumour of an adenocarcinoma of the colon: the role of molecular biology]. / Adénocarcinome ovarien, tumeur primitive ou métastase d'un adénocarcinome colique: apport de la biologie moléculaire.

After the primary diagnosis of an adenocarcinoma, diagnosis of the origin of a second adenocarcinoma is a problem (primitive or metastatic). Although the clinical evolution or location sometimes makes it possible to determine the origin of the new lesion, in some cases the diagnosis cannot be confirmed. Although a pathological examination is essential for diagnosis, it may still be inconclusive, making management difficult. The use of molecular biology can help solve this problem. We report the case of a patient who presented with an ovarian adenocarcinoma of an undetermined origin one year after an adenocarcinoma of the colon. This clinical case illustrates the contribution of molecular biology in the diagnosis of the origin of an ovarian adenocarcinoma by characterizing allelic losses in 5 chromosome segments using microsatellite markers genotyping in the two lesions. The comparative analysis suggested the primitive origin of the ovarian lesion.

[5-FU, folinic acid and cisplatin (LV5FU2-P) for unresectable pancreatic cancer]. / Chimiothérapie des adénocarcinomes du pancréas non résécables par 5-fluorouracile, acide folinique et cisplatine (LV5FU2-P).

AIM: To prospectively evaluate efficacy and tolerance of the 5-fluorouracil + folinic acid + cisplatin (LV5FU2-P) combination in the treatment of unresectable pancreatic carcinoma. PATIENTS AND METHODS: Between March 1998 and June 2000, 35 patients, mean age 61 years (37-75), with advanced (n=2) or metastatic (n=33) pancreatic cancer and initial performance status (WHO) of 0 (n=9), 1 (n=14) or 2 (n=12) were enrolled in the study. Two consecutive groups of patients were treated twice monthly, the first group (n=19) received the LV5FU2 regimen: a 2 hour-infusion of leucovorin 200 mg/m(2), 5-FU bolus 400 mg/m(2), followed by 22-hour continuous infusion of 5-FU 600 mg/m(2) on 2 consecutive days and cisplatin 50 mg/m(2) on day 2. The second group (n=16) received a simplified schedule with bolus leucovorin 40 mg/m(2), 5-FU bolus 400 mg/m(2) on day 1, followed by 5-FU 2400 mg/m(2) 48-hour infusion and cisplatin 50 mg/m(2) on day 2. Clinical symptoms and performance status were monitored together with weight changes. Tumor assessment was performed every 2 months. RESULTS: Three patients (9%) exhibited grade 4 neutropenia and grade 3 toxicity occurred in 31% of the patients (neutropenia: n=3, thrombocytopenia: n=1, vomiting: n=3, mucositis: n=3, diarrhea: n=1). There were no treatment-related deaths. Objective response was observed in 10 patients (29%, 95% confidence interval: 20-40%) including one complete response. Median progression-free survival and overall survival were 4.5 and 9 months, respectively. Six-months and 1-year survival rates were 70% and 25%, respectively. Weight gain was observed in 40% of the patients and performance status improved in 50%. CONCLUSION: LV5FU2-P regimen is active and well tolerated. It should be compared to gemcitabine as a first line therapy in advanced and metastatic pancreatic cancer.

[Chemotherapy with curative intent before (neoadjuvant) or after (adjuvant) surgery for colorectal cancer liver metastases]. / La chimiothérapie à visée curative avant (neoadjuvante), ou aprés (adjuvante) la chirurgie des métastases hépatiques des cancers colo-rectaux.

The 5-year risk of progression after complete resection of liver metastases is of 50% to 75%. Trials which have evaluated adjuvant systemic chemotherapy using 5FU--folinic acid, sometimes in association with intra-arterial chemotherapy, are not powerful and did not demonstrate a clear survival benefit. It is strongly recommended to participate to clinical trials. An adjuvant chemotherapy with the LV5FU2 regimen during 6 months is a reasonable option if the patient has not been included in a trial (professional agreement). A preoperative chemotherapy is not recommended if liver metastases are considered as right away resectable but it should be discussed if resectability is uncertain and/or in case of pejorative factors (professional agreement). If metastases resection has been facilitated or made possible by pre-operative chemotherapy, post-operative resumption of this chemotherapy should also been discussed (professional agreement).

Management of patients over 80 years of age treated with resection for localised colon cancer: results from a French referral centre.

BACKGROUND: Few data are available on management of very elderly colon cancer patients, especially concerning the parameters of therapeutic decisions and the role of geriatricians. METHODS: We retrospectively reviewed the charts of patients over 80 years of age who underwent surgery for a localised colon cancer in a French academic hospital. RESULTS: A total of 176 patients underwent surgery (postoperative morbidity and mortality rates: 25% and 6.7%). Adjuvant chemotherapy was discussed at a multidisciplinary team meeting for 91% of stage III patients, but only 13.5% of them were treated. Twenty-five patients relapsed: 19 were discussed at the multidisciplinary meeting and 16 were treated (5 had a metastasectomy). Despite their increase with time, geriatric assessments were infrequent, 17% (33% after 2006), and had no impact on postoperative morbi-mortality. Median overall survival and recurrence-free survival were 65.3 months and 65.1 months, respectively. Age, emergency surgery, and Charlson comorbidity index were independent prognostic factors. CONCLUSION: Selected elderly colon cancer patients have significant access to surgery. However, postoperative morbi-mortality rates remain high and adjuvant chemotherapy rarely prescribed. Perioperative geriatric assessment, especially before surgery, should be routinely proposed to these patients to evaluate its impact on postoperative morbi-mortality and prescription of adjuvant treatment.

Chemosensitivity in ovarian metastases from gastric cancer: a case series.

The development of ovarian metastases from gastric cancer indicates a turning point of the disease progression and is usually associated with poor prognosis. Efficacy of modern chemotherapy protocols in ovarian metastases from gastric cancer is unknown. In this case series, we have evaluated the chemosensitivity of ovarian metastases from gastric cancer in eight consecutive patients treated in our institution between January 2000 and April 2012. Median age at gastric cancer diagnosis was 48.3 years and ovarian metastases were mainly metachronous (88%). Patients were treated with FOLFOX or FOLFIRI protocols in first-line and with EOX protocol in second-line chemotherapy. These protocols of chemotherapy used in first- and second-line treatment were able to control the disease in 33.3% for ovarian metastases compared to 66.7% for extraovarian metastases. Mean overall survival (OS) from ovarian metastases diagnosis was 14.2 months. The four patients treated by bilateral oophorectomy had a longer mean OS (16 months) than the four patients who did not experienced surgery (12.3 months). In conclusion, this case series suggests that ovarian metastases from gastric cancer are less sensitive than extraovarian metastases to modern protocol of chemotherapy. To confirm these observations, a large retrospective study is ongoing.