ABSTRACT
BACKGROUND: Chemotherapy is widely used in patients with recurrent head and neck cancer, but no clear markers are available that can predict response to treatment or survival in these patients. METHODS: Twenty-nine patients evaluated in this study had recurrent head and neck squamous carcinomas, previously treated with surgery and/or radiotherapy. Patients received either cisplatin and 5-fluorouracil (5-FU) (n = 15) or cisplatin and paclitaxel (Taxol) (n = 14). Expression of c-erbB2, p53, glutathione S-transferase pi, multidrug resistance-associated protein, thymidylate synthase, and glutathione synthetase were evaluated in biopsy tissues. RESULTS: Response to chemotherapy was significantly correlated with improved survival (progression-free survival, p =.0005; overall survival, p =. 007). Of the factors examined, expression of c-erbB2 was associated with significantly decreased progression-free survival (p =.023) and overall survival (p =.029). This was seen in patients treated with cisplatin/taxol but not in patients treated with cisplatin/5-FU. CONCLUSION: Expression of c-erbB2 may be a clinically useful predictor of survival in this group of patients.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/mortality , Receptor, ErbB-2/analysis , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Recurrence, Local , Paclitaxel/administration & dosage , Prognosis , Survival RateABSTRACT
Neoadjuvant cisplatin-based chemotherapy has been widely used in the last decade for organ preservation or unresectable disease in advanced stage head and neck cancer. We examined the expression of a series of tumor markers that have been associated with chemotherapy resistance in pretreatment biopsies from 68 patients who received cisplatin-based neoadjuvant chemotherapy at either of two institutions. Patients received either cisplatin/5-fluorouracil (n = 49) or cisplatin/paclitaxel (n = 19). Expression of p53, glutathione S-transferase pi (GSTpi), thymidylate synthase (TS), c-erbB2, and multidrug resistance-associated protein was examined by immunohistochemistry. Expression of glutathione synthetase mRNA was measured by in situ hybridization. The overall response rate for cisplatin-based neoadjuvant treatment was 79%. The expression of several of the tumor markers was associated with resistance to neoadjuvant treatment, but none reached statistical significance. Overall survival (OS) was strongly correlated with the absence of p53 expression. The OS at 3 years was 81% in the p53-negative group, whereas it was 30% in the p53-positive group for patients treated with neoadjuvant chemotherapy (P < 0.0001). Expression of GST pi and TS was also significantly correlated with decreased OS after neoadjuvant treatment. At 3 years, the OS rate was 82% in the low GSTpi score group, compared to 46% in the high GSTpi score group (P = 0.0018). In the TS-negative group, the 3-year OS rate was 71% compared with 40% in the TS-positive group (P = 0.0071). We conclude that p53, GSTpi, and TS may be clinically important predictors of survival in patients receiving neoadjuvant chemotherapy for head and neck cancer.
