Philippe Lasser

Perioperative Chemotherapy Compared With Surgery Alone for Resectable Gastroesophageal Adenocarcinoma: An FNCLCC and FFCD Multicenter Phase III Trial

PURPOSE After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma. PATIENTS AND METHODS Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS. RESULTS Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio [HR] for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups. CONCLUSION In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.

Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin

SummaryThe purpose of this study was to evaluate by a retrospective analysis of 53 patients the efficacy of chemotherapy combining etoposide and cisplatin in the treatment of neuroendocrine tumours. The regimen was a combination of etoposide 100 mg m–2 day–1 for 3 days and cisplatin 100 mg m–2 on day 1, given by 2-h intravenous infusion, administered every 21 days. Twelve patients had a well-differentiated and 41 a poorly differentiated neuroendocrine tumour. Toxicity of treatment was assessed in 50 patients and efficacy in 52 patients. Among the 11 patients with a well-differentiated tumour evaluable for tumoural response, only one (9.4%) had a partial response for 8.5 months. Forty-one patients with a poorly differentiated tumour showed an objective response rate of 41.5% (four complete and 13 partial responses); the median duration of response was 9.2 months, the median overall survival 15 months and the median progression-free survival 8.9 months. Haematological grade 3–4 toxicity was observed in 60% of the cases with one treatment-related death, digestive grade 3–4 toxicity in 40% and grade 3 alopecia was constant. No severe renal, hearing and neurological toxicities were observed (grade 1 in 6%, 14%, 72% respectively and no grade >1). We confirm that poorly differentiated neuroendocrine tumours are chemosensitive to the etoposide plus cisplatin combination. However, the prognosis remains poor with a 2-year survival lower than 20% confirming that new therapeutic strategies have to be developed.

Hepatic Arterial Oxaliplatin Infusion Plus Intravenous Chemotherapy in Colorectal Cancer With Inoperable Hepatic Metastases: A Trial of the Gastrointestinal Group of the Fédération Nationale des Centres de Lutte Contre le Cancer

PURPOSE Isolated hepatic metastases of colorectal cancer constitute a frequent and serious therapeutic problem that has led to the evaluation of hepatic arterial infusion (HAI) of different drugs. Oxaliplatin combined with fluorouracil (FU) and leucovorin is effective in the treatment of colorectal cancer. In this context, a phase II study was conducted to evaluate concomitant administration of oxaliplatin by HAI and intravenous (IV) FU plus leucovorin according to the LV5FU2 protocol (leucovorin 200 mg/m(2), FU 400 mg/m(2) IV bolus, FU 600 mg/m(2) 22-hour continuous infusion on days 1 and 2 every 2 weeks). PATIENTS AND METHODS Patients had metastatic colorectal cancer that was restricted to the liver and inoperable. The patients were not to have previously received oxaliplatin. After surgical insertion of a catheter in the hepatic artery, patients were treated with oxaliplatin 100 mg/m(2) HAI combined with FU + leucovorin IV according to the LV5FU2 protocol. Treatment was continued until disease progression or toxicity. Response was evaluated every 2 months. RESULTS Twenty-eight patients were included, and 26 patients were treated. Two hundred courses of therapy were administered, and the median number of courses received was eight courses (range, zero to 20 courses). The most frequent toxicity consisted of neutropenia. The main toxicity related to HAI was pain. The intent-to-treat objective response rate was 64% (95% CI, 44% to 81%; 18 of 28 patients). With a median follow-up of 23 months, the median overall and disease-free survival times were 27 and 27 months, respectively. CONCLUSION The combination of oxaliplatin HAI and FU + leucovorin according to the LV5FU2 protocol is feasible and effective in patients presenting with isolated hepatic metastases of colorectal cancer.

Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients

BACKGROUND Very few series have reported indications for and results of hepatectomy for isolated unique or multiple liver metastases (LM) from a noncolorectal primary. We performed a prospective analysis of 147 patients submitted to hepatectomy for LM to evaluate the results and indications for this unusual type of treatment. STUDY DESIGN Of 538 patients submitted to hepatectomy for a malignant tumor between 1984 and 1996, 147 underwent operations for noncolorectal LM. Conventional and unconventional hepatectomy procedures were used with intermittent clamping of the hepatic pedicle, and in some patients with intermittent vascular occlusion of the liver. RESULTS Postoperative hospital mortality was 2%. The crude 5-year survival was 36%, and survival without progressive disease was 28%. No difference was observed in survival when synchronous and metachronous LM were compared, or when patients with more or fewer than three LM were compared. Five-year survival rates were 20% for 35 breast cancers, 74% for 27 neuroendocrine tumors, 46% for 20 testicular tumors, 18% for 13 sarcomas, and slightly less than 20% for 11 gastric carcinomas, 10 melanomas, and 7 tumors of the gallbladder, according to the primary. Survival exceeded 20% for 6 gynecologic tumors but was disappointing for head and neck cancers, when the primary was unknown, or when the tumor was truly undifferentiated. CONCLUSIONS Certain guidelines emerge from this series on the indications and uses of adjuvant chemotherapy. Indications for hepatectomy are relatively straightforward for neuroendocrine, testicular, and renal tumors. Hepatectomy for LM from other primaries appears beneficial in certain sarcomas, breast and gynecologic cancers, and perhaps melanoma, for which selection criteria, unfortunately, remain obscure.

Treatment of peritoneal carcinomatosis from colorectal cancer: impact of complete cytoreductive surgery and difficulties in conducting randomized trials.

BackgroundColorectal peritoneal carcinomatosis (PC) is a frequent and very lethal event. However, cure may be possible with maximal cytoreductive surgery associated with early postoperative intraperitoneal chemotherapy (EPIC).MethodsBetween 1996 and 2000, we conducted a two-center prospective randomized trial comparing EPIC plus systemic chemotherapy with systemic chemotherapy alone, both after complete cytoreductive surgery of colorectal PC. Only 35 patients could be included among the 90 who were theoretically required, mainly because of patient dissatisfaction with the inclusion criteria. For this reason, the trial was stopped prematurely.ResultsAnalysis of these 35 patients showed that complete resection of PC resulted in a 2-year survival rate of 60%—far above the classic 10% survival rate among patients with colorectal PC treated with systemic chemotherapy and symptomatic surgery. In this small series, EPIC did not demonstrate any advantage for survival.ConclusionsThis supports the use of complete cytoreductive surgery in selected patients and calls for a prospective randomized trial comparing adjuvant systemic chemotherapy with intraperitoneal chemohyperthermia after complete resection.

Results of R0 Resection for Colorectal Liver Metastases Associated With Extrahepatic Disease

Background: Extrahepatic malignant disease has always been considered an absolute contraindication to hepatectomy for colorectal liver metastases. This study reports the long-term outcome and prognostic factors of patients undergoing extrahepatic disease resection simultaneously with hepatectomy for liver metastases.Methods: From January 1987 to January 2001, 75 patients underwent a complete R0 resection of extrahepatic disease simultaneously with hepatectomy for colorectal liver metastases. They were inscribed in a registry and then prospectively followed up. They represented 25% of the 294 patients who underwent an R0 hepatectomy for colorectal liver metastases during the same period.Results: The mortality rate was 2.7%, and morbidity was 25%. After a median follow-up of 4.9 years (range, 1.7–13.4 years), the overall 3- and 5-year survival rates were 45% and 28%, respectively. By using a Cox model, there was a significant difference in survival between patients with single versus multiple sites of extrahepatic disease. Also, the presence of more than five liver metastases was a significant parameter.Conclusions: Extrahepatic disease in colorectal cancer patients with liver metastases should no longer be considered as a contraindication to hepatectomy. However, this intended R0 resection cannot be performed in 50% of laparotomized patients, and negative prognostic factors for surgery include the presence of multiple extrahepatic disease sites or more than five liver metastases.

Results of 136 curative hepatectomies with a safety margin of less than 10 mm for colorectal metastases

It is now established that liver resection is beneficial for metastases from colorectal cancer. Nevertheless, a surgical margin estimated at less than 10 mm at preoperative imaging is considered an absolute contraindication to surgery by some, and a relative contraindication by others. The true impact of the width of the margin on the prognosis is unclear.

Local recurrences after intraoperative radiofrequency ablation of liver metastases: a comparative study with anatomic and wedge resections.

BackgroundThe indications and results of intraoperative radiofrequency ablation (RFA) of liver metastases (LMs) are not well defined in the literature and have never been compared with those of hepatectomy. The aim of the study was to appreciate the local recurrence rate of RFA in comparison with anatomic and wedge resection.MethodsEighty-eight patients with technically unresectable LMs were treated with curative intent. The LMs were treated by anatomic resection (40 patients, 213 LMs) when large, by wedge resection (64 patients, 99 LMs) when peripheral and small, and by RFA (88 patients, 227 LMs) when central and small. The median follow-up was 27.6 months (range, 15–74 months), and a total of 539 LMs were treated (median of 5 per patient).ResultsThe local recurrence rates were 5.7% for the 227 RFAs, 7.1% for the 99 wedge resections, and 12.5% for the 40 anatomic resections (P = .216). Local recurrence rates after RFA were correlated with LMs larger than 30 mm (P < .001) and with LMs in direct contact with large vessels (P < .001).ConclusionsRFA is as efficient and safe as wedge or anatomic resections in terms of local control.

Prognostic factors in primary gastrointestinal non-Hodgkin's lymphoma. A multivariate analysis, report of 106 cases, and review of the literature.

The authors have reviewed 106 cases of primary gastrointestinal non‐Hodgkins lymphoma (GI‐NHL) treated at the Institut Gustave‐Roussy (IGR), France, between 1975 and 1986. The occurrence was 55 in the stomach, 26 in the small intestine, ten ileocecal, seven in the large intestine, and eight patients had multiple involvement. Patients were clinically staged according to the Ann Arbor staging system using the modification of Musshoff for Stage IIE. All histologic material of the 106 patients were reviewed and graded according to the Working Formulation (WF) and the Kiel classifications. Most patients received combination chemotherapy as part or all of their primary treatment program (95 patients, 90%). Seventy five patients (71%) had a multimodality treatment. The overall 5‐year survival rate was 60%. Sixteen variables were tested by univariate analyses for prognostic influence on survival. Of these, only clinical stage (P < 0.001), the achievement of initial complete remission (CR) (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.01), mesenteric involvement (P = 0.03), and serosal infiltration (P = 0.05) were significant prognostic factors. Important variables were tested by a multivariate analysis using the Cox model taking into account different treatment modalities. Only three variables entered the regression analysis at a significant level: clinical stage (P = 0.02), surgical resection (P = 0.03), and histologic grade (Kiel) (P = 0.04). When the achievement of initial CR was introduced into the model, it was the most significant variable (P < 0.001) whereas all other variables became nonsignificant except for the histologic grade (Kiel) (P = 0.004). Based on results of the multivariate analyses we propose two prognostic classifications of patients: one at the initial evaluation depending on clinical stage, surgical resectability, and histologic grade (Kiel); the other at the end of primary treatment depending on the achievement or not of CR and the histologic grade.

Quality of Life of Patients Operated on for Low Rectal Cancer: Impact of the Type of Surgery and Patients’ Characteristics

PURPOSEThis study was designed to compare the impact of a permanent colostomy and sociodemographic characteristics on the quality of life of patients operated on for low rectal cancer.METHODSA cross-sectional study was performed by use of the European Organization for Research and Treatment of Cancer QLQ-C30 and CR-38 questionnaires. Patients came to the hospital to fill out the self-administered questionnaire or were sent the questionnaire by mail, followed by a live or telephone interview. All patients had undergone one of four operations: low anterior resection with colorectal or coloanal anastomosis (non-stoma group), or abdominoperineal resection with pseudocontinent perineal colostomy (nonstoma group) or left lower quadrant colostomy (stoma group).RESULTSA total of 132 patients were included for analysis and there were no missing data. For the majority of quality of life scores (26/29), there was no significant difference between stoma and nonstoma patients. However, stoma patients complained of diminished body image (P = 0.0022), and this was especially true for married (P = 0.0073) and less educated (P = 0.0014) patients at subgroup analysis. Stoma patients experienced greater financial worries (P = 0.0029), whereas nonstoma patients had greater gastrointestinal concerns (P = 0.0098).CONCLUSIONSAlthough most quality of life scores between stoma and nonstoma patients were similar, significant differences regarding body image, finance, and gastrointestinal symptoms, especially for married and less educated patients, were noticed. These factors should be taken into account, along with oncologic criteria, to better tailor treatments to patients.