Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors discuss the results of 3 studies of their group reflecting the possible role of amifostine in simultaneous radiochemotherapy (RCT) of advanced head and neck cancer. In a controlled phase II trial (1995 through 1996), 39 patients were included in this pilot investigation. A control group (n = 14) received simultaneous RCT of the head and neck region with an irradiation dose of 60 Gy and 2 cycles of carboplatin (700 mg/m(2) cumulative dose). Twenty-five patients received the same basic therapy and an additional 500-mg dose of amifostine before each chemotherapy. Amifostine was administered less than 45 minutes before the end of radiotherapy. The authors observed a dramatic reduction of typical radiotherapy-associated toxicities (mucositis, xerostomia, loss of taste, dysphagia). The hematologic side effects (leukocytopenia, anemia, thrombocytopenia) also were decreased significantly. The overall survival rate and locoregional control of both groups were comparable after 12 months. In a controlled intensification trial (1997 through 1999), the authors included 76 consecutive patients (69 men, 7 women) with pharyngeal cancer (oropharynx, n = 33; hypopharynx, n = 43). The tumors were characterized as unresectable and locally advanced without distant metastasis. All patients received a conventional radiotherapy (2-Gy single dose, daily fractionation) up to doses of 60 Gy and an additional 10 Gy as a boost in the tumor-infiltrated region. A dose of carboplatin, 70 mg/m(2), was given to a group of 45 patients on days 1 through 5 and 29 through 33 of radiotherapy (RCT arm). The resulting cumulative dose was 700 mg/m(2). A group of 31 patients (RCTintens arm) received the same dose of carboplatin on days 1 through 5, 22 through 26, and 43 through 47 or 1 through 5, 15 through 19, 29 through 33, and 43 through 47 of radiotherapy (cumulative dose 1.05 to 1.40 mg/m(2)). All patients received 500 mg of amifostine before each carboplatin administration. If the tumor volume was less than 20 cm(3), we observed an increased 1-year overall survival rate (91% v 71%) and time to progression (17 months v 10 months). If the tumor volume was greater than 20 cm(3), we observed comparable treatment results in both groups (1-year survival rate, 60% v 61%; time to progression, 13 months v 12 months). In a long-term follow-up investigation (1999 through 2000), 531 patients (89 women, 442 men) were analyzed according to their toxicities during regular follow-up investigations at our outpatient facility. All patients were treated by surgery or radio(chemo)therapy because of an advanced head and neck cancer. A total of 218 of 531 patients received the antineoplastic therapy without cytoprotection. An additional 313 patients received their RCT combined with amifostine administration before administration of the radiosensitizer. A significant influence of cytoprotection was registered in the following toxicities: xerostomia, fibrosis, loss of taste, and dysphagia. No impact was seen on the development of interstitial lymph edema and esophageal stenosis. Amifostine could be integrated in simultaneous radiochemotherapy of advanced head and neck cancer patients. The authors favor the administration of amifostine before chemotherapeutics alone. Selective cytoprotection could decrease the main acute toxicities (mucositis, xerostomia, dysphagia) as well as late side effects (xerostomia, loss of taste, fibrosis) of this form of combined treatment. The enhanced therapeutic index may be changed into a prognostic benefit for selected patients with unresectable tumors, if the volume is smaller than 20 cm(3).
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PMID:Amifostine in simultaneous radiochemotherapy of advanced head and neck cancer. 1191 77

The treatment of head and neck cancer continues to evolve. The recent use of aggressive chemoradiotherapy protocols has resulted in significant morbidity involving mucositis, dysphagia, and a higher rate of feeding tube dependency. We have initiated a randomized phase II study with concomitant chemoradiotherapy with or without subcutaneous amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD). This article presents a detailed background, rationale, and endpoints for this study and discusses future directions in the treatment of head and neck cancer.
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PMID:Phase II randomized study of concomitant chemoradiation using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with newly diagnosed locally advanced squamous cell carcinoma of the head and neck. 1472 46

Concurrent chemotherapy and radiation has improved the outcome for patients presenting with locally advanced squamous cell carcinomas of the head and neck (SCCHN). These improvements have come at a cost of increased treatment-related toxicities. We previously reported the results of a phase II trial examining the role of concurrent carboplatin, paclitaxel, and daily radiotherapy (RT) in SCCHN. In an attempt to decrease these side effects, we conducted a prospective phase II trial evaluating the role of amifostine (Ethyol, MedImmune Oncology, Inc, Gaithersburg, MD) in patients treated with this concurrent chemoRT scheme. From April 2002 to September 2004, 19 patients with stage III-IV SCCHN were enrolled on a prospective phase II trial. Treatment consisted of daily RT delivered to 70.2 Gy (1.8 Gy/fx) with amifostine 500 mg IV (<1 hour before RT), and concurrent weekly carboplatin (100 mg/m2) and paclitaxel (40 mg/m2). Median age was 58.5 years (range, 48 to 70 years); male to female ratio was, 83%:17%; Caucasian versus other was, 61%/39%. Tumor characteristics based on histology were: primary cancers of the oropharynx (55.6%); supraglottic larynx (16.7%); hypopharynx (16.7%); oral cavity (5.6%); and unknown primaries (5.6%). All patients presented with locally advanced, unresectable disease T4 (50%), T3 (27.8%), and advanced nodal disease (N2b-N3) (78%). Toxicities were measured weekly during treatment and at each follow-up visit. Disease response to therapy was determined 2 months after completion of therapy. Seventeen patients are evaluable for response and survival at 2 months following completion of RT. Eighty-four percent completed the prescribed radiation treatment, and 84% of patients received more than six cycles of chemotherapy. The median number of missed chemotherapy cycles was 1.5 (range, 0 to 5 cycles). Fifty-six percent of patients received more than 90% of prescribed amifostine doses, with chemoRT-related toxicity being the most common reason for withholding the dose (77%). Median doses of missed amifostine were three (range, 0 to 30 doses). Grade 3 toxicities associated with therapy were: mucositis and dysphagia (40% of patients each), dehydration (27%), xerostomia (20%), and dermatitis (20%); 53% of patients experienced grade 3 leukopenia, while grade 3/4 neutropenia developed in 20%/13%. No grade 4/5 nonhematologic toxicities were encountered. Forty percent of patients completed RT without unscheduled treatment breaks secondary to treatment-related toxicity. Median treatment-break time was 5 days (range, 0 to 20 days). Clinical complete response at both the primary site of disease and neck was achieved in 75% of patients 2 months following completion of RT. Weekly carboplatin and paclitaxel administered concurrently with definitive RT and daily amifostine is well tolerated, with over 85% of patients completing therapy with acceptable toxicity. The addition of amifostine appears to decrease treatment-related toxicity without impacting efficacy.
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PMID:The evaluation of amifostine for mucosal protection in patients with advanced loco-regional squamous cell carcinomas of the head and neck (SCCHN) treated with concurrent weekly carboplatin, paclitaxel, and daily radiotherapy (RT). 1572 15

Current therapeutic approaches for lung cancer favor treatment intensification, with the presumption that dose-intense chemotherapy regimens and/or higher radiation therapy (RT) doses or novel fractionation schemes will result in increased patient survival. Also, the trend for non-operative therapy has favored concurrent over sequential regimens. The incidence of severe acute esophagitis in patients treated for lung cancer with standard (once daily) RT alone is 1.3%, and induction chemotherapy increases the risk of severe acute esophagitis slightly over that of standard RT alone. In contrast, a strong radiosensitizing effect of chemotherapy given concurrently with standard thoracic RT (chemoRT) is associated with an incidence of severe esophagitis of 14% to 49%. Acute esophagitis may be severe and disabling, and result in hospitalization, placement of a feeding tube in the stomach or intravenous feedings, and steady supportive care. Also, RT may need to be halted temporarily to allow for healing of the esophageal lining; treatment breaks in turn decrease survival of patients with unresectable lung cancer. Therefore, esophagitis as a dose-limiting toxicity of chemoRT may have a direct impact on tumor control and survival. Aggressive types of RT fractionation have also been associated with worsening esophagitis grades and duration. Moreover, it is commonly assumed in the radiation oncology clinic that the longer the length of the esophagus segment included in the RT field the higher the probability of esophageal toxicity, although differing opinions are commonly expressed. Recent advances in 3-dimensional conformal RT allow a unique chance to gain volumetric data pertaining to organ damage rather than rely on older estimates based on organ length (eg, esophagus) or portion (ie, lung, spinal cord). The Radiation Therapy Oncology Group (RTOG) conducted a large phase III, randomized study RTOG 98-01 examining chemoRT with or without the amifostine (Ethyol; MedImmune, Inc, Gaithersburg, MD), a cyto- and radioprotectant in locally advanced non-small cell lung cancer (n = 243). While amifostine did not significantly reduce severe esophagitis based on National Cancer Institute Common Toxicity Criteria and weekly physician dysphagia logs, swallowing dysfunction over time (based on patient diaries, the equivalent of Esophagitis Index) was significantly lower in the amifostine arm ( P = .03). Therefore, significant progress has been accomplished in our understanding of the basis of esophageal injury resulting from thoracic RT, and future effort may find other effective strategies to either minimize or eliminate esophagitis.
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PMID:Treatment-related esophagitis. 1601 37

Acute radiation-induced esophagitis includes all clinical symptoms (odynophagia, dysphagia) occurring within 90 days after thoracic irradiation start. Its severity can be graded using RTOG and CTCAE scales. The clinical risk factors are: age, female gender, initial performance status, pre-therapeutic body mass index, pre-therapeutic dysphagia, tumoral and nodal stage, delivered dose, accelerated hyperfractionned radiotherapy, concomitant association of chemotherapy to radiotherapy and response to the treatment. The dosimetric parameters predictive of esophagitis are: mean dose, V(20Gy), V(30Gy), V(40Gy), V(45Gy) and V(50Gy). Amifostine is the only drug to have a proven radioprotective efficacy (evidence level C, ESMO recommendation grade III). The medical management of esophagitis associates a diet excluding irritant food, medication against gastroesophageal reflux, analgesic treatment according to the WHO scale and management of dehydration and denutrition by enteral feeding.
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PMID:[Esophageal toxicity of radiation therapy: clinical risk factors and management]. 2292 86