Concomitant chemoradiotherapy followed, where feasible, by surgery for cancer of the esophagus.

PURPOSE: To conduct a multicenter phase II study of a concomitant combination of chemotherapy and radiotherapy followed by surgery, where feasible, in patients with nonmetastatic esophageal tumor, stratified on operability at diagnosis. METHODS: Each cycle consisted of fluorouracil (5FU) 800 mg/m2/d by continuous intravenous (IV) infusion on days 1 to 5, cisplatin (CDDP) 50 mg/m2/d IV bolus on days 1 and 8, hydroxyurea (HU) 1.5 or 2 g/d orally on days 8 to 12 and concomitant radiotherapy 20 Gy in 10 fractions over 12 days. All patients were to receive two cycles on days 1 and 22. If feasible, surgery was performed 3 to 6 weeks after cycle two completion. Otherwise, a third cycle was administered. RESULTS: Eighty-eight patients were included between September 1990 and September 1993. Of the 47 operable patients, 41 (87%) underwent surgery and 38 (81%) had a complete resection. No residual primary tumor was found in the surgical specimen in 17 cases (36%), and only microscopic foci in 13 (28%). Two-year overall and disease-free survival probabilities were 51% (95% confidence interval [CI]; 37 to 65) and 43% (95% CI, 28 to 57), respectively. Among the 41 inoperable patients, 12 (29%) became operable. Seven (17%) had complete resection, two incomplete resection, and three exploratory surgery. Two-year overall and disease-free survival probabilities were 29% (95% CI, 15 to 43) and 27% (95% CI, 13 to 40), respectively. Five deaths occurred during chemoradiotherapy, six postoperatively and four in patients with evidence of cancer. Five late complications (one myelopathy) were observed. CONCLUSION: Despite a high histologic response rate in initially operable patients, overall survival was similar to that observed in other preoperative chemoradiation series because of substantial toxicity.

Synchronous and metachronous head and neck carcinomas.

BACKGROUND: The incidence of head and neck cancer is increasing. To improve the survival of head and neck cancer patients, an effective program of screening and/or chemoprevention of second malignancies is essential. An analysis of the incidence, time to development, and risk factors of second malignant tumors in head and neck cancer patients can contribute to the design of effective screening and chemoprevention programs. METHODS: Eight hundred, fifty-one patients with initial squamous cell carcinoma of the larynx (n = 224), tonsils (n = 189), pyriform sinus (n = 165), oral cavity (n = 129), mobile tongue (n = 72), and base of tongue (n = 72) treated from 1978 to 1990 were analyzed for the presence of a second malignancy after initial therapy. Of these 851 patients, 544 (64%) were documented smokers and 35 (4%) were nonsmokers. No smoking information was available for 272 patients. Four hundred, fifty-four patients (53%) were consumers of alcohol and 64 patients (8%) were nondrinkers. Alcohol consumption information was not available for 333 patients. RESULTS: One hundred, sixty-two (19%) second head and neck carcinomas occurred in the original 851 patients. Sixty-six patients (41%) had synchronous tumors, and 96 patients (59%) had metachronous tumors. The probability of developing a second metachronous cancer 5-years after undergoing treatment for the initial head and neck cancer was 22%. Borderline statistical significance was observed in the 5-year second cancer incidence based on the site of the initial primary cancer (46% for the base of tongue, 34% for the pyriform sinus, 23% for the larynx, 18% for the oral cavity, 15% for the tonsils, and 10% for the mobile tongue). Tobacco smoking (3% for nonsmokers vs. 26% for < or = 20 pack-years vs. 42% for > 20 and < or = 40 packs/year vs. 30% for > 40 packs/year of smoking) and the consumption of alcohol (5% for non-drinkers vs. 32% for drinkers) were both statistically significant in predicting the likelihood of developing a second malignancy. Multivariate analysis revealed that the two independent variables that influenced the occurrence of a second metachronous cancer were the anatomic site of the original primary cancer and patient age. The survival rate after the second cancer was influenced significantly by the site of the second cancer (20% for a second head or neck cancer, 3% for a second esophageal cancer, and 2% for a second lung cancer). Continued smoking (20% for non-smokers vs. 5% for smokers) and continued alcohol consumption (27% for nondrinkers vs. 6% for drinkers) also adversely influenced the survival after the occurrence of a second cancer. CONCLUSIONS: This study confirms the high rate of second cancers in patients with initial head and neck malignancies. The development of a second malignancy is almost always fatal. Screening programs and chemoprevention trials should be directed toward cancer patients with initial head and neck cancers. Only the small subset of nonsmokers and nondrinkers should be excluded from such trials.

[Cancer of the breast: intensive treatment with bone marrow autografts]. / Cancer du sein: traitement intensif avec autogreffe de moelle.

High dose chemotherapy with autologous bone marrow transplantation has been proposed in metastatic and inflammatory breast cancer. Data in the literature reported an improvement of the quality and of the rate of response. However, the impact on survival remains to be demonstrated. Since 1985, a pilot study in inflammatory and directly metastatic breast cancer has been started in order to determine the impact of high dose chemo-radiotherapy. Patients were treated with an induction regimen consisting of cyclophosphamide 1,200 mg/m2 and 4'epi-adriamycin 75 mg/m2 every 15 days x 4. Mastectomy was performed associated for patients younger than 50 years with bone marrow collection and cryoconservation. In this group, late intensification with cyclophosphamide 2.2 g/m2 day 1 and 2, TBI and autologous bone marrow transplantation was performed. Fourteen patients have been treated: 9 inflammatory breast cancers T4 b N1 M0, 5 metastatic cancers at presentation including 3 with inflammatory breast cancer T4 b N1 M1 and 2 metastatic T2 N1 M1. Relapses had occurred in 7 patients, of them 4 were metastatic. Five patients died from their disease, and one from CMV interstitial pneumonitis. Six patients are alive free of disease but only one was metastatic. On this limited number of patients, survival of metastatic breast cancers does not seem to benefit from this regimen.