Pilot study of intraoperative chemotherapy with cisplatin and 5-fluorouracil in patients with advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Intraoperative manipulation of the tumor during cancer surgery has long been recognized as a source of metastasis and contamination of the surgical wound during tumor removal. We explored the use of intraoperative chemotherapy to minimize the risk of tumor cell implantation and metastasis during head and neck cancer surgery and conducted a dose escalating intraoperative chemotherapy clinical trial designed to assess the feasibility of this approach and associated toxicities in patients with advanced squamous cell carcinoma of the head and neck. METHODS: Fourteen patients were treated with 5-fluorouracil at a dose of 1000 mg/m(2) administered intravenously over an 8-hour period during the surgery with simultaneous cisplatin. The cisplatin dose was escalated and toxicity observed. Cisplatin at 75 mg/m(2) was chosen as the maximum tolerated dose level. RESULTS: One patient experienced a grade 3 nephrotoxicity, 1 patient a grade 1 neuropathy, and 5 patients grade 2 nausea (36%). There were no grade 4 toxicities. CONCLUSION: Intraoperative chemotherapy is feasible, and the combination of cisplatin at 75 mg/m(2) and 5-fluorouracil at 1000 mg/m(2) can be administered during surgery without significant toxicity.

Prognostic significance of G1 cell-cycle inhibitors in early laryngeal cancer.

BACKGROUND: Radiation therapy yields a 2-year local control rate of 80% to 90% in early laryngeal squamous cell carcinoma. However, a subset of early laryngeal cancers has a significantly higher rate of local recurrence and lower rate of overall survival. OBJECTIVE: The objective of this study was determine the prognostic significance of p53, p27, and p21 expression in patients with early laryngeal cancer. METHODS: Expression of p53, p27, and p21 proteins in pretreatment biopsies from sixty-eight patients was analyzed by using immunohistochemistry. Low (10% cells) levels of expression were measured. All patients were newly diagnosed and treated with external beam radiation. Other contributing factors were also studied, such as age, sex, race, tumor site, and stage. RESULTS: Forty (58.8%) and 28 (41.2%) lesions were staged as T1 and T2, respectively, whereas 16 (23.5%) and 52 (76.5%) were located in the supraglottis and glottis, respectively. Overexpression of p27, p53, and p21 was found in 36.7%, 60.6%, and 60% of cases, respectively. Overexpression of p27 was found to be a significant predictor of recurrence by multivariate analysis (RR 3.3, P = .017). Overexpression of p21 and/or p53 was not predictive of recurrence. No factor predicted disease specific or nonspecific overall survival. CONCLUSION: Our results indicate the significance of p27 overexpression as an indicator of recurrence in patients with early laryngeal squamous cell carcinoma.

Correlation of histopathological variants, cellular DNA content, and clinical outcome in adenoid cystic carcinoma of the salivary glands.

OBJECTIVE: To study the correlation between flow cytometrically measured DNA ploidy with prognostically important histopathologic groups and clinical outcome in patients with adenoid cystic carcinoma of the salivary glands. STUDY DESIGN: 46 tumor specimens were analyzed flow cytometrically for DNA content and assessed for histological grade. Correlations were made between tumor DNA ploidy and histopathological grade, and disease-free and overall survival of these patients. RESULTS: Of the 46 patients, 31 had a cribiform/tubular histologic pattern, and 15 had a solid pattern. 84% of the tumors with cribriform/tubular pattern were DNA diploid, compared with 33% of tumors that were graded solid. This difference proved to be statistically significant (chi(2)11.75, P = 0.0006). Overall and disease-free survival periods were longer for patients with DNA diploid tumors in both groups, 63% vs. 36% and 62% vs 38%, respectively. CONCLUSIONS: Tumor DNA ploidy correlates with prognostically important tumor histopathology as well as overall and disease-free survival in patients with adenoid cystic carcinoma of the salivary gland. EBM RATING: B-3.

Prognostic significance of p53 and FHIT in advanced oropharyngeal carcinoma.

OBJECTIVE: To determine the prognostic significance of p53 and fragile histidine triad (FHIT) expression in advanced oropharyngeal squamous cell carcinoma. STUDY DESIGN: A retrospective collection of clinical data was correlated with the protein expression. METHOD: The expression of p53 and FHIT in specimens from patients with previously untreated advanced squamous cell carcinoma of the oropharynx was determined by immunohistochemistry. The expression of p53 and FHIT was statistically correlated with survival outcome. The primary endpoints were overall survival and disease-free survival. RESULTS: Thirty-four patients were analyzed in this study. Overexpression of p53 was observed in 41.2% (14/34) of tumors and was associated with a trend toward an improved overall survival using univariate (P =.1088, risk ratio [RR] = 0.503) and multivariate (P =.1533, RR = 0.470) analyses. Marked reduction or complete absence of FHIT expression was observed in 57.6% (19/33) of tumors. Patients with tumors showing no reduction in FHIT expression had a lower overall survival using univariate (P =.04, RR = 2.27) and multivariate (P =.013, RR = 4.41) analyses. CONCLUSION: Overexpression of p53 predicted a trend toward an improved prognosis, whereas no reduction in FHIT expression predicted a significantly poorer outcome in patients with advanced oropharyngeal cancer.