Definitive chemoradiotherapy in patients with esophageal adenocarcinoma: an alternative to surgery?

BACKGROUND AND OBJECTIVES: Definitive chemoradiotherapy (CRT) is considered curative intent treatment for locally advanced esophageal squamous cell carcinoma. Data concerning the usefulness of definitive CRT in patients with esophageal adenocarcinoma (ADC) are lacking. The aim of the study was to compare the results of definitive CRT versus surgery in patients with an ADC. METHODS: All consecutive patients with a non-metastatic ADC treated between 1994 and 2008 were retrospectively assessed. Patients were divided into two groups: surgery group (±pre-operative treatment) versus definitive CRT group. RESULTS: In surgery and definitive CRT groups, 67 and 79 patients were evaluated, respectively. A complete resection was achieved in 92.5% of patients in surgery group and a clinical complete response was observed in 49.4% of patients in definitive CRT group. Overall survival was 36.2 ± 2.0 months in surgery group versus 16.5 ± 0.8 months in definitive CRT group (P = 0.02). The predictive factors of survival were age (P < 0.01), stage (P = 0.04), WHO performance status (P < 0.01), initial weight loss (P < 0.01), and the treatment group (P < 0.01). CONCLUSIONS: The results of the study do not support definitive CRT as an alternative to surgery in esophageal ADC treatment. Definitive CRT should be reserved for patients with a major operative risk.

Control of pelvic symptoms in patients with rectal cancer and synchronous metastases.

OBJECTIVE: The optimal treatment strategy for rectal cancer (RC) with synchronous metastases remains an issue of debate. The aim of this study was to evaluate the impact of surgery and radiation on the control of pelvic symptoms in this setting. METHODS: Consecutive patients with RC and synchronous metastases were retrospectively assessed and divided into four treatment groups: surgical resection of rectal tumor (S); radiotherapy with/without chemotherapy followed by surgery (CRTS); chemoradiotherapy (CRT); and chemotherapy only (CT). Each group was evaluated in terms of duration of pelvic symptom-free periods (relative to overall survival). RESULTS: A total of 96 patients were evaluated: S: n=30; CRTS: n=21; CRT: n=27; and CT: n=18. After treatment, pelvic symptoms persisted in 14.7% patients (S=0%, CRTS=7.1%, CRT=31.8%, CT=25%; P=0.01). The relative pelvic symptom-free periods were 93.0% in the S group, 83.1% in the CRTS group, 53.0% in the CRT group and 53.2% in the CT group (P<0.01). On multivariate analysis, only surgical treatment correlated with a significant relative pelvic symptom-free period (P<0.01), with an adjusted hazards ratio of 2.80 [95% CI: 1.79-4.39]. CONCLUSION: Our results suggest that rectal resection was the most effective therapeutic procedure in selected patients with RC and synchronous metastases, offering the patients the longest pelvic symptom-free periods.

Safety and outcome of definitive chemoradiotherapy in elderly patients with oesophageal cancer.

Little is known about chemoradiotherapy (CRT) in elderly patients with a locally advanced oesophageal cancer (OC). The aim of our study was to evaluate the tolerance and the outcome of elderly patients older than 70 years treated with CRT for a non-metastatic OC. Chemoradiotherapy was based on radiotherapy combined with a cisplatin-based chemotherapy. Clinical complete response (CCR) to CRT was evaluated on upper digestive endoscopy and computed tomography scan 6-8 weeks after CRT completion. One hundred and nine consecutive patients were included. A CCR was observed in 63 patients (57.8%) and 2-year survival was 35.5%. Adverse events > or =grade 3 were observed in 26 (23.8%) patients. Chemotherapy dose reduction, chemotherapy delays more than 1 week, and treatment discontinuation were observed in 33 (30.3%), 45 (41.3%), and 17 patients (15.6%), respectively. Comorbidity index according to Charlson score was significantly associated with treatment tolerance. In multivariate analysis, a CCR to CRT (P<0.01), a dose of radiotherapy > or =80% (P=0.02), and a Charlson score < or =2 (P=0.046) were identified as independent prognostic factors of overall survival. These results suggest that CRT could be considered as an effective treatment without major toxicity in elderly patients with OC.

Prior chemoradiotherapy is associated with a higher life-threatening complication rate after palliative insertion of metal stents in patients with oesophageal cancer.

BACKGROUND: Self-expanding metal stents are used routinely to palliate dysphagia due to oesophageal cancer. STUDY AIM: To compare the frequency of life-threatening complications after self-expanding metal stent insertion, depending on whether patients received prior chemoradiotherapy or no treatment. PATIENTS AND METHODS: During 7 years, 116 consecutive patients were treated at a single centre in a palliative intent by insertion of self-expanding metal stent for dysphagia due to an oesophageal cancer. Patients were retrospectively separated into two groups: patients with chemoradiotherapy before self-expanding metal stent insertion (group 1, n = 56) and patients with no treatment before or after self-expanding metal stent insertion (group 2, n = 60). Life-threatening complications were compared and predictive risk factors of postprocedure complications were identified. RESULTS: Median dysphagia was significantly improved during the first month (grade 3 to grade 1 in the two groups). Early and late major complications occurred more frequently in group 1 (23.2% vs. 3.3%; P < 0.002 and 21.6% vs. 5.1%; P < 0.02 respectively). Prior chemoradiotherapy was the only independent predictive factor of postprocedure major complications, with an odds ratio of 5.59 (CI 95% 1.7-18.1). CONCLUSIONS: Life-threatening complications after palliative self-expanding metal stent placement seem to occur more frequently in patients with prior chemoradiotherapy. Prevention of these severe complications should be considered before stenting.

Identification of novel germline hMLH1 mutations including a 22 kb Alu-mediated deletion in patients with familial colorectal cancer.

We analyzed the hMLH1 gene in 17 unrelated families with putative hereditary nonpolyposis colorectal cancer. The complete hMLH1 cDNA was amplified in one step, and after a second amplification, four overlapping segments were directly sequenced. We detected, in five families that did not meet the complete Amsterdam criteria, five alterations, including a double-base change resulting in a missense mutation (Lys-618-Ala), a splicing mutation affecting the intron 4 splice acceptor site, a 2-bp deletion at codon 726, a 7-bp deletion at codon 626, and a deletion of exons 13-16. The latter alteration was shown to result from a 22-kb genomic deletion due to a homologous recombination between Alu repeats located in introns 12 and 16. The detection of five germline hMLH1 mutations in five families that only partially fulfilled the Amsterdam criteria shows that these criteria do not allow the identification of all familial colorectal cancers due to mutations of the mismatch repair genes. The numerous Alu repeats present within the hMLH1 gene and the observation of large genomic deletions suggest that (a) Alu-mediated deletions might frequently be involved in hMLH1 inactivation, and (b) reverse transcription-PCR analysis, which allows the amplification of the entire coding region of the hMLH1 gene in one step, might be the most appropriate method for the detection of hMLH1 alterations.

Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial.

PURPOSE: The aim of the study was to evaluate the efficacy of antiandrogen therapy on overall survival and response in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial. According to a two-by-two factorial design, patients were randomly assigned to receive one of the following treatments: pure antiandrogen plus placebo (A+P group, 60 patients); luteinizing hormone-releasing hormone (LHRH) agonist plus placebo (LHRH+P group, 62 patients); pure antiandrogen plus LHRH agonist (A+LHRH group, 62 patients); or placebo plus placebo (P+P group, 60 patients). Pure antiandrogen consisted of Anandron (Roussel-Uclaf Laboratory, Romainville, France) administered orally (300 mg daily for 1 month, then 150 mg daily). LHRH consisted of goseriline acetate (3.6 mg) or triptoreline (3.75 mg) administered monthly by subcutaneous injection. Treatment was given until death. Response was evaluated every 8 weeks according to World Health Organization (WHO) criteria. RESULTS: Six patients were considered ineligible. One patient had a complete response (A+P arm) and three had a partial response (two in the LHRH+P arm and one in the A+LHRH arm). An overall log-rank test did not demonstrate any significant difference in survival among the four arms. Taking the factorial design into account, comparison of survival showed no significant difference between Anandron-containing regimens and others, or between LHRH-containing regimens and others. No serious side effects occurred for any regimen. CONCLUSION: This controlled study shows clearly the lack of efficacy of androgen treatment in unresectable HCC.

Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

PURPOSE: To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS: A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS: Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION: This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group.

PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.

Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group.

PURPOSE: To compare the efficacy and tolerability of etoposide, leucovorin, and bolus fluorouracil (ELF) or infusional fluorouracil plus cisplatin (FUP) with that of the reference protocol of fluorouracil, doxorubicin, and methotrexate (FAMTX) in advanced gastric cancer. PATIENTS AND METHODS: A total of 399 patients with advanced adenocarcinoma of the stomach were randomized and analyzed for toxicity, tumor response, and progression-free and overall survival. Only reviewed and confirmed responses were considered. The analysis of remission was based on assessable patients with documented measurable lesions. The intent-to-treat principle, log-rank test, and Cox regression model were used for the statistical analysis of time-to-event end points. RESULTS: The overall response rate for 245 eligible patients with measurable disease was 9% with ELF, 20% with FUP, and 12% with FAMTX, with no significant differences. One hundred twelve patients were eligible for efficacy in assessable, nonmeasurable disease. No change was observed in 66% of patients treated with ELF, 56% with FUP, and 55% with FAMTX. Two patients achieved a complete tumor regression (one each for ELF and FAMTX). With a median follow-up time of 4.5 years, the median survival times were 7.2 months with ELF, 7.2 months with FUP, and 6.7 months with FAMTX, respectively, with no significant differences. Nonhematologic and hematologic toxicities of ELF, FUP, and FAMTX were acceptable, with neutropenia being the major toxicity for all three regimens. Seven treatment-related deaths occurred (two with FUP and five with FAMTX). CONCLUSION: All three investigated regimens demonstrate modest clinical efficacy and should not be regarded as standard treatment for advanced gastric cancer. New strategies should be considered to achieve a better clinical efficacy in the treatment of advanced gastric cancer.

Fotemustine in patients with advanced gastric cancer, a phase II trial from the EORTC-GITCCG (European Organization for Research and Treatment of Cancer, Gastrointestinal Tract Cancer Cooperative Group).

Fotemustine activity was evaluated in 26 patients, mostly pretreated, with advanced gastric cancer. Its main toxicity was haematological with grade 3-4 neutropenia in 32% and grade 3-4 thrombocytopenia in 50% of the patients, complicated by 2 toxicity-related deaths due to haemorrhage. No complete or partial responses were observed in the 26 eligible patients and median survival was only 11 weeks. Fotemustine therefore has no activity in advanced gastric cancer.

Prospective randomised study of split-course radiotherapy versus cisplatin plus split-course radiotherapy in inoperable squamous cell carcinoma of the oesophagus.

Between 1983 and 1989, 211 patients with inoperable squamous cell carcinoma of the oesophagus were randomised in a study comparing split-course irradiation (two courses of 20 Gy in five fractions of 4 Gy, separated by a rest of 2 weeks) (arm A) and the same split-course irradiation in combination with cisplatin (CDDP) (3-4 days before each of the two courses of radiotherapy, repeated every 3-4 weeks, for a total of six cycles) (arm B). The Cox's regression model with retrospective stratification was used to compare the two arms to correct for the imbalance at randomisation of the T classification. The median overall survival was 7.9 (95% confidence interval (CI) 7.3-9.4) months in arm A and 9.6 (95% CI 8-13.5) months in arm B. The difference in overall survival was only borderline significant (P=0.048) with a reduction of the instantaneous rate of death of 24%. The 1 and 2 year overall survival rate were respectively 29% (95% CI 21-37%) and 15% (95% CI 8-22%) in arm A and 45% (95% CI 36-54%) and 20% (95% CI 13-27%) in arm B; thereafter, the survival curves became similar. The median progression free survival (PFS) was 5.0 (95% CI 4.6-5.7) versus 6.9 (95% CI 5.3-8.7) months (P=0.028) and the median time to local progression was 6.2 (95% CI 5.1-7.6) months versus 10.9 (95% CI 8.1-15.5) months (P=0.018), respectively, in arms A and B. Haematological toxicities were slightly more commonly observed in the combined group (1% versus 6%). This study shows that split-course irradiation in combination with CDDP is very well tolerated and should be preferred to radiotherapy alone.

5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration. Final results of a randomised trial in metastatic colorectal cancer.

The aim of this Phase III, balanced randomised trial was to compare continuous intravenous infusion (CVI) of 5-FU with bolus (B) administration for metastatic colorectal cancer (CRC). One hundred and fifty-five non-pretreated patients were randomised to receive CVI 5-FU at a dose of 750 mg/m2/day (d), 7 d every 21 d (n = 77), or bolus 5-FU 500 mg/m2/d x 5 d every 28 d (n = 78). Incremental dose escalation at 50 mg per step was recommended in the absence of toxicity. All the patients had measurable metastatic disease (M), particularly, liver and a good performance status (WHO grade 0-1). Dose intensity was significantly higher in CVI than in the bolus group: 1369 mg/m2/week versus 558 mg/m2/week (P = 0.0001). Grade II-IV stomatitis was more frequent in the CVI group (31% versus 9%; P < 0.0001) as was hand and foot syndrome (14% versus 3%; P < 0.001). Diarrhoea (22% versus 12%) and grade III granulocytopenia (2% versus 6%) were comparable. Responses were more frequent in the CVI (26%) than in the bolus group (13%) (P < 0.04); progression-free survival was higher for the CVI group (P = 0.04), but there was no statistical difference in overall survival (median: 10 months (m) compared to 9 m), and 1 year survival (SD) 42% (6%) versus 40% (6%). In the multivariate analysis, survival was better for patients with a good PS, well-differentiated adenocarcinomas and a primary tumour without serosal extension. In conclusion, with a higher dose intensity, CVI 5-FU improved tumour control, but not overall survival.

Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer.

Patients with measurable or evaluable locally advanced or metastatic squamous cell carcinoma of the oesophagus were treated with cisplatin (CDDP), 100 mg/m2, combined with 5-fluorouracil (5-FU) at a dose of 1000 mg/m2 as a continuous infusion from days 1-5 (Arm A) or with CDDP alone (Arm B). Cycles were repeated every 3 weeks. 92 patients were randomised centrally, 88 were eligible. The response rate was 35% (95% CI (confidence interval), 20-54%) in Arm A and 19% (95% CI, 8-35%) in Arm B. One complete response was observed in each arm. The median duration of survival was 33 weeks and 28 weeks for Arm A and Arm B, respectively. Haematological and non-haematological toxicities were more frequent and more severe in Arm A. The most prominent toxicities were grade 4 aplasia and septicaemia (2), meningeal haemorrhage (1), cerebrovascular accident (3) and ischaemia of the lower limbs (1) all occurring in Arm A. Overall, seven treatment-related deaths (16%) were observed in Arm A, none in Arm B. The severe side-effects induced by the combination suggest that, currently, no standard chemotherapy can be recommended for patients with advanced squamous cell oesophageal cancer.

Palliative therapy of inoperable oesophageal carcinoma with radiotherapy and methotrexate: final results of a controlled clinical trial.

Between May 1976 and January 1982, 170 patients were entered in a randomized study comparing a combined treatment consisting of methotrexate followed by irradiation versus radiotherapy alone in patients with non metastatic inoperable oesophageal cancer. Methotrexate was administered subcutaneously in 4 days to a total dose of 24 mg/m2. Radiotherapy was performed, in both groups, at a dose of 56.25 Gy in 25 fractions (5 weeks). The administration of methotrexate did not lead to an increased intolerance to radiotherapy but severe hematological toxicities were observed in 7.8% of the cases. No difference in the duration of survival was detected. Initial performance status of the patients and their weight loss prior to entry on trial were the factors that were most predictive of the patient's prognosis.

Pre-operative kinetic parameter determination of colorectal adenocarcinomas. Prognostic significance.

BACKGROUND: The aim of this study was to test the prognostic value of pre-operative assessment of tumour kinetics in colorectal adenocarcinoma. METHODS: The study of tumour kinetics was performed using an in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed using flow cytometry. This procedure enables calculation of the in vivo S-phase fraction labelling index (LI), the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). Disease-free survival curves were calculated by a Kaplan-Meier method. The statistical significance between curves was tested by the log rank test. A multivariate analysis was performed using the Cox's proportional hazards model to determine the effect of pathological staging (lymph node involvement), ploidy and kinetic parameters. RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy. In univariate analysis, lymph node involvement, labelling index > 10% and Tpot < 5 days were associated with poor prognosis, with P= 0.0006, 0.049 and 0.029 respectively; no significant differences were found in Ts (P = 0.214), and ploidy (P= 0.095). In multivariate analysis, lymph node involvement, ploidy and Tpot were found to be independent factors of colorectal cancer prognosis (P= 0.028, 0.032 and 0.035 respectively) in all tumours. Tpot was considered a independent prognostic factor in diploid tumours (P= 0.047) but not in aneuploid tumours (P= 0.345). CONCLUSIONS: These results suggest that kinetic parameters determined by pre-operative biopsies of colorectal adenocarcinoma represent a prognosis factor, independent of pathological staging, particularly in diploid tumours.

Effect of radiation therapy on the potential doubling time of tumours in colorectal cancers.

OBJECTIVE: The aim of the present study was to investigate the effects of standard fractionated radiation therapy on the kinetic parameters of colorectal adenocarcinomas. METHODS: The study of tumour kinetics involved in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed with flow cytometry. This procedure provides a rapid calculation of qualitative parameters such as ploidy and quantitative parameters such as the in vivo S-phase fraction labelling index which indicates the percentage of cells that have entered into the cycle, the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy (group 1) and ten rectal carcinomas were studied following radiation therapy (group 2). In diploid tumours, the labelling index was significantly lower in the post-radiotherapy group than in the pre-radiotherapy group (2.7 +/- 1.1% versus 6.4 +/- 4.2%, respectively; P= 0.01), and the Tpot was significantly longer after radiotherapy (group 2) (22.0 +/- 7.0 days versus 8.6 +/- 6.0 days, P = 0.002). Standard fractionated radiation therapy also appears to result in a longer Tpot in diploid adenocarcinomas of the colon and rectum. This effect was not observed in aneuploid tumours. CONCLUSIONS: The effectiveness of hyperfractionated schedules of radiation therapy for aneuploid rectal tumours with short Tpot warrants further investigation in a larger patient population.

Cell proliferation in colorectal adenocarcinomas: comparison between Ki-67 immunostaining and bromodeoxyuridine uptake detected by immunohistochemistry and flow cytometry.

We compared three different means of assaying tumor proliferative activity in 30 human colorectal adenocarcinomas labeled in vivo with bromodeoxyuridine (BrdUrd). The labeling indices (LI) of BrdUrd obtained both by flow cytometry (FCM) and immunohistochemistry (IH) were also compared with the labeling index of Ki-67. These methods were then related to tumor ploidy and pathological features. Flow cytometry was performed in accordance with Begg's method after intravenous infusion of BrdUrd four hours before surgery. Immunohistology was carried out on paraffin-embedded sections with monoclonal antibodies against BrdUrd and Ki-67. A positive correlation was found between BrdUrd LI obtained by both FMC and IH (p<0.0001), a finding that complies with the literature. However, we report on a correlation between Ki-67 LI and BrdUrd LIs in colorectal tumors (p=0.012). The results were valid for all tumors when they were subdivided into diploid and aneuploid groups. The labeling indices were significantly higher in the aneuploid tumor group than in the diploid group (p=0.047). No relationship between proliferation parameters and tumor stage or grade was found. To our knowledge, this is the first report on a positive correlation between tumor proliferation indices in BrdUrd LIs and Ki-67 in colorectal carcinomas. This finding validates the value of Ki-67 immunostaining, which, however, should be confirmed in a larger series under the same technical conditions.

[Combination of 5-FU, high dose methotrexate, epirubicin and cisplatin (FEMTX-P protocol) in non surgical or locally recurrent metastatic gastric cancers]. / Association de 5-FU, méthotrexate à haute dose, épirubicine et cisplatine (FEMTX-P) dans les cancers gastriques métastatiques, inopérables ou en récidive locale.

In this phase II study, fifty patients with unresectable locally advanced and/or metastatic gastric carcinoma were treated with methotrexate 1.5 g/m2 iv and 5-fluorouracil 1.5 g/m2 iv on day 1; leucovorin rescue 15 mg/m2 orally every 6 h for 8 doses on day 2 and 3; epirubicin 60 mg/m2 iv and cisplatin 50 mg/m2 iv on day 15, q 4 weeks. The median age of the patients was 59 years and their median performance status 1. In forty-eight patients evaluable for response, five (10.4%) of the patients achieved a complete response and seventeen (35.6%) obtained a partial response (total response rate 46%; 95% confidence interval: 32%-60%). The median duration of response was 8+ months (range: 5-25 months). The median duration of survival of all patients was 10 months (range: 1-25+ months). Toxicities > grade 2 included vomiting grade 3 (31%), leucopenia grade 4 (18%) and thrombocytopenia grade 4 (4%). Treatment postponement or dose reduction for hematologic toxicity was necessary in 54% of patients. Median survival was 10 months. In conclusion, the FEMTX-P regimen is an active treatment in advanced gastric carcinoma with acceptable toxicity.

[Photodynamic therapy by coloring laser. Can it represent a therapeutic alternative for small epidermoid cancers of the esophagus?]. / La photothérapie dynamique par laser à colorant. Peut-elle représenter une alternative thérapeutique pour les petits cancers épidermoïdes de l'oesophage?

Our aim was to assess the efficacy of photodynamic therapy in inoperable patients with small esophageal carcinoma. Eleven patients were treated for squamous cell carcinomas ranging in size from 1 to 3 cm2. Hematoporphyrin (between 3 and 5 mg/kg) was injected intravenously and then the tumor irradiated at endoscopy 72 hours later with a dye laser (630 nm) at an energy of 250 joules/cm2. Complete destruction of the lesion was obtained in 6 cases with negative biopsies at 1 month. In all 6 patients, no recurrence was seen after a median follow-up of 4 months (range: 2-38). Partial destruction of the tumor was obtained in 4 cases while treatment was a complete failure in the last patient. Two instances of mild cutaneous photosensitization occurred. Two patients treated for recurrence after radiotherapy, died of esophageal perforation directly related to the procedure. Photodynamic therapy appears to be a possible effective treatment for esophageal squamous cell carcinoma in inoperable patients when other curative treatment modalities are not possible.