Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combination of cisplatin and hyperfractionated external beam irradiation (HEBI), followed by salvage surgery when indicated, was evaluated in patients with advanced stage squamous cell carcinoma of the head and neck. Thirty patients with stage III (n = 5) or IV (n = 25) disease received intravenous cisplatin 100 mg/m2 by 6-hour continuous infusion on days 1, 21, and 42 of HEBI. Radiation fractions of 110 cGy were given twice daily, separated by 4 to 6 hours, beginning within 12 hours after cisplatin delivery. Doses to the primary site ranged from 60 to 76.35 Gy (median: 72.3 Gy), with 60 to 74 Gy to nodal sites. Follow-up ranged from 4 to 28 months (median: 19 months). Clinical complete response of the primary site was seen in 27 of 29 patients (93%), and complete clinical clearance of adenopathy in 20 of 26 (76%). A second biopsy 6 to 8 weeks after completion of treatment showed residual disease in both the primary and nodal sites in three patients, and in only the primary site in one patient. Four patients with persistent adenopathy had pathologic confirmation at surgery. Four patients had recurrence after negative biopsy results 6 to 9 months after treatment biopsy. At present, with median follow-up of 19 months, eight patients (26%) have died secondary to uncontrolled primary or nodal disease. Two patients have died of nonrelated causes. Overall, 10 of 30 patients (66%) remain alive with no evidence of disease. Mucositis and weight loss were the most common side effects of treatment. Seven patients developed significant xerostomia, and four have cisplatin-related hearing loss requiring amplification. The early evidence of excellent response (89% pathologic complete response of primary sites; 78% complete response of nodal sites), coupled with acceptable treatment morbidity, warrants further study of this approach.
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PMID:Concomitant cisplatin and hyperfractionated external beam irradiation for advanced malignancy of the head and neck. 195 96

From 1976 to 1987, 98 patients affected with nasopharyngeal carcinoma were observed at the Oncology Center, Trento, Italy. Eighty of them were treated with radical radiation therapy (average total dose: 6432 Gy, range: 5500-7400 Gy) on primary tumor and positive neck nodes. The clinically negative neck received 5000 Gy. Each dose ranged from 180 to 250 Gy. Fifty-nine patients were treated with the split-course technique with an interval of about 15 days after receiving 4000 cGy. The patients were 60 males and 20 females, their age ranging 17-81 years (mean: 57 years). Histology diagnosed squamous cell carcinoma in 15 cases and undifferentiated carcinoma in 65 cases. All patients were staged according to TNM (UICC, 1978) criteria. Ten patients were stage I/II. Complete local control was obtained in 81.3% of cases. Actuarial global survival at 10 years was 52%, actuarial relapse-free survival was 49%. Mean follow-up is 33 months (range: 4-122 months). Squamous cell carcinoma at histology and advanced nodal involvement (N2-N3) were negative prognostic factors. Six patients had a relapse in the nasopharynx and 5 in the neck; the incidence of distant failures was 20%. The most frequent mid-/long-term side-effect was xerostomia.
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PMID:[Radical radiation therapy of carcinoma of the rhinopharynx: analysis of 80 cases]. 228 Nov 76

The two anticholinergics, atropine and glycopyrrolate, were used for premedication and as an adjunct to reversal of residual neuromuscular block in a double-blind study. Glycopyrrolate, being about twice as potent as atropine in the clinical situation, was used in half the dosage of atropine. When used for premedication, no difference was found between the drugs concerning patients complaining of dry mouth, but more patients in the glycopyrrolate group had a gastric juice pH greater than 2.5 compared to the atropine group (not statistically different). The reversal mixture consisted of necostigmine 2.5 mg with either atropine 1 mg or glycopyrrolate 0.5 mg. The heart rate response between 2 and 10 min after injecting the reversal mixture was statistically significant (P ranged from 0.0001 to 0.05), the atropine group showing the most marked decrease: 18% in the atropine group had sinus bradycardia compared to 5% in the glycopyrrolate group: 34% in the atropine group exhibited arrhythmias compared to 10% in the glycopyrrolate group, the most common form being a nodal rhythm in both groups. More patients in the atropine group had "excessive" oropharyngeal secretions (more than 2 ml) when extubated (P less than 0.05). The postoperative assessment showed little difference in the two groups, apart from a lower incidence of nausea and vomiting in the atropine group (not statistically different). The study shows that the use of glycopyrrolate was associated with a more stable cardiovascular system, fewer arrhythmias and superior control of oropharyngeal secretions at the time of reversal.
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PMID:A comparison of atropine and glycopyrrolate in anaesthetic practice. 715 72

This study documents dosage to radiation sensitive organs/structures located outside the radiotherapeutic target volume for four treatment situations: (a) head and neck, (b) brain (pituitary and temporal lobe), (c) breast and (d) pelvis. Clinically relevant treatment fields were simulated on a tissue-equivalent anthropomorphic phantom and subsequently irradiated with Cobalt-60 gamma rays, 6- and 18-MV x-ray beams. Thermoluminescent dosimeters and diodes were used to measure absorbed dose. The head and neck treatment resulted in significant doses of radiation to the lens and thyroid gland. The total treatment lens dose (300-400 cGy) could be cataractogenic while measured thyroid doses (1000-8000 cGy) have the potential of causing chemical hypothyroidism, thyroid neoplasms, Graves' disease and hyperparathyroidism. Total treatment retinal (400-700cGy) and pituitary (460-1000 cGy) doses are below that considered capable of producing chronic disease. The pituitary treatment studied consisted of various size parallel opposed lateral and vertex fields (4 x 4 through 8 x 8 cm). The lens dose (40-200 cGy) with all field sizes is below those of clinical concern. Parotid doses (130-1200 cGy) and thyroid doses (350-600 cGy) are in a range where temporary xerostomia (parotid) and thyroid neoplasia development are a reasonable possibility. The retinal dose (4000 cGy) from the largest field size (8 x 8 cm2) is in the range where retinopathy has been reported. The left temporal lobe treatment also used parallel opposed lateral and vertex fields (7 x 7 and 10 x 10 cm). Doses to the pituitary gland (5200-6200 cGy), both parotids (200-6900 cGy), left lens (200-300 cGy) and left retina (1700-4500 cGy) are capable of causing significant future clinical problems. Right-sided structures received insignificant doses. Secondary malignancies could result from measured total treatment thyroid doses (670-980 cGy). Analysis of three breast/chest wall and regional nodal irradiation techniques demonstrated a 25-50% decrease in secondary lung dose with use of independent collimation compared to use of custom alloy blocking material. However, it is unlikely that a reduction in secondary dose of this magnitude would reduce the risk of treatment sequellae. In four-field "box" pelvic irradiation, secondary testes dose may result in temporary (clamshell shield) or permanent azoospermia, but is unlikely to impair androgen production.
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PMID:Doses to radiation sensitive organs and structures located outside the radiotherapeutic target volume for four treatment situations. 840 17

Amongst the patients attending our combined oral medicine/rheumatology clinic, we have identified a subset presenting with xerostomia due to non-specific sialadenitis, who also suffer from generalized nodal osteoarthritis (NOA). We have called this combination SOX syndrome: sialadenitis, osteoarthritis and xerostomia. In this study, we have examined the characteristics of these patients clinically and histologically, and then determined the prevalence of SOX syndrome in patients with NOA compared to healthy age-matched controls. Patients were obtained from rheumatology clinics and a local old people's home. The series consisted of 35 patients with NOA and 18 age- and sex-matched controls without evidence of NOA or inflammatory rheumatic disease. There was no significant difference in age and sex between the two groups. None were on drugs known to induce xerostomia. The subjects were assessed for whole salivary, parotid saliva and lacrimal flow, autoantibodies, rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR). The whole saliva flow (mean +/- 95% CI) was 0.32 +/- 0.07 ml/min for the NOA group and 0.54 +/- 0.17 ml/min for the control group. The difference is statistically significant (P < 0.05, two-tailed Student's t-test). No statistically significant difference was found in the parotid and lacrimal flow rates of NOA and controls. Nine of the 35 NOA patients had reduced whole salivary flow (normal range > 0.02 ml/min) compared with only one out of 18 in the control group (P > 0.05, chi 2 test). All NOA patients with xerostomia and reduced whole salivary flow were RF, anti-Ro and anti-La negative, and had a normal ESR. Thus, 25% of subjects with NOA had clinical and laboratory features of SOX syndrome, suggesting that this is a defined disease entity.
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PMID:Chronic sialadenitis in patients with nodal osteoarthritis. 944 93

We studied target volume coverage and normal tissue sparing of serial tomotherapy intensity modulated radiation therapy (IMRT) and fixed-field IMRT for nasopharyngeal carcinoma (NPC), as compared with those of conventional beam arrangements. Twelve patients with NPC (T2-4N1-3M0) at Mallinckrodt Institute of Radiology underwent computed tomography simulation. Images were then transferred to a virtual simulation workstation computer for target contouring. Target gross tumor volumes (GTV) were primary nasopharyngeal tumor (GTV(NP)) with a prescription of 70 Gy, grossly enlarged cervical nodes (GTV(LN)) with a prescription of 70 Gy, and the uninvolved cervical lymphatics [designated as the clinical tumor volume (CTV)] with a prescription of 60 Gy. Critical organs, including the parotid gland, spinal cord, brain stem, mandible, and pituitary gland, were also delineated. Conventional beam arrangements were designed following the guidelines of Intergroup (SWOG, RTOG, ECOG) NPC Study 0099 in which the dose was prescribed to the central axis and the target volumes were aimed to receive the prescribed dose +/- 10%. Similar dosimetric criteria were used to assess the target volume coverage capability of IMRT. Serial tomotherapy IMRT was planned using a 0.86-cm wide multivane collimator, while a dynamic multileaf collimator system with five equally spaced fixed gantry angles was designated for fixed-beam IMRT. The fractional volume of each critical organ that received a certain predefined threshold dose was obtained from dose-volume histograms of each organ in either the three-dimensional or IMRT treatment planning computer systems. Statistical analysis (paired t-test) was used to examine statistical significance. We found that serial tomotherapy achieved similar target volume coverage as conventional techniques (97.8 +/- 2.3% vs. 98.9 +/- 1.3%). The static-field IMRT technique (five equally spaced fields) was inferior, with 92.1 +/- 8.6% fractional GTV(NP) receiving 70 Gy +/- 10% dose (P < 0.05). However, GTV(LN) coverage of 70 Gy was significantly better with both IMRT techniques (96.1 +/- 3.2%, 87.7 +/- 10.6%, and 42.2 +/- 21% for tomotherapy, fixed-field IMRT, and conventional therapy, respectively). CTV coverage of 60 Gy was also significantly better with the IMRT techniques. Parotid gland sparing was quantified by evaluating the fractional volume of parotid gland receiving more than 30 Gy; 66.6 +/- 15%, 48.3 +/- 4%, and 93 +/- 10% of the parotid volume received more than 30 Gy using tomotherapy, fixed-field IMRT, and conventional therapy, respectively (P < 0.05). Fixed-field IMRT technique had the best parotid-sparing effect despite less desirable target coverage. The pituitary gland, mandible, spinal cord, and brain stem were also better spared by both IMRT techniques. These encouraging dosimetric results substantiate the theoretical advantage of inverse-planning IMRT in the management of NPC. We showed that target coverage of the primary tumor was maintained and nodal coverage was improved, as compared with conventional beam arrangements. The ability of IMRT to spare the parotid glands is exciting, and a prospective clinical study is currently underway at our institution to address the optimal parotid dose-volume needs to be spared to prevent xerostomia and to improve the quality of life in patients with NPC.
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PMID:Comparison of intensity modulated radiation therapy (IMRT) treatment techniques for nasopharyngeal carcinoma. 1129 Oct 96

Organ preservation in patients with head and neck cancer can be achieved using concomitant chemoradiation protocols. Critical tissues can be spared using highly conformal radiation therapy techniques and/or radiation protectors. With three-dimensional conformal radiation therapy (3DCRT) tight target definitions of the primary tumor and neck nodal levels are mandatory. In 2000, a clinical trial for advanced-stage head and neck squamous cell carcinoma was initiated in Rotterdam, The Netherlands. Patients are treated with paclitaxel administered concomitantly with 3DCRT and randomized to receive subcutaneous (SC) amifostine or no amifostine. Those in the radioprotectant arm received amifostine 500 mg SC before each radiation therapy (RT) fraction. This article presents early findings on toxicity. Acute toxicity is evaluated according to Radiation Therapy Oncology Group criteria. Xerostomia was scored subjectively and by whole saliva measurements. Neck nodal levels were delineated in accordance with previously published computed tomography (CT)-based guidelines developed in Rotterdam. Forty-one patients are the subject of this report. In patients treated with amifostine, mucositis and dysphagia took longer to resolve than with conventional RT schedules. No difference in objective and subjective evaluation of xerostomia was seen between treatment arms. So far in this ongoing study, no advantage of SC amifostine has been detected. This might be because of the toxicity of the concomitant treatment itself, the dose of amifostine, the route of administration, or the insufficient sparing of critical structures by 3DCRT. These early findings and the ongoing development of better tissue-sparing techniques with more accurate CT-based target delineation protocols and intensity-modulated radiation therapy (IMRT) are discussed.
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PMID:Tools for optimal tissue sparing in concomitant chemoradiation of advanced head and neck cancer: subcutaneous amifostine and computed tomography-based target delineation. 1257 48

Intensity-modulated radiotherapy (IMRT) has been available at Peter MaCallum Cancer Centre (PMCC) since November 2000. The present report illustrates two cases of our early experience with IMRT. Case 1 is a 66-year-old man with a T(1)N(2)M(0) nasopharyngeal carcinoma treated with chemo-radiotherapy using parotid-sparing IMRT. Fourteen months following treatment he remains in complete remission, with salivary function assessed using a xerostomia-specific quality of life questionnaire, having returned to near pretreatment levels by 12 months. Case 2 is a 70-year-old man with a T(4)N(0)M(0) base of tongue squamous cell carcinoma treated with chemo-radiotherapy after refusing radical surgery. He had received subtotal nodal irradiation to 36 Gy in 1994 for Hodgkins disease stage IIA. A radical dose was still achievable despite previous irradiation without exceeding unacceptable spinal cord dose with IMRT. He remains in complete remission 14 months from his initial presentation without evidence of neurological toxicity. Intensity-modulated radiotherapy allows sparing of critical normal structures in the head and neck without compromising dose to the tumour. It is, therefore, desirable for several clinical applications and essential in some, if unacceptable compromises are not to be made.
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PMID:Intensity-modulated radiotherapy: examples of its utility in head and neck cancer. 1502 21

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

Intensity modulated radiation therapy (IMRT) allows for relative parotid salivary gland sparing for patients undergoing treatment for head and neck squamous cell cancer, but is less reliable for sparing the submandibular glands. Cytoprotection with amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) has been shown to decrease rates of acute and late xerostomia in patients undergoing radiation therapy for head and neck squamous cell cancer. The addition of amifostine to IMRT may augment parotid salivary sparing, and add submandibular/sublingual, and minor salivary gland sparing resulting in greater salivary flow rates and a more physiologic saliva. Eligible patients include those slated to receive definitive IMRT for early oropharynx cancer or postoperative RT, both without chemotherapy, for more advanced cancers. These include T1, T2 and favorable T3 (favorable, exophytic), N0-2b (small volume) M0 oropharynx cancers who are to receive bilateral neck RT. Postoperative patients with nodal metastases, T3 and T4 primaries, perineural invasion, and lymphovascular invasion will be eligible. Patients will receive 30 to 33 fractions. Clinical target volume (CTV) 1 will receive 60 to 66 Gy, CTV2 will receive 60 Gy, and CTV3 will receive 54 to 57 Gy. The mean dose goal for the parotid gland is 25 Gy. Patients will receive fixed-dose amifostine 500 mg subcutaneously 30 to 60 minutes before each radiation fraction. Subjective xerostomia questionnaires will be administered. Whole mouth and individual major salivary gland stimulated and unstimulated saliva will be collected before and after therapy at 6 weeks, 6 and 12 months. Xerostomia outcomes will be correlated with salivary dose volume histogram data. Accrual has not yet begun. The results of this study will give an indication of the objective and subjective benefit of combined IMRT physical parotid salivary sparing and amifostine chemical cytoprotection for combined salivary gland sparing and reduction in the rate of xerostomia in patients undergoing IMRT for head and neck squamous cell cancer.
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PMID:A phase II study to assess the efficacy of amifostine for submandibular/sublingual salivary sparing during the treatment of head and neck cancer with intensity modulated radiation therapy for parotid salivary sparing. 1572 19


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