Yves Becouarn

Oxaliplatin: available data in non-colorectal gastrointestinal malignancies

Oxaliplatin is a third-generation platinum compound which has proven its efficacy alone or in combination with 5-fluorouracil (5-FU) and/or new anticancer drugs in advanced colorectal cancer. Compared to the amount of available data in this cancer, little is known about the use of oxaliplatin in non-colorectal gastrointestinal malignancies. (1) The preclinical activity of the drug alone or in combination; (2) the phase I studies (oxaliplatin alone or in combination with irinotecan, raltitrexed, gemcitabine, folinic acid and 5-FU); (3) the phase II studies developed in gastric, pancreatic, biliary tract, hepatocellular carcinoma and malignant mesothelioma; and (4) some of the ongoing trials with regard to non-colorectal gastrointestinal malignancies are reviewed in this paper. To date, oxaliplatin appears as a real candidate for clinical development in this field.

Cancer chemotherapy in the elderly: a series of 51 patients aged>70 years

SummaryA total of 2,238 new cancer patients were treated in our institution in 1988; among the 423 (18.9%) who were>70 years old, 51 underwent chemotherapy. The median age was 75.8 years, and the Karnofsky performance status (KPS) was ≥70% for 40 patients. Malignancies were hematopoietic in 24 cases (47%) and digestive in 15 patients (29%), and 12 subjects (24%) had other types of cancers. The first chemotherapy course was given at the full dose to 23/51 (45.1%) patients. The drug dose was reduced for 28/51 (54.9%) patients, due in 25 cases to the subjects being>70 years old. Neither age, KPS, pretreatment assessment, nor cancer extent was correlated with the modifications made to the first cycle. An overall toxicity of grade 3+4 (WHO grading scale) was noted in 10 subjects (19.6%). Although these elderly patients were probably selected, analysis of their charts did not evidence an increase in chemotherapy toxicity, regardless of the dose they received.

Improved control of cisplatin-induced emesis with a combination of high doses of methylprednisolone and metoclopramide: a single-blind randomized trial

Forty-seven patients undergoing their first course of chemotherapy containing cisplatin in combination with other drugs were randomized to compare the antiemetic efficacy of high dose metoclopramide vs. high dose methylprednisolone added to metoclopramide. The number of patients who experienced no emetic episodes was significantly higher with the combination regimen (P less than 0.01). In addition, both the mean number of emetic episodes (P = 0.01) and the duration of nauseas (P = 0.025) were decreased with the combination regimen. Both antiemetic regimens were well tolerated. Sex affected the response, with women having more nausea and vomiting than did men (P less than 0.05).

A survey in general practice about undergraduate cancer education: results from Gironde (France).

In Bordeaux University (France), oncology teaching was individualized in 1972, and an optional oncology course devoted to general practice was created in 1980. To evaluate the adequacy of these two oncology classes for general practitioners and so to adapt our current teaching, we sent to each of 1,219 general practitioners (GPs) of Gironde (county of the southwest of France) an anonymous questionnaire about oncology teaching in prevention, screening and cancer detection, cancer management, and curriculum balance. We received 688 (56.4%) responses. GPs said that as undergraduates, they were insufficiently instructed about screening programs (65%), pain control (80%), palliative care (50%) and fundamental or biological data (greater than 55%). This situation, which showed signs of improvement from 1975 on, has improved even more since 1985. General practitioners, as well as undergraduates, are not yet adequately educated about cancer for general practice, so we have to adapt better our current teaching for undergraduates and those in continuing medical education.

Evaluation of efficacy and safety of FOLFIRI for elderly patients with gastric cancer: A first-line phase II study

OBJECTIVE Current chemotherapy protocols for gastric cancer present high toxicity. The FOLFIRI regimen has shown promising results with elderly colorectal cancer patients and for gastric cancer patients but this is the first report on elderly gastric cancer patients. DESIGN In this multicenter non-randomized phase II trial, we administered the FOLFIRI chemotherapy protocol (irinotecan [180 mg/m(2)], fluorouracil [5-FU] [400 mg/m(2)] and folinic acid 400 mg/m(2) or 200mg/m(2) of l-folinic acid) to patients aged over 70 years with locally-advanced or metastatic gastric cancer combined with Comprehensive Geriatric Assessment (CGA). Responses were assessed at 2 months. RESULTS Forty-two patients received eight cycles of the FOLFIRI regimen, with 82.5% of patients showing disease control: 10 patients (26%) showing objective (partial or complete) responses and 23 (57.5%) showing stable disease. One-year overall survival (OS) was 41.5% [95%CI 26.5-56.0] and one-year progression-free survival (PFS) was 31.8% [95%CI 18.4-46.1%]. We observed 10 Grade 3/4 hematologic toxicities with one febrile neutropenia. CGA data demonstrated that geriatric functions were not altered by treatment and that nutritional status improved over treatment. CONCLUSIONS Results show excellent disease control and relatively high survival rates with limited toxicity similar to younger patients indicating that this regimen should be considered as a possible treatment in advanced gastric cancer of the elderly.

COLONIC METASTASIS OF A RENAL CARCINOMA. A CASE REPORT

A 64 year-old man with a metastatic clear-cell renal carcinoma experienced low intestinal bleeding. The endoscopy revealed a polypoid mass in the left colon which proved to be a metastasis of the renal carcinoma. This is an uncommon cause of intestinal hemorrhage, and a rare localization of metastatic deposits.

Phase II study of a 5-fluorouracil, teniposide and mitomycin-C combination chemotherapy in advanced colorectal carcinomas.

Fifteen patients (median age 62, with a mean Karnofsky performance status of 70%) presenting with advanced colorectal carcinoma were included in the study. The treatment combination consisted of 5-fluorouracil (800 mg/m2 in a 30 min infusion, days 1 and 8), teniposide (80 mg/m2 in i.v. push, day 1), and mitomycin-C (10 mg/m2 in i.v. push, day 1); therapy was resumed every 29 days. A partial objective response (for 4 months) was noted in one patient who had received no prior chemotherapy; the overall median survival of the 15 patients was 5 months. Toxicity was acceptable, with leukopenia (1 case), mucositis (1 case) and diarrhea (1 case), leading to drug dose reduction. Chemotherapy was stopped once owing to severe hematologic toxicity. With the doses and schedule used, the drug combination appears to have minimal activity in advanced colorectal cancer.

Cancer of the pancreas

Only exocrine pancreas cancer (ductal adenocarcinoma) is treated herein, excluding other malignant tumors of the pancreas, notably ampullomas, endocrines tumors, and cystadenocarcinomas, which pose different problems. This work is based on “Les standards, options et recommandations de la Fédération Nationale des Centres de Lutte Contre le Cancer” [1], the recommendations (internal publications) of the Fédération Francophone de Cancérologie Digestive (FFCD) [2] and the GERCOR (Groupe d’Etude et de Recherche Clinique en Oncologie Radiothérapie), and their updates (Medline, January 1999 to January 2005).

Small bowel adenocarcinoma: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)

BACKGROUND This document is a summary of the French intergroup guidelines regarding the management of small bowel adenocarcinoma published in October 2016. METHOD This collaborative work, co-directed by most French Medical Societies, summarizes clinical practice recommendations (guidelines) on the management of small bowel adenocarcinoma. Given the lack of specific data in the literature, all references are given by analogy with colon cancer. The classification used is the AJCC (American Joint Committee on Cancer) pTNM classification (7th edition 2009). RESULTS Small bowel adenocarcinoma has a poor prognosis; less than 30% of patients survive for 5 years after the (first) diagnosis (5-year survival of less than 30%). Due to the rarity of the disease and the retrospective data, most recommendations are based on expert agreement. The initial evaluation is based on chest-abdomen-pelvis CT scan, CEA assay, GI endoscopy and colonoscopy in order detect lesions associated with a predisposing disease. Surgical treatment is currently the only curative option for stage I and II. Adjuvant chemotherapy can be discussed for Stage III and Stage II with T4 (expert agreement). With regard to metastatic tumors, treatment with fluoropyrimidine combined with platinum salts should be considered (expert agreement). CONCLUSION Few specific data exist in the literature on this type of tumor; most of the recommendations come from expert agreements or by analogy with colon cancer. Thus, each case must be discussed within a multidisciplinary team.

Toxicité hépatique des inhibiteurs des tyrosines kinases : mécanismes en cause et conséquences pratiques

Tyrosine kinase inhibitors (TKIs) are used for the targeted treatment of solid cancers. TKIs produce a variable incidence of liver adverse events (5-25%) which can progress to severe liver injury in a minority of patients if treatment is maintained despite ongoing injury. This risk requires careful patient management to maintain treatment benefit without harm. This review highlights the various mechanisms of idiosyncratic hepatotoxicity, the formation of reactive metabolites and how this leads to toxicity. These critical events depend of the drug-specific characteristics of each TKI and the patient risk factors, especially genetic characterization. With improved understanding of the mechanisms leading to hepatotoxicity, several strategies have been adopted to prevent or treat this side effect. Recommendations on liver function liver test monitoring have been proposed according to each TKI.