mesna and Head-and-Neck-Neoplasms

Squamous cell carcinoma of the head and neck (SCCHN) is a functionally and cosmetically devastating tumor, and its treatment and the economic costs associated with aggressive treatment are substantial. Even with aggressive standard local surgery, radiotherapy, or both, locally advanced tumors recur in approximately two thirds of patients and the prognosis for those whose disease recurs or metastasizes is dismal. Newer chemotherapeutic agents such as ifosfamide and taxanes (paclitaxel [Taxol; Bristol-Myers Squibb Company, Princeton, NJ] and docetaxel) have shown higher response rates than those seen with conventional agents and renew hope of prolonged survival, improved quality of life, and greater convenience. We recently conducted two consecutive phase II studies using paclitaxel/ifosfamide/cisplatin and paclitaxel/ifosfamide/carboplatin for patients with recurrent or metastatic SCCHN. These two regimens yielded high response rates (including complete responses) and appear to be promising therapies for SCCHN. This report describes our experience with these two regimens, including a comparison of their toxic effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials as Topic; Head and Neck Neoplasms; Humans; Ifosfamide; Mesna; Neoplasm Recurrence, Local; Paclitaxel; Taxoids

Malignant triton tumor (MTT) is a relatively rare, aggressive tumor comprised of both malignant schwannoma cells and malignant rhabdomyoblasts. Because MTT frequently arises in the head and neck, the otolaryngologist must be aware of the nature of the tumor and its response to various treatment modalities.. This article reviews the treatment and outcome of all reported cases of MTT arising in the head and neck.. Although statistical analysis is limited by the short duration of follow-up of many patients, complete tumor resection appears to carry an improved chance of survival. Adjuvant radiation and chemotherapy may also improve survival, although a benefit of these therapies was not well demonstrated in this small series.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Etoposide; Fatal Outcome; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Lung Neoplasms; Magnetic Resonance Imaging; Mesna; Neoplasm Recurrence, Local; Neurilemmoma; Radiotherapy Dosage; Vincristine

This Phase II trial was conducted to determine the response rate, particularly of the primary sites, tolerability, and toxicity of induction chemotherapy of paclitaxel, ifosfamide, and carboplatin for patients with previously untreated locally advanced squamous cell carcinoma of the head and neck (SCCHN). We also hypothesized that improved complete response (CR) rates with the induction chemotherapy may render better survival rates with subsequently delivered definitive local treatment.. All eligible patients with locally advanced SCCHN received two courses of induction chemotherapy and underwent repeated head and neck examination and computed tomography or magnetic resonance imaging scans. If the patients achieved responses (CR or partial [PR]), they received two more courses of chemotherapy before undergoing definitive local treatment. Induction chemotherapy consisted of paclitaxel (T; 175 mg/m(2) in a 3-hour infusion) on Day 1, ifosfamide (I; 1000 mg/m(2) in a 2-hour infusion) on Days 1-3 with intravenous mesna (200 mg/m(2) before and 400 mg/m(2) after ifosfamide), and carboplatin (C) using the Calvert formula for the area under the plasma concentration-versus-time curve of 6 on Day 1, repeated every 3-4 weeks. Prophylactic hematopoietic growth factors or antibiotics were not used in this study. Definitive local treatment was given based on the investigators' preference.. Fifty-four patients were registered and 52 patients were assessable for response to induction chemotherapy; 2 were not evaluable. After four courses of induction chemotherapy, the CR rates of the primary and lymph node sites were 60%, and 41%, respectively. For both primary and lymph node sites, there were 31% CRs and 50% PRs with an overall response rate of 81%. Five (9%) patients developed neutropenic fever, all of whom recovered with antibiotic therapy. Two (4%) patients had infection without neutropenia and recovered without any complication. Grade 3/4 thrombocytopenia and anemia occurred in three (6%) and four (7%) patients, respectively. Grade 3/4 fatigue developed in four (7%), arthralgia/myalgia in two (4%), peripheral neuropathy in two (4%), and orthostatic hypotension in two (4%) patients. One patient died of severe anaphylaxis although a maximized resuscitation effort was made. With a median follow-up of 22 months, the organ preservation rate was about 81% (42 of 52 patients). Although survival rates were not primary end points in this study, with a median follow-up of 22 months, 43 (83%) patients are still alive. Overall 1 and 2-year survival rates were 88% and 82%, respectively. Disease-free 1 and 2-year survival rates were 88% and 77% respectively.. TIC induction chemotherapy is associated with a high CR rate at the primary sites and with excellent survival and organ preservations rates with subsequently delivered definitive local therapy. The regimen was also well tolerated in the majority of patients. The TIC regimen should be developed further in the context of induction chemotherapy followed by concomitant chemoradiotherapy or with specific molecular targeted agents.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Male; Mesna; Middle Aged; Paclitaxel; Survival Rate; Taxoids

Chemotherapy has not significantly altered the overall survival of patients with recurrent squamous cell carcinoma of the head and neck; therefore, the development of new agents is essential. The purpose of the current phase II study was to define the efficacy of ifosfamide in the treatment of recurrent squamous cell carcinoma of the head and neck. All patients were required to have squamous cell carcinoma of the head and neck that had recurred following surgery or radiotherapy or both. Patients may have received prior chemotherapy. Patients were initially treated with ifosfamide 2 g/m2/day for 4 days (dose level 0). Dose level-1 was 2 g/m2/day for 3 days, and dose level-2 was 2 g/m2/day for 2 days. All patients received mesna 400 mg/m2/day prior to and 1,200 mg/m2/day as a continuous infusion after ifosfamide. Thirty-eight patients were enrolled in the study. Five patients were inevaluable for toxicity or response. Overall, the regimen was well tolerated, with grade 4 granulocytopenia the only significant toxicity occurring in 16 patients. Overall, eight of 31 evaluable patients (25.8%) had a major response. Only one of the 10 patients (10%) with prior chemotherapy responded, but seven of the 21 patients (33.3%) with no prior chemotherapy had major responses. Ifosfamide is an active agent in recurrent squamous cell carcinoma of the head and neck. Further studies of ifosfamide in combination with other agents, particularly as induction therapy in patients with locally advanced disease, are warranted.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Agents, Alkylating; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Infusions, Intravenous; Injections, Intravenous; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Survival Rate

A total of 37 men with epidermoid head and neck cancer whose disease had recurred following primary treatment (surgery and/or radiotherapy) received first-line chemotherapy with ifosfamide at i.v. doses of 3 g/m2 given daily on 3 consecutive days in combination with mesna (600 mg/m2 x 3 oral daily doses on days 1-3) every 3 weeks. In all, 7 patients showed a partial response and 2 patients achieved a complete response, for an overall objective response rate of 26% (9 of 35 eligible patients; 95% confidence interval, 12.5%-43%). Excluding the 5 early nontoxic deaths observed during the first 3 weeks of therapy, the objective response rate was 30% (9 of 30 patients; 95% confidence interval, 15%-49.5%). Responses were seen in lung metastases (2 patients), lymph nodes (2 patients), skin (3 patients), and cases of local recurrence (5 patients). The median duration of responses was 3 months (range, 2-5 months). The main side effects of ifosfamide were alopecia (83% of patients), emesis (80%), granulocytopenia (23%), and mild mucositis (20%). Two poor-risk patients suffered severe CNS complications that were probably related to treatment. Three patients died due to chemotherapy-related complications (2 patients with CNS toxicity and 1 patient with granulocytopenic sepsis). In conclusion, ifosfamide appears to be an active drug in epidermoid head and neck cancer and merits further evaluation in this disease.

Topics: Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Ifosfamide; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local

High-dose ifosfamide/mesna was administrated to 28 mostly pretreated patients with locally advanced and metastatic head and neck cancer who failed conventional surgery/radiation treatment. Primary sites include tongue (5), salivary gland (3), floor of mouth (5), oropharynx (2), hypopharynx (5) and larynx (8). The dose and schedule of ifosfamide (IF) was 3.5 g/m2 8 h, i.v. infusion, days 1-5, every 28 days, and mesna was given as 20% of IF dose intravenous bolus injection at 0, 2, 4, 6 and 8 h; mesna 40% of IF dose was given by oral route at 10 and 12 h, days 1-5, every 28 days. All patients were evaluable for both toxicity and response. 14 patients had received prior treatment with surgery plus radiation therapy and 14 patients radiation therapy. Following chemotherapy, 4 patients (14.2%) achieved complete remission and 8 patients (28.5%) achieved partial remission, with an overall response rate of 42.7%. Toxicity was reported for 186 cycles and ranged from mild to moderate: anemia 4, leukopenia 6, thrombopenia 1, nausea and vomiting 12, alopecia 28, microscopic hematuria 3, increased transaminase 1. No CNS symptoms and renal toxicity were registered. Median duration of survival is 11+ months (range 3+ to 18+ months). Nine patients died. We conclude that ifosfamide/mesna at this dose and schedule has a significant activity in recurrent head and neck cancer, and produces minimal toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Male; Mesna; Middle Aged

Thirty-six patients with recurrent carcinoma of the head and neck and no prior exposure to chemotherapy were treated with Ifosfamide. This drug was administered, concomitantly with Mesna, as a 24-hr infusion at a dose of 5-6.25 g/m2 every 3 weeks. Objective activity in 32 evaluable patients was 28% (9/32, 95% C.I. 17%-39%); 40% of patients had leukocyte values less than 2000 mm3 and 6% platelets less than 50,000 mm3. Nonhematologic toxicity consisted mainly of nausea/vomiting (66% greater than or equal to grade 2) and alopecia (80% greater than or equal to grade 2). The activity encountered warrants further studies with this drug in head and neck cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Drug Evaluation; Head and Neck Neoplasms; Humans; Ifosfamide; Leukocyte Count; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local; Platelet Count; Survival Rate

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Clinical Trials, Phase II as Topic; Data Interpretation, Statistical; Endpoint Determination; Head and Neck Neoplasms; Humans; Ifosfamide; Mesna; Neutropenia; Paclitaxel; Reproducibility of Results; Survival; Taxoids