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 combination of cisplatin and cytosine arabinoside has been shown in experimental models to be synergistic. We conducted a pilot study of cytosine arabinoside and cisplatin in unresectable or metastatic cancer of the esophagus in five patients and found significant activity, also on visceral metastasis. Therefore, we decided to examine this combination in the neoadjuvant setting. Since January 1989, eight patients with squamous cell carcinoma esophageal cancer were treated with two cycles of cytosine arabinoside (50 mg/m2) by continuous infusion for 4 days and by cisplatin (100 mg/m2) on the 5th day. Their ages ranged from 54-79 years. One patient had Stage I, three had Stage II, and four had Stage III disease. Responses assessed by endoscopy and computed tomographic (CT) scan prior to surgery were three with partial response, three with minor response, and two with no response. Only six patients were surgically resectable after chemotherapy. Toxicity consisted of grade 3 (one patient) and grade 4 (two patients) neutropenia, grade 3 (three patients) anemia, and grade 3 (two patients) and grade 4 (three patients) thrombocytopenia. All patients had subjective improvement of dysphagia 4 weeks after chemotherapy. Median survival of the whole group was 7.5 months. We concluded that there was no evidence of synergy of these drugs given in this manner in esophageal carcinoma since the response rate was no different from that achieved with cisplatin alone.
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PMID:Neoadjuvant chemotherapy with cytosine arabinoside by continuous infusion and cisplatin for resectable squamous cell carcinoma of the esophagus. 159 82

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.
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PMID:Fatal encephalitis in a patient with chronic graft-versus-host disease. 239 Jun 33

Twenty-one consecutive patients with squamous cell carcinoma of the esophagus (EC) were referred, with advanced Stage III disease in nine patients, severe pulmonary/cardiac disease in five patients, and postsurgical recurrences or metastatic disease in seven patients. They were treated with one to four courses of 5-fluorouracil (5-FU) + mitomycin C, alternating with 5-FU + cisplatin (5-FU: 1,000 mg/m2/24 X 96-h infusion; Mitomycin C: 10 mg/m2 i.v.; cisplatin: 75 mg/m2 i.v.) simultaneously with 3,000-5,000 cGy of local radiotherapy (RT) in 3.5-5.5 weeks. These doses of chemotherapy (CT) and RT were generally well tolerated except for prolonged thrombocytopenia in two patients, pancytopenia in one, pulmonary fibrosis in one, and acute renal failure in one. Six patients were alive and free of disease 8-40 months (median, 16 months; mean, 21.5 months) after initiation of treatment. Two additional patients died of unrelated causes without evidence of viable disease at autopsy. Our experience confirms the rapid and sustained palliation of dysphagia and pain obtained within 7-14 days after initiation of treatment. Mean survival of patients receiving one to two courses of CT and less than 4,000 cGy RT was 3.4 months compared to 16 months in patients receiving more than 2 courses of CT with RT. Five of six patients who are alive and free of disease received 4,000 cGy or greater. This experience suggests that escalated and concurrent doses of RT (greater than 4,000 cGy) and CT (three to four cycles) are tolerated with acceptable morbidity and could provide good palliation and sometimes prolonged disease-free status in those patients with EC who are considered inoperable because of advanced disease or medical reasons.
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PMID:Inoperable esophageal carcinoma: results of aggressive synchronous radiotherapy and chemotherapy. A pilot study. 244 91

Between October 1980 and December 1985, 50 patients with esophageal cancer were treated with combined radiotherapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin C). Thirty patients with stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 h) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Twenty patients received palliative treatment (5,000 cGy plus chemotherapy) for stage III or IV disease (extraesophageal spread or distant metastases). All patients treated in this program had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Of the 30 definitively treated patients, 23 had squamous cell cancer, while seven had adenocarcinoma. Follow-up ranged from 6 months to 63 months. The complete response rate at 1 to 3 months following completion of treatment was 87% (26 of 30) documented by barium swallow and endoscopy (+/- biopsy). The actuarially determined local relapse-free rate at 1 year and beyond was 73%, and the actuarial survivals at 1, 2, and 5 years were 68%, 47%, and 32%, respectively. Of the 20 palliatively treated patients, ten had squamous cell carcinoma, eight had adenocarcinoma, and two had undifferentiated carcinoma. Seventeen patients were evaluable for freedom from dysphagia 1 or more months following completion of treatment. Eighty-two percent of evaluable patients (14 of 17) had no dysphagia posttreatment, while 64% (11 of 17) remained free of dysphagia until death or last follow-up, emphasizing the significant local control of those patients. The median survival for this group was 8 months. Treatment was well tolerated, and acute toxicity included esophagitis, stomatitis, oral candidiasis, and hematologic toxicities of thrombocytopenia and neutropenia. Late toxicities were predominantly manifested as a mild to moderate benign stricture, which required dilatation in four patients. One patient developed a perforation into the mediastinum in the absence of tumor, while two patients with persistent local disease developed tracheoesophageal fistula, and radiation pneumonitis was observed in two patients. This combination of radiation therapy with infusional 5-FU and mitomycin C is an effective and relatively well-tolerated regimen in the treatment of esophageal cancer. Surgical resection may not be necessary when high-dose radiation and chemotherapy are used.
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PMID:Nonsurgical management of esophageal cancer: report of a study of combined radiotherapy and chemotherapy. 244 31

Single-agent therapy with paclitaxel is effective against both squamous cell carcinoma and adenocarcinoma of the oesophagus. However, only limited data are available on the combination of paclitaxel with other cytotoxic drugs in this entity. Patients with unresectable stage III, recurrent or metastatic tumours were treated in a multicentre setting with paclitaxel 90 mg m(-2) given over 3 h intravenously, followed by cisplatin 50 mg m(-2). The courses were repeated every 14 days. Twenty patients with squamous cell carcinoma or adenocarcinoma of the oesophagus were evaluable for response. The overall remission rate was 40% (8/20), including 15% (3/20) clinically complete responses. Clinical benefit response, defined as relief of dysphagia and/or significant gain in weight, was achieved in 70% of the patients. Neutropenia of CTC grade 3 occurred only in 10% of the patients; no grade 4 neutropenia and no severe thrombocytopenia was encountered. CTC grade 4 neurotoxicity was seen in 5% of patients. Cisplatin/paclitaxel administered every 14 days, was effective in patients with poor prognosis oesophageal cancer and toxicity was acceptable.
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PMID:Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. 971 36

A total of 30 with good prognosis small cell lung cancer were treated with a modified 'ICE' (ifosfamide, carboplatin and etoposide) chemotherapy regimen in an attempt to achieve a high response rate with less toxicity than is seen with the full 'ICE' regimen. This was given every 4 weeks for a maximum of six cycles. In total 25 patients (83%, 95% CI (70-97%)) experienced a partial or complete response at some stage of their treatment. Of these patients, 12 (40%, 95% CI (22-58%)) showed a complete response. A total of 19 patients (63%) had to have their dose reduced and/or delayed at some point due to toxicity. Nadir blood counts showed that 19 patients (63%, 95% CI (46-81%)) had WHO grade 3 or 4 thrombocytopenia, and 24 (86%, 95% CI (73-99%)) had grade 3 or 4 neutropenia. A total of 17 patients (53%) completed six cycles of chemotherapy. In total 3 patients died during treatment all due to treatment-related complications. Median survival was 12.6 months (95% CI (11.6, 14.7 months)). Nausea, vomiting, dysphagia, activity, mood and overall condition, as recorded using daily diary cards, were worse at the beginning of each chemotherapy cycle. Both response rates and survival were clinically acceptable. However, neutropenia and thrombocytopenia, although reduced from rates reported with the full ICE regimen, were still high. A prospective randomised controlled trial is now needed to assess this regimen in more detail.
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PMID:Modified ice study: a phase II study of an intensive, modified ICE regimen (ifosfamide, carboplatin and etoposide) in patients with better prognosis, small cell lung cancer. 982 45

Preoperative concurrent chemotherapy and radiotherapy can be highly effective but are often associated with significant rates of morbidity and even mortality. We studied the toxicity of continuous infusion of 5-fluorouracil (5-FU) and weekly paclitaxel combined with radiotherapy. Patients had histologic proof of local-regional carcinoma of the esophagus or gastroesophageal (GE) junction, a Karnofsky performance status of 70 or greater, and normal liver, renal, and bone marrow functions. Chemotherapy consisted of continuous infusion of 5-FU (300 mg/m2/d) for 5 days a week for 5 weeks, plus paclitaxel (45 mg/m2) given during 3 hours every week for 5 weeks. Based on the tumor location and its resectability, the total dose of concurrent radiation varied between 45 Gy and 50.4 Gy. Nine men and one woman, with a median age of 61 years, were evaluated. One had GE junction cancer, six had distal esophageal cancer, and three had midesophageal cancer. Weight loss, nausea, vomiting, and dysphagia of grades I and II were noted. The hematologic toxicity was mild. No patients required transfusion. There was no leukopenia or thrombocytopenia. None of the patients was hospitalized during chemoradiation; all patients completed treatment as outpatients. Five patients had subsequent surgical resections: one had a pathologically complete response, and two had a partial response (>90% necrosis). Continuous infusion of 5-FU plus paclitaxel given concurrently with radiotherapy was well tolerated. We plan to study this regimen further in upper gastrointestinal cancers.
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PMID:Pilot study of concurrent 5-fluorouracil/paclitaxel plus radiotherapy in patients with carcinoma of the esophagus and gastroesophageal junction. 1123 59

To improve the efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in metastatic esophageal cancer, we designed a new therapeutic schedule, the HLFP regimen. 42 patients with metastatic oesophageal adenocarcinoma (n=10) or squamous cell carcinoma (n=32) were prospectively enrolled in the study. All had bidimensionally measurable disease. The HLFP regimen consisted of twice-monthly oral administration of hydroxyurea 1 g/m(2) on days 0, 1 and 2; a 2-h infusion of leucovorin 200 mg/m(2) and a bolus of 5-FU 400 mg/m(2) followed by a 22-h infusion of 5-FU 600 mg/m(2) on days 1 and 2; and, every two cycles, 80 mg/m(2) cisplatin on day 3. Relief of dysphagia and other symptoms were monitored, together with body weight changes. Major objective responses were observed in 24 patients (57%, 95% Confidence Interval (CI): 42-72%), including four complete responses (10%). The median progression-free survival and overall survival times were 8 and 12.7 months, respectively. Weight gain was observed in 48% of patients, and dysphagia improved in 76%. Grade 3-4 toxicity occurred in 40% of patients, with grade 4 neutropenia in 12% and grade 3 thrombocytopenia, vomiting and diarrhoea in 7-9% of patients. There were no treatment-related deaths. These results suggest that the HLFP regimen is an active and well-tolerated chemotherapy for metastatic oesophageal carcinoma.
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PMID:Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer. 1191 43

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

We report the case of a 72-year-old lady who presented with fatigue and bruising. Initial investigations were compatible with iron deficiency anaemia and idiopathic thrombocytopenic purpura (ITP). The anaemia and recent heartburn symptoms led to endoscopy, which revealed an extensive oesophageal squamous cell carcinoma. The tumour was inoperable due to local extension and the patient was not deemed fit enough for aggressive chemotherapy. A course of radical local radiotherapy was given. The patient's ITP, which had initially been responsive to high-dose intravenous immunoglobulin, subsequently became refractory to all therapeutic modalities. The patient developed significant dysphagia but therapeutic options were limited due to her severe thrombocytopenia. The patient eventually died from a combination of gastrointestinal and intrapulmonary haemorrhage. This case is of interest for two reasons. First, the development of refractory ITP appeared to mirror the progression of the carcinoma, and to our knowledge this is the first case of ITP associated with oesophageal carcinoma. Second, despite recent endoscopic advances in palliating oesophageal tumours, this case highlights the difficulties that can still occur.
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PMID:Oesophageal carcinoma and refractory idiopathic thrombocytopenic purpura: a challenging combination. 1525 82


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