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PubMed1987

Cervical carcinoma: prognosis in younger patients.

Retrospective analysis of 2870 patients with invasive carcinoma of the cervix treated by radiotherapy from 1971 to 1978 showed that the prognosis for younger patients (defined as either under 35 or under 40) was better than that for older age groups, but young patients presented with earlier disease. When the effect of stage on prognosis was also considered the improved survival of patients under 35 was confirmed, although the result was of only borderline significance. The better survival of younger patients was particularly noticeable for stage IB disease, the corrected five year survival of those under 35 being 93% compared with 79% for those over 35. On the basis of this analysis and a review of previous reports it is concluded that age alone is a poor indicator of prognosis and should not be used as an indication for adjuvant treatment. There is no evidence in this series of an aggressive form of cervical carcinoma in younger patients during the 1970s.

Adult↗
PubMed2003

Prognosis of angina with and without a diagnosis: 11 year follow up in the Whitehall II prospective cohort study.

OBJECTIVE: To investigate the prognosis of angina among people with and without diagnosis by a doctor and an abnormal cardiovascular test result. DESIGN: Prospective cohort study with a median follow up of 11 years. SETTING: 20 civil service departments originally located in London. PARTICIPANTS: 10 308 civil servants aged 35-55 years at baseline. MAIN OUTCOME MEASURES: Recurrent reports of angina; quality of life (SF-36 physical functioning); non-fatal myocardial infarction; death from any cause (n = 344). RESULTS: 1158 (11.4%) participants developed angina, and 813 (70%) had no evidence of diagnosis by a doctor at the time of the initial report. Participants without a diagnosis had an increased risk of impaired physical functioning (age and sex adjusted odds ratio of 2.36 (95% confidence interval 1.91 to 2.90)) compared with those who had neither angina nor myocardial infarction throughout follow up. Among reported cases of angina without a diagnosis, the 15.5% with an abnormality on a study electrocardiogram had an increased risk of death (hazard ratio 2.37 (1.16 to 4.87)). These effects were similar in magnitude to those in participants with a diagnosis of angina. CONCLUSION: Undiagnosed angina was common and had an adverse impact on prognosis comparable to that of diagnosed angina, particularly among people with electrocardiographic abnormalities. Efforts to improve prognosis among people with angina should take account of this submerged clinical iceberg.

Adult↗
PubMed1970

Long-term prognosis following ventricular fibrillation in acute ischaemic heart disease.

Of 160 patients who survived ventricular fibrillation complicating acute ischaemic heart disease, 80 had had a clinically mild coronary attack. Most of the long-term survivors had ventricular fibrillation within 24 hours of the onset of symptoms. The longterm prognosis of the survivors was similar to that of patients whose myocardial infarction was not complicated by ventricular fibrillation. Those patients who survived ventricular fibrillation which occurred within four hours of the onset of symptoms were younger, usually had had a mild coronary attack, and had the most favourable longterm prognosis. The number of episodes of ventricular fibrillation did not affect adversely the long-term prognosis. Of those who at the time of review were eligible to work, 86% were fit to work and 68% were actually at work.

Acute Disease↗
PubMed2002

Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma.

BACKGROUND: Although the prognosis in malignant resectable intraductal papillary mucinous tumours of the pancreas (IPMT) is often considered more favourable than for ordinary pancreatic ductal adenocarcinoma, the long term outcome remains ill defined. AIMS: To assess prognostic factors in patients with malignant IPMT after surgical resection, and to compare long term survival rates with those of patients surgically treated for ductal adenocarcinoma. METHODS: Seventy three patients underwent surgery for malignant IPMT in four French centres. Clinical, biochemical, and pathological features and follow up after resection were recorded. Patients with invasive malignant IPMT were matched with patients with pancreatic ductal adenocarcinoma, according to age and TNM stages; survival rates after resection were compared. RESULTS: Surgical treatment for IPMT were pancreaticoduodenectomy (n=46), distal (n=14), total (n=11), or segmentary (n=2) pancreatectomy. The operative mortality rate was 4%. IPMT corresponded to in situ (n=22) or invasive carcinoma (n=51). In the latter group, 17 had lymph node metastases. Overall median survival was 47 months. Five year survival rates in patients with in situ and invasive carcinoma were 88% and 36%, respectively. On univariate analysis, abdominal pain, preoperative high serum carbohydrate antigen 19.9 concentrations, caudal localisation, invasive carcinoma, lymph node metastases, peripancreatic extension, and malignant relapse were associated with a fatal outcome. Using multivariate analysis, lymph node metastases were the only prognostic factor (OR 7.5; 95% CI: 3.4 to 16.4). Overall five year survival rate was higher in patients with malignant invasive IPMT compared with those with pancreatic ductal carcinoma (36 v 21%, p=0.03), but was similar in the subset of stage II/III tumours. CONCLUSIONS: The prognosis of patients with resected in situ/invasive stage I malignant IPMT is excellent. In contrast, prognosis of locally advanced forms is as poor as in patients with pancreatic ductal adenocarcinoma.

Adenocarcinoma, Mucinous↗
PubMed2003

Prognosis for patients newly admitted to hospital with heart failure: survival trends in 12 220 index admissions in Leicestershire 1993-2001.

OBJECTIVE: To examine rates of, prognosis following, and the influences on first hospital admission with heart failure in Leicestershire during 1993-2001. DESIGN: Historical cohort study using record linked discharge and mortality data. SETTING: Leicestershire, England. PATIENTS: 12 220 individual patients newly hospitalised with heart failure between 1 April 1993 and 31 March 2001. MAIN OUTCOME MEASURES: 30 day and one year survival, temporal trends in survival, and the influence on prognosis of age, sex, comorbidity, social deprivation, and year of hospital admission. METHODS AND RESULTS: Between 1993/94 and 2000/01, rates of first hospitalisation increased by 62%, from 29 to 47/10 000 population, confined largely to those aged > 65 years. Rates did not increase after 1998. Median age at presentation increased from 74 years in 1993/94 to 77 years in 2000/01 for men but was unchanged (80 years) for women. Overall one and five year survival was 57% and 27%, respectively. There was a 43-45% increase in risk of death for each decade of age at admission and a 14-17% increase associated with male sex. There was a clear influence on outcome of comorbidity but no influence of social deprivation score. Both one month and one year survival were lower for patients whose first heart failure admission was concomitant with acute myocardial infarction. Between 1993/94 and 2000/01 postdischarge cardiovascular survival improved by 50% (p < 0.001). CONCLUSIONS: Rates of first hospital admission with heart failure reached a plateau in the late 1990s. Case fatality rates remain high and prognosis poor, in particular for those of increasing age, for men, and for patients with concomitant acute myocardial infarction. However, clear trends to improved survival were seen over this time.

Adult↗
PubMed2004

C Reactive protein, moderate alcohol consumption, and long term prognosis after successful coronary stenting: four year results from the GENERATION study.

OBJECTIVES: To determine the impact of moderate alcohol consumption on long term prognosis after successful coronary stenting, and whether it could be related to preprocedural plasma C reactive protein (CRP). DESIGN: Part of the prospectively designed GENERATION study which investigated the impact of several biochemical factors, including plasma CRP, on long term prognosis after coronary stenting. SETTING: Tertiary referral centre. PATIENTS: 483 consecutive patients with stable or unstable coronary artery disease who underwent successful coronary stenting and were followed for up to four years. Information about alcohol consumption was collected prospectively. INTERVENTIONS: Successful coronary stenting. MAIN OUTCOME MEASURES: The incidence of the composite end point of readmission to hospital for unstable angina, non-fatal myocardial infarction, or cardiac death, whichever occurred first. RESULTS: By the end of follow up the incidence of the composite end point was 22.8%. Patients with a baseline plasma CRP concentration of < 0.68 mg/dl (defined by ROC analysis) did not show any difference in the composite end point (p = 0.9) or its components, regardless of the amount of alcohol consumed during follow up. However, among patients with plasma CRP concentration of > or = 0.68 mg/dl, those who drank moderately had a lower incidence of the composite end point (p < 0.001) or its components. CONCLUSIONS: Moderate alcohol consumption may have a beneficial impact on the long term prognosis following successful coronary stenting. The extent of this effect is positively related to preprocedural inflammatory status. An anti-inflammatory action of moderate alcohol consumption cannot be excluded.

Alcohol Drinking↗
PubMed2005

Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain.

OBJECTIVE: To assess whether antibodies to human heat shock protein 60 (anti-huhsp60) or to mycobacterial heat shock protein 65 (anti-mhsp65) predict an adverse one year prognosis in patients admitted with acute cardiac chest pain. DESIGN: Prospective observational study. SETTING: Teaching hospital. PATIENTS: 588 consecutive emergency admissions of patients with acute chest pain of suspected cardiac origin. MAIN OUTCOME MEASURES: Anti-huhsp60 and anti-mhsp65 titres were assayed on samples drawn on the morning after admission. The end points after discharge were coronary heart disease death, non-fatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, angiogram, or readmission with further cardiac ischaemic chest pain. RESULTS: During follow up after discharge (mean of 304 days, range 1-788 days), 277 patients had at least one of the study outcomes. Patients with increased titres of anti-huhsp60 had an adverse prognosis (hazard ratio 1.56 (95% confidence interval 1.09 to 2.23) comparing highest versus lowest quartiles, p = 0.015). Anti-mhsp65 titres were not predictive. CONCLUSIONS: Patients admitted with acute cardiac chest pain and increased titres of anti-huhsp60 had an adverse one year prognosis.

Acute Disease↗
PubMed2006

Prognosis and prognostic factors in patients with hypertrophic cardiomyopathy in Japan: results from a nationwide study.

OBJECTIVE: To investigate prognosis and prognostic factors in patients with hypertrophic cardiomyopathy (HCM) in Japan. DESIGN: A nationwide epidemiological study. SETTING: Hospitals selected randomly from among all hospitals in Japan. PATIENTS: Clinical and epidemiological information for 2155 patients with HCM were collected in 1999. MAIN OUTCOME MEASURES: Patients were classified on the basis of baseline prognostic factors. Survival rates up to 5 years were calculated by Cox's proportional hazard model for 1605 patients. RESULTS: During the follow-up period, 241 deaths were recorded. The crude 5-year survival rate for the entire cohort was 86% (95% CI 84 to 88), and annual mortality ranged from 2.2% to 3.0%. A higher cardiothoracic ratio on chest x ray (HR 1.61; 95% CI 1.26 to 2.05, with 1 SD (6.2%) increase), a lower left ventricular ejection fraction (HR 1.42; 95% CI 1.20 to 1.69, with 1 SD (13%) decrease) and the presence of left bundle branch block (HR 3.14; 95% CI 1.28 to 7.71) were independently associated with a poorer prognosis, whereas the presence of apical hypertrophy at baseline (HR 0.58; 95%CI 0.36 to 0.92) predicted a better chance of survival. CONCLUSIONS: The nationwide survey of patients with hypertrophic cardiomyopathy yielded important information on its prognosis and prognostic factors. These observations afford, for the first time, a measure of risk stratification in patients with HCM in Japan.

Adult↗
PubMed2006

Prognosis of stable angina pectoris: why we need larger population studies with higher endpoint resolution.

The prognosis of angina was described as "unhappy" by the Framingham investigators and as little different from that of 1-year survivors of acute myocardial infarction. Yet recent clinical trials now report that angina has a good prognosis with adverse outcomes reduced to "normal levels". These disparate prognostic assessments may not be incompatible, applying as they do to population cohorts (Framingham) and selected participants in clinical trials. Comparisons between studies are further complicated by the absence of agreed case definitions for stable angina (contrast this with acute coronary syndromes). Our recent data show that for patients with recent onset symptoms attending chest pain clinics, angina remains a high-risk diagnosis and although many patients receive symptomatic benefit from revascularisation, prognosis is usually unaffected. This leaves little room for complacency and, with angina the commonest initial manifestation of coronary artery disease, there is the opportunity for early detection, risk stratification and treatment to modify outcomes. Meanwhile, larger population-based studies are needed to define the patient journey from earliest presentation through the various syndrome transitions to coronary or noncardiac death in order to increase understanding of the aetiological and prognostic differences between the different coronary disease phenotypes.

Age Distribution↗
PubMed2002

Should cancer patients be informed about their diagnosis and prognosis? Future doctors and lawyers differ.

OBJECTIVES: To compare attitudes of medical and law students toward informing a cancer patient about diagnosis and prognosis and to examine whether differences are related to different convictions about benefit or harm of information. SETTING AND DESIGN: Anonymous questionnaires were distributed to convenience samples of students at the University of Geneva containing four vignettes describing a cancer patient who wishes, or alternatively, who does not wish to be told the truth. PARTICIPANTS: One hundred and twenty seven medical students and 168 law students. MAIN OUTCOME MEASURES: Five point Likert scale of responses to the vignettes ranging from "certainly inform" to "certainly not inform" the patient. RESULTS: All medical students and 96% of law students favoured information about the diagnosis of cancer if the patient requests it. Seventy four per cent of medical students and 82% of law students favoured informing a cancer patient about his or her prognosis (p = 0.0003). Thirty five per cent of law students and 11.7% of medical students favoured telling about the diagnosis (p = 0.0004) and 25.6% of law students and 7% of medical students favoured telling about the prognosis (p < 0.0001) even if the patient had clearly expressed his wish not to be informed. Law students indicated significantly more often than medical students reasons to do with the patient's good, legal obligations, and the physician's obligation to tell the truth, and significantly less often than medical students that their attitude had been determined predominantly by respect for the autonomous choice of the patient. CONCLUSION: Differences in attitudes according to the type of case and the type of studies were related to convictions about the benefit or harm to the patient caused by being given information. The self reported reasons of future physicians and future lawyers are helpful when considering means to achieve a better acceptance of patients' right to know and not to know.

Adult↗
PubMed2005

Specific DWI lesion patterns predict prognosis after acute ischaemic stroke within the MCA territory.

BACKGROUND: Apart from diffusion-weighted imaging (DWI) lesion volume and diffusion-perfusion mismatching, there is limited information about neuroradiological predictors of early prognosis after an ischaemic stroke. This study sought to identify specific DWI lesion patterns that would help prediction of early prognosis of three different endpoints: unstable hospital course, recurrence of stroke, and poor neurological outcome at 90 days after ischaemic stroke. METHODS: A total of 426 patients with acute cerebral infarcts within the middle cerebral artery territory were prospectively studied. Using the DWI data the patients were divided into six groups (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts), and any recurrent strokes and prognosis over the following 90 days were recorded. RESULTS: DWI lesion pattern was a stronger and more consistent independent outcome predictor than DWI lesion volume. The specific DWI lesion patterns associated with each endpoint differed. An unstable hospital course was frequently observed in patients with internal border zone infarcts, whereas recurrent strokes after the index stroke were commoner in those who had small superficial infarcts (p<0.05 in both cases). Similarly, poor outcome after stroke was associated with older age, severe neurological deficits at admission, and a DWI lesion pattern showing internal border zone infarcts. CONCLUSIONS: The results of the present study indicate that the DWI lesion pattern may help in recognition of the likely differences in the early prognostic endpoints after ischaemic stroke, and DWI analysis may guide targeted interventions to prevent negative outcomes.

Acute Disease↗
PubMed1998

Guillain-Barré syndrome variants in Emilia-Romagna, Italy, 1992-3: incidence, clinical features, and prognosis. Emilia-Romagna Study Group on Clinical and Epidemiological Problems in Neurology.

OBJECTIVES: To estimate the incidence rate of Guillain-Barré syndrome variants in an unselected population and to describe their clinical features and prognosis. METHODS: A two year prospective multicentre study on the incidence and prognosis of Guillain-Barré syndrome was performed in Emilia-Romagna, northern Italy (3,909,512 inhabitants). A surveillance system was instituted within the study area, which comprised all the neurological departments, private and public general hospitals, and practising neurologists. The international classification of diseases (ICD) codes 357.XX (any peripheral neuropathy) of hospital discharges were also reviewed. RESULTS: Data were separately analysed for Miller Fisher syndrome and other Guillain-Barré syndrome variants. During the study period 18 patients with Guillain-Barré syndrome variants including seven with Miller Fisher syndrome were recruited; the incidence rates were 0.14/100000/year (95% confidence interval (95% CI) 0.07-0.25) for Guillain-Barré syndrome variants (excluding Miller Fisher syndrome) and 0.09/100000/year (95% CI 0.04-0.18) for Miller Fisher syndrome. Guillain-Barré syndrome variants alone (excluding Miller Fisher syndrome) accounted for 10.5% of total cases. Death and relapses were not found. Details of clinical, electrophysiological, and CSF findings of Guillain-Barré syndrome variants are provided. CONCLUSIONS: Guillain-Barré syndrome variants other than Miller Fisher syndrome, as obtained through a population based study, account for about 10% of total cases of Guillain-Barré syndrome and, as a whole, have a good prognosis. Their clinical features are heterogeneous; bifacial weakness (associated with other signs, mainly sensory disturbances) represents the most frequent finding.

Adolescent↗
PubMed2000

Prognosis of stroke in the south of Greece: 1 year mortality, functional outcome and its determinants: the Arcadia Stroke Registry.

OBJECTIVES: For Greece, data on incidence of stroke, type of stroke, and prognosis of stroke is limited. Recently, results on incidence of stroke were published. Here 1 year mortality, functional outcome after a first ever stroke, and determinants of the prognosis are described. METHODS: A population based registry was established in the Arcadia area, located in eastern central Peloponessos in southern Greece. Between 1 November 1993 and 31 October 1995, 555 patients with a first ever stroke were identified using information from death certificates, hospital records, public health centres and general practitioners. Extensive information on cardiovascular risk factors and stroke characteristics was obtained. After 1 year a modified Rankin score was determined in all surviving patients. RESULTS: After 1 year of follow up, 204 (36.8%) patients died. The probability of survival 1 year after stroke was higher for cerebral infarction than for intracerebral haemorrhage; 67.8% (95% confidence interval (95% CI) 64-72) and 46.4% (35-57), respectively. Of the survivors, 68.9% had either no symptoms or symptoms that would not interfere with their capacity to look after themselves (Rankin score 0 to 2). Increasing age and low Glasgow coma scale score were the most powerful predictors of death within 1 year (p<0.01), whereas increasing age, atrial fibrillation, and low Glasgow coma scale score were the most important predictors of functional outcome 1 year after a stroke (p<0.01). CONCLUSIONS: One year mortality from stroke in Greece is similar to that of other industrialised countries. The most important factors that affect the prognosis of a patient with a first ever stroke are increasing age, stroke severity, and atrial fibrillation.

Adolescent↗
PubMed1989

Correlations between histological type, clinical behaviour, and prognosis in thymoma.

Seventy four cases of thymoma were reclassified into three histological categories--cortical (30), medullary (9), and mixed (34) (the remaining patient had an intrathymic thymoma)--for an investigation of the relation between histological type, clinical behaviour, and long term prognosis. There were significant differences between the histological types in the frequency of myasthenia gravis and of the different tumour stages, the mean age of the patients, and prognosis. Myasthenia gravis occurred more commonly in patients with cortical (33%) and mixed thymoma (35%) than in patients with medullary thymoma (11%). Five, 10, 15, and 20 year actuarial survival was 100% for medullary thymoma; 85%, 76%, 65% and 65% respectively for mixed thymoma; and 52%, 45%, 45%, and 45% for cortical thymoma. Medullary thymoma is a benign tumour arising late in life and there was no mortality in this series after surgery alone. Cortical thymoma usually presented in middle age and must be regarded as malignant; mortality was 50% at five years despite a multidisciplinary approach, with surgery and postoperative radiotherapy in all patients and chemotherapy in selected cases. Mixed thymoma had a better prognosis than cortical thymoma, but must be regarded as potentially malignant. One third of the total patients had died by 10 years despite radical tumour resection.

Adolescent↗
PubMedDate not supplied

Revisiting "respiratory function in emphysema in relation to prognosis".

BACKGROUND: The 1956 paper by DV Bates, JMS Knott and RV Christie, "Respiratory function in emphysema in relation to prognosis" Quart J Med 1956;97:137-157 is largely reprinted with a commentary by the first author, Dr David Bates. Although the pathology of emphysema was well recognized at the time, the clinical diagnosis and assessment of its severity were known to be imprecise; physiological measurements assessing and following the clinical course had not been established. The study aimed to follow systematically a group of patients, selected by clinical criteria using standardized clinical and physiological techniques, over four years and correlate physiological and clinical changes in relation to prognosis and eventually to postmortem findings. Fifty-nine patients were recruited to an emphysema clinic at St Bartholomew's Hospital, London, England. Inclusion criteria were dyspnea without other causes and no cor pulmonale present. Patients' symptoms were assessed by a standardized questionnaire, and measurements were taken of lung volumes, maximal ventilatory volume, carbon monoxide diffusing capacity at rest, exercise and oxygen saturation by oximetry. During the four years of the study, 17 patients died (actuarial expected - four) and 13 presented with signs of pulmonary heart failure. All postmortem examinations (n=9) showed advanced emphysema. A seasonal variation in dyspnea was established (the period included the infamous 1952 London smog). Four patients improved, and the remainder were unchanged or deteriorated. Close relationships were shown between dyspnea and function results, particularly for the diffusing capacity of lungs for carbon monoxide (DLCO). A comparison among a group of patients with chronic bronchitis without dyspnea showed that the DLCO discriminated between them. A loss of the normal increase in DLCO during exercise was shown in emphysema. IMPORTANCE: The study showed the value of standardized clinical and physiological techniques in following chronic obstructive pulmonary disease patients, and of separating the effects of airflow obstruction from impaired gas exchange function. Impaired gas exchange was shown to be important in influencing prognosis.

History, 20th Century↗
PubMed2005

Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer.

Microarray analysis has been shown to improve risk stratification of breast cancer. Breast tumors analyzed by hierarchical clustering of expression patterns of "intrinsic" genes have been reported to subdivide into at least four molecular subtypes that are associated with distinct patient outcomes. Using a supervised method, a 70-gene expression profile has been identified that predicts the later appearance or absence of clinical metastasis in young breast cancer patients. Here, we show that distant metastases display both the same molecular breast cancer subtype as well as the 70-gene prognosis signature as their primary tumors. Our results suggest that the capacity to metastasize is an inherent feature of most breast cancers. Furthermore, our data imply that poor prognosis breast carcinomas classified either by the intrinsic gene set or the 70 prognosis genes represent distinct disease entities that seem sustained throughout the metastatic process.

Breast Neoplasms↗
PubMed2004

Carbonic anhydrase IX as a marker for poor prognosis in soft tissue sarcoma.

PURPOSE: Hypoxia is associated with malignant progression and poor outcome in several human tumors, including soft tissue sarcoma. Recent studies have suggested that carbonic anhydrase (CA) IX is an intrinsic marker of hypoxia, and that CA IX correlates with poor prognosis in several types of carcinoma. The aim of this study was to quantify the extent of CA IX expression and to investigate whether CA IX is a marker for poor prognosis in soft tissue sarcoma patients at high risk of developing metastasis. EXPERIMENTAL DESIGN: Archival paraffin-embedded blocks were retrieved from 47 patients with deep, large, high-grade soft tissue sarcoma. Sections from two separate and representative tumor areas were immunostained for CA IX, and the CA IX-positive area fraction was quantified by image analysis, excluding areas of normal stroma and necrosis that were identified from serial H&E-stained sections. Patients were then subject to survival analysis. RESULTS: CA IX-positive area fractions of viable tumor tissue varied significantly between tumors (range, 0-0.23; median, 0.004), with positive membranous CA IX staining in 66% (31 of 47) of the tumors. Patients with CA IX-positive tumors had a significantly lower disease-specific and overall survival than patients with CA IX-negative tumors (P = 0.033 and P = 0.044, respectively). CONCLUSIONS: These data suggest that CA IX, a potential intrinsic marker of hypoxia, predicts for poor prognosis in patients with deep, large, high-grade soft tissue sarcoma. Larger studies are required to determine whether CA IX has independent prognostic value in this group of tumors.

Adult↗
PubMed2004

Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, gemcitabine, and twice-daily radiation in patients with poor-prognosis cancer of the head and neck.

PURPOSE: We previously demonstrated high locoregional control, in patients with poor-prognosis head and neck cancer (HNC), using paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant hyperfractionated radiotherapy. In the present phase I trial, gemcitabine, a novel antimetabolite with strong radiation-enhancing activity, replaces hydroxyurea. We sought to determine the recommended phase II dose and clinical efficacy in poor-prognosis HNC patients. EXPERIMENTAL DESIGN: Seventy-two patients enrolled. Eligibility criteria included recurrent or second primary HNC, metastases or expected 2-year survival <20%. Chemoradiotherapy consisted of 5-fluorouracil, 600 mg/m(2)/d, for 5 days; paclitaxel, 100 mg/m(2) on Day 1; and concurrent 1.5 Gy twice-daily radiation for 5 days. Gemcitabine was dose escalated, 50-300 mg/m(2) on day 1. Cycles repeated every 14 days until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: neutropenic fever; grade > or =4 neutropenia or thrombocytopenia for >4 days; grade > or =4 mucositis or dermatitis for >7 days; or grade 3 toxicity necessitating chemotherapy dose reductions. Non-DLT dose reductions in 5-fluorouracil and/or paclitaxel were allowed. RESULTS: Seventy-nine percent of assessable patients experienced a clinical response. Five-year actuarial survival is 33.0%, and locoregional control is 61.4%. The recommended phase II dose of gemcitabine in this regimen is 100 mg/m(2) during cycles 1-5 (1 of 7 patients with DLT) or 200 mg/m(2) delivered only during cycles 3-5 (3 of 19 with DLT). Grades 3 and 4 mucositis (56 and 21%, respectively) and dermatitis (25 and 21%, respectively) were common. CONCLUSIONS: Gemcitabine, 5-fluorouracil, paclitaxel, and twice-daily radiation, delivered on alternating weeks, is active in patients with poor-prognosis HNC, although severe mucositis limits the clinical applicability of this regimen. Refinements in radiotherapy, including intensity-modulated radiation therapy, may improve the tolerance for this regimen.

Adolescent↗