Head/neck cancer clinical studies

A clinical trial to evaluate misoprostol as a protector of normal tissue during a course of XRT in cancer patients suggests a reduction in acute normal tissue injury (215). A randomized, prospective, double-blind study indicates that topical misoprostol, administered as an oral rinse 15-20 min before irradiation using conventional 2-Gy (200 rad) fractions, five days a week over 6—7 weeks, significantly protects the oral mucosa from radiomucositis, a frequently observed normal tissue complication during XRT for head and neck cancer (215). 

Currently, 13-cis-retinoic acid is the most studied chemopreventive agent that decreases the incidence of second primary tumors in patients with head-and-neck cancer, reverses premalignant lesions, and reduces appearance of nonmelanoma skin cancer in patients with xeroderma pigmentosum. Unfortunately, this vitamin A derivative has a significant clinical toxicity, which limits its utility in a practice setting. 

Early clinical studies clearly demonstrated that cisplatin could be administered safely and concurrently with radiation therapy (73-75). Early clinical trials that demonstrated the promise of the combination of cisplatin and radiation therapy included the treatment of brain tumors (76,77), head and neck tumors (78), malignant melanoma (79), and bladder cancer (80). Early clinical trial integrating carboplatin administration with radiation therapy was carried out in patients with locally advanced nonsmall cell lung cancer (NSCLC) (81). A hypothesis put forth by Coughlin and colleagues (81) was that the best clinical outcomes would be achieved with the combination of cisplatin and radiation therapy in tumors that were responsive to cisplatin. 

The initial combination modality clinical studies with cisplatin and fractionated radiation therapy was carried out in head and neck cancer with weekly cisplatin (120-160 mg/m2) and conventional single daily fraction radiation (95). In a follow-up intergroup study, patients were randomized to radiation therapy alone or to radiation therapy plus 20 mg/ m2/wk cisplatin (96). Both studies showed no major increase in normal tissue toxicity in the radiation field and showed an increase in response rate. There was no increase in complete response rate or in survival. Bachaud et al.(97) carried out a randomized study comparing radiation therapy alone with concurrent cisplatin (50 mg/m2) and radiation therapy in postoperative patients. This trial produced a significant reduction in local recurrence and improved disease-free survival with 59% of the patients receiving the full planned dose of cisplatin. 

The common link with many clinical studies of chemoradiation in head and neck cancers is the significant mucositis that patients experience during therapy. Acrein has reported on a trial that attempts to deliver Ethyol as a protective agent to lessen the side effects of weekly paclitaxel (134). 

Although most of the studies using nonviral vectors are being performed in animal models, O Malley and colleagues have performed IL-2 gene therapy by using nonviral vector in patients with advanced head and neck cancer. In their phase I clinical trial, cationic liposomes prepared with CMV-IL-2 plasmid were injected into the tumor. All patients completed the study but most died due to the progression of the disease. One patient exhibited a decrease in the burden of the tumor. 

The first clinical trial of electrochemotherapy was published in 1993 [29], with treatment of cutaneous metastases from head and neck cancer. This was followed by several studies of pahents with malignant melanoma metastases and basal cell carcinoma [30, 31]. In the first study, intravenous or intraarterial bleomycin was used, and in the latter intratumoral injechon of 5 U ml" was used, for both the tumor and the surrounding area. In the first study, plate electrodes were used, where as in the latter a needle electrode device was used. 

Putti, T.C., To, K.E., Hsu, H.C. et al. (2002) Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression a multicentre immunohistochemical study... 

PET could improve the delineation of GTV in some tumor entities like brain tumors, lung cancer, and head and neck cancer. Therefore, its impact on the clinical outcome has to be evaluated in prospective trials. The role of PET for the visualization of tumor biology is unclear. However, this approach could open new perspectives in treatment planning and monitoring of solid tumors and has to be assessed in the future in experimental and clinical studies. 

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