Track topics on Twitter Track topics that are important to you
The purpose of this study is to determine the effectiveness and side effects of a new combination and schedule of chemotherapy drugs in the treatment of head and neck cancer. Patients with advanced or recurrent head and neck cancer, which is untreatable by surgery or radiation therapy are eligible for this study. Standard treatment for advanced or recurrent head and neck cancer involves the use of chemotherapy.
Approximately 28,900 patients will be diagnosed with squamous cell cancers of the oral cavity and pharynx in the year 2002. Of these, an estimated 7,400 patients will present with metastases or develop recurrent disease, which is not amenable to surgery or radiation therapy. Palliative chemotherapy is thus the only treatment option. Currently, combinations of cisplatin and 5-fluorouracil are used as first line treatment strategies, with median times to progression of 2.5 to 3 months and median survival rates of 5 to 7 months. The time to achieve maximum response with combination therapy is on average 4 months.
Taxanes, with their unique mechanism of microtubule stabilization, have demonstrated response rates similar to standard, first line combination regimens. Several phase II studies have evaluated the efficacy of single agent docetaxel in head and neck cancer patients. Cumulative response rates were approximately 30%, with higher response rates observed in patients receiving no prior chemotherapy. Docetaxel has also been used in combination with cisplatin and cisplatin and 5-fluorouracil. Although response rates with such combination regimens were superior to the use of single agent docetaxel, grade 3 and 4 toxicities were also more prevalent.
Capecitabine (Xeloda®), a fluoropyrimidine carbamate, is an oral prodrug, which is converted in tumor tissues to 5-fluorouracil through multienzymatic activation. Capecitabine (Xeloda®) has documented activity in breast and colorectal cancers and is widely administered. Because 5-fluorouracil has efficacy in the treatment of head and neck cancer, it is reasonable to consider that such tumors will respond to capecitabine. To date, there are no published trials using capecitabine (Xeloda®) in the treatment of metastatic head and neck cancer patients. However, clinical trials are ongoing in the U.S. and Europe with promising results.
In preclinical models, a synergistic interaction between capecitabine and docetaxel has been documented. One possible explanation for the synergy is that docetaxel up-regulates tumor levels of thymidine phosphorylase, the enzyme essential for the activation of capecitabine and 5'-dFUrd to 5-fluorouracil. Clinically, O'Shaughnessy, et al. recently reported improved survival with docetaxel/capecitabine combination therapy in patients with metastatic breast cancer, who previously failed anthracycline-containing chemotherapy. In this phase III study, patients were stratified according to previous exposure to paclitaxel and then randomized to capecitabine (Xeloda®) (1250 mg/m2 twice daily, days 1-14) plus docetaxel (75 mg/m2 day 1, repeated every 21 days) versus docetaxel alone. Grade 3 and 4 toxicities were more common in the docetaxel/capecitabine combination arm. Capecitabine (Xeloda®) and docetaxel were interrupted and the dosages reduced by 25% in patients who experienced a second occurrence of a given grade 2 toxicity, or any grade 3 toxicity, suggesting that the starting dosages were perhaps too high.
The role of chemotherapy in metastatic head and neck cancer is limited to palliation of the symptoms of disease. Platinum and 5-fluorouracil combinations remain standard first line treatment strategies. The taxanes have been shown to have similar efficacy to such first line regimens and are often used as salvage treatment for patients with metastatic disease. Given that docetaxel has documented clinical efficacy in head and neck cancer and that there are preclinical data to suggest synergy with docetaxel and capecitabine, it is reasonable to consider using these agents in combination to treat head and neck cancer patients. Moreover, capecitabine and docetaxel have distinct mechanisms of action and no overlap of key toxicities. A recent phase I/II study by Tonkin, et al. in metastatic breast cancer patients demonstrated activity and less toxicity when docetaxel 30 mg/m2/week (day 1 and 8 q21 days) was combined with capecitabine 1800 mg/m2/day (14 of 21 days). In another phase I study by Nadella, et al. weekly docetaxel (36 mg/m2 ) was combined with 14 days of capecitabine (up to 1500 mg/m2/day) over a course of 28 days. Antitumor responses were observed in patients with breast, colon, and bladder cancers. Hence, we propose this study whereby patients with previously treated, metastatic/recurrent head and neck cancer will receive treatment with docetaxel and capecitabine.
To reduce the potential for toxicity, we will use a modification of the Nadella regimen. Docetaxel will be administered weekly at a dosage of 30 mg/m2 for 3 out of every 4 weeks and capecitabine will be administered at a flat dosage of 2000 mg per day (1000 mg p.o. b.i.d.) for two weeks out of every 4 weeks. The justification for using a flat dosage of capecitabine versus a calculated dosage is based on pharmacokinetic data that show no change in clearance of capecitabine with changes in BSA. We plan to use a fixed dose of 2000 mg qd (1000 mg q am and 1000 mg q pm). Fixed dosing of capecitabine is convenient and feasible, as shown in a prior University of Michigan study in breast cancer patients. In another study Schott, et al. informally piloted the combination of weekly docetaxel 36 mg/m2 and 1500 mg twice daily (3000 mg/day) x 14 days capecitabine in metastatic breast cancer patients, and found it to be without unexpected or untoward side effects. Additionally, to take advantage of the time course of upregulation of TP in the preclinical models, the capecitabine dose will be given on days 5-18. In a flat dosing scheme, the Nadella regimen would have administered an average dose of 2125 mg qd for 14 days, assuming an average BSA of 1.7 m2. We plan to round this dosage downward to 2000 mg per day x 14 days; therefore, our regimen will use a slightly lower dosage of capecitabine. We feel that our proposed slightly lowered dose (closer to Nadella phase I dosing vs. Tonkin) of capecitabine is justified for the following reasons:
1. The Nadella study was performed in a group of patients with solid tumor malignancies that were refractory to conventional therapy or for whom no effective therapy existed. ECOG performance status (PS) was 1 or 2 in 5/17 (30%) patients, 10/17 patients had received 2 or more lines of previous chemotherapy, and 7/17 patients had received previous radiotherapy. Based on data from previous treatment of head and neck cancer patients at the University of Michigan, the patient population to be enrolled in this trial is expected to be 60% PS 0 and 40% PS 1, and some will have received prior chemotherapy and/or radiotherapy. Like the Nadella patient population, a majority of our patients have been pretreated and are of poorer health.
2. Dose interruptions and modifications are built into the protocol so that appropriate changes in treatment can be made in patients with Grade I or II toxicity, before the toxicity becomes Grade III or greater. Since the docetaxel is given weekly, and the capecitabine is administered daily, if patients are experiencing toxicity within a cycle, the dose of either can be held or modified.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Head and Neck Cancer
University of Michigan Comprehensive Cancer Center
Active, not recruiting
University of Michigan Cancer Center
Published on BioPortfolio: 2014-07-23T21:50:32-0400
This phase II trial studies the side effects and how well docetaxel and capecitabine work in treating patients with squamous cell (thin, flat cells) carcinoma of the head and neck that has...
Recent progress in treatment of recurrent/metastatic SCCHN has been made with the introduction of the taxanes. Docetaxel as a single agent has a response rate of 22-42% and 17% in patients...
This purpose of this study is to compare the effects (good and bad) of chemotherapy (docetaxel) plus ZD1839 (Iressa, gefitinib) with docetaxel and placebo on the head and neck cancer to se...
This is a study for patients who have head and neck cancer that has recurred in the body area where they previously received radiation, and for whom surgery is not planned. A widely accept...
The goal of this clinical research study is to find the highest safe dose of the drugs OSI-774 and docetaxel that can be given together along with radiation treatment for advanced head and...
Tobacco and alcohol consumption are risk factors for developing head and neck cancer, and continuation postdiagnosis can adversely affect prognosis. We explored changes to these behaviors after a head...
Treatment sequelae such as trismus, shoulder dysfunction syndrome resulting from spinal accessory nerve palsy, and radiotherapy-induced neck fibrosis are often overlooked when in the management of hea...
Postoperative chemoradiotherapy (CRT) is considered standard of care in patients with locally advanced head and neck cancer with positive margins and/or extracapsular extension (ECE).
Perineural invasion (PNI) is a mechanism of tumor dissemination that can provide a challenge to tumor eradication and that is correlated with poor survival. Squamous cell carcinoma, the most common ty...
Information on re-irradiation (re-RT) for recurrent and second primary head and neck cancer is limited. Herein, a description of our long-term experience of re-RT for previously irradiated head and ne...
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)
A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.
Dissection in the neck to remove all disease tissues including cervical LYMPH NODES and to leave an adequate margin of normal tissue. This type of surgery is usually used in tumors or cervical metastases in the head and neck. The prototype of neck dissection is the radical neck dissection described by Crile in 1906.
A form of RHABDOMYOSARCOMA arising primarily in the head and neck, especially the orbit, of children below the age of 10. The cells are smaller than those of other rhabdomyosarcomas and are of two basic cell types: spindle cells and round cells. This cancer is highly sensitive to chemotherapy and has a high cure rate with multi-modality therapy. (From Holland et al., Cancer Medicine, 3d ed, p2188)
A symptom, not a disease, of a twisted neck. In most instances, the head is tipped toward one side and the chin rotated toward the other. The involuntary muscle contractions in the neck region of patients with torticollis can be due to congenital defects, trauma, inflammation, tumors, and neurological or other factors.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...