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Photodynamic therapy for endobronchial malignant disease: a prospective fourteen-year study.

BACKGROUND: After intravenous injection, the photosensitizer dihematoporphyrin either is selectively retained in tumor cells. This photosensitizer absorbs 630 nm wavelength light energy and produces a singlet oxygen that destroys the tumor. Photodynamic therapy was performed on endobronchial tumors with the use of light generated by an argon dye laser system delivered through cylinder diffusing tip quartz fibers passed through the biopsy channel of a flexible endoscope. OBJECTIVES: Our objectives were to determine factors affecting survivals, benefits, and complications. METHODS: From 1982 to May 1996, photodynamic therapy was performed on 175 patients with endobronchial tumors. Sixteen had stage I disease, 9 stage II, 42 stage IIIA, 64 stage IIIB, and 44 stage IV. All were followed up until death or November 1996. RESULTS: Multivariate analysis of survival of the effects of age, sex, race, histologic features, Karnofsky Performance Status, and clinical stage showed the clinical stage (p < 0.0001) to be the most statistically significant factor. Sixteen patients with stage I disease had a 93% 5-year disease-related estimated survival. Median (months) survivals were as follows: stage I = not reached; stage II = 22.5; stage IIIA = 5.7; stage IIIB = 55; and stage IV = 5.0. Performance status does become significant when it reaches 50 but was not significant for stages I or II. CONCLUSIONS: Photodynamic therapy may be considered as an alternative treatment for patients under consideration for surgical treatment for stage I carcinoma in whom the risk of surgery is high. The length of palliation for patients with noncurative disease was equal to or better than that reported historically for most other treatment regimens.

Adenocarcinoma↗

Weekly irinotecan (CPT-11) in 5-FU heavily pretreated and poor-performance-status patients with advanced colorectal cancer.

Irinotecan (CPT-11) is an effective drug in patients with advanced colorectal cancer (CRC). Little is known about its efficacy and safety in previously treated patients with poor performance status. We prospectively evaluated the antitumor efficacy and safety of CPT-11 monotherapy in this setting. Thirty-four patients with poor performance status (Karnofsky score between 60 and 80) and/or progressing on one or more previous 5-FU-based chemotherapy lines for advanced colorectal adenocarcinoma were enrolled in this study. Treatment consisted of irinotecan (CPT-11) at 100 mg/m(2) administered as a 60-min iv infusion every week for four consecutive weeks followed by a 2-wk rest period until disease progression or unacceptable toxicity. The overall objective response rate (WHO criteria) for the 34 patients included was 20.6% [95% confidence interval (CI): 6.3%-34.9%]. Stable disease was obtained in 13 patients (38.2%) and 14 patients (41.2%) progressed. The median time to disease progression was 5.5 mo (range: 0.9-17.5) and the median survival was 8.3 mo (95% CI: 1.7-16.9). Overall, weekly CPT-11 was well tolerated with grade 3/4 neutropenia as the main hematological toxicity (11 patients: 32.4%; 14 infusions: 3.3%), and delayed diarrhea (10 patients: 29.4%; 16 infusions: 3.8%) as the main grade 3/4 non-hematological toxicity. In conclusion, weekly CPT-11 at 100 mg/m(2) for four consecutive weeks followed by a 2-wk rest period showed antitumor efficacy and may be safely administered to heavily pretreated patients with advanced colorectal cancer and a poor performance status. Weekly CPT-11 monotherapy may be considered as a therapeutic option for this population of patients.

Adenocarcinoma↗

Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE AND METHODS: The European Lung Cancer Working Party (ELCWP) performed a randomized trial with the primary end point to determine if maintenance chemotherapy with 12 courses of etoposide (120 mg/m2 on days 1 and 3) and vindesine (3 mg/m2 on day 3) could improve progression-free survival in small-cell lung cancer (SCLC) patients who responded to six courses of induction chemotherapy with ifosfamide, etoposide, and an anthracycline (doxorubicin or epirubicin). RESULTS: Among 235 eligible patients initially registered, 91 were randomized to receive maintenance therapy, including seven patients who were no longer responding. Among 84 randomized responders, progression-free survival was significantly improved (P = .003) by maintenance therapy, with median durations (maintenance v follow-up) of 25 versus 12 weeks after the second randomization, but survival was not significantly increased (P = .10), with median durations of 48 and 38 weeks. However, in a multi-variate analysis that took into account disease extent, maintenance therapy, Karnofsky performance status (PS), and absolute dose-intensity (ADI) of anthracycline given during induction, limited disease (LD) and maintenance were found to be independent positive predictors of survival. CONCLUSION: We conclude that maintenance chemotherapy in responding patients is beneficial in SCLC.

Adult↗

Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial.

BACKGROUND: The aim of the current prospective, randomized control study was to investigate the effect of dietary omega-3 polyunsaturated fatty acids plus vitamin E on the immune status and survival of well-nourished and malnourished patients with generalized malignancy. METHODS: Sixty patients with generalized solid tumors were randomized to receive dietary supplementation with either fish oil (18 g of omega-3 polyunsaturated fatty acids, PUFA) or placebo daily until death. Each group included 15 well-nourished and 15 malnourished patients. The authors measured total T cells, T-helper cells, T-suppressor cells, natural killer cells, and the synthesis of interleukin-1, interleukin-6, and tumor necrosis factor by peripheral blood mononuclear cells before and on Day 40 of fish oil supplementation. Karnofsky performance status, nutritional state, and survival were also estimated. RESULTS: The ratio of T-helper cells to T-suppressor cells was significantly lower in malnourished patients. Omega-3 PUFA had a considerable immunomodulating effect by increasing this ratio in the subgroup of malnourished patients. There were no significant differences in cytokine production among the various groups, except for a decrease in tumor necrosis factor production in malnourished cancer patients, which was restored by omega-3 fatty acids. The mean survival was significantly higher for the subgroup of well-nourished patients in both groups, whereas omega-3 fatty acids prolonged the survival of all the patients. CONCLUSIONS: Malnutrition appears to be an important predictor of survival for patients with end stage malignant disease. Omega-3 polyunsaturated fatty acids had a significant immunomodulating effect and seemed to prolong the survival of malnourished patients with generalized malignancy.

Adjuvants, Immunologic↗

Circulating antioxidants and lipid peroxidation products in untreated tuberculosis patients in Ethiopia.

BACKGROUND: Knowledge of the antioxidant profile and its relation to lipid peroxidation in tuberculosis patients with or without accompanying HIV infection is scarce, particularly in developing countries. OBJECTIVE: The objective was to further investigate the interaction between HIV, tuberculosis, and antioxidants and their relations with markers of oxidative stress in a large population of Ethiopians. DESIGN: In a cross-sectional study, we evaluated antioxidants and markers of oxidative stress in Ethiopian tuberculosis patients with (n = 25) and without (n = 100) HIV infection and in Ethiopian (n = 45) and Norwegian (n = 25) healthy control subjects. RESULTS: Concentrations of the antioxidant vitamins C and E and of vitamin A were significantly lower in tuberculosis patients than in healthy Ethiopians. Tuberculosis patients also had significantly lower thiol concentrations, particularly of the reduced forms. Tuberculosis patients, particularly those who were co-infected with HIV, had higher malondialdehyde concentrations than did control subjects. High malondialdehyde concentrations were associated with clinical severity as measured by the Karnofsky Performance Status Index and anthropometric scores. Ethiopian control subjects had lower concentrations of vitamin E and higher concentrations of malondialdehyde than did Norwegian control subjects. CONCLUSIONS: Our findings further support a link between oxidative stress, tuberculosis, and HIV infection. However, whether antioxidant supplementation will improve tuberculosis outcome or is of importance for its prevention should be further examined in future prospective studies.

Acquired Immunodeficiency Syndrome↗

Anaemia-related impairment in quality of life in elderly cancer patients prior to chemotherapy.

PURPOSE: Quality of life (QoL) of patients with cancer is a major area of concern for both patients and their physicians. PATIENTS AND METHODS: We investigated QoL with the EORTC-QLQ-C30 questionnaire with reference to anaemia and Karnofsky Performance Status (KPS) prior to the start of chemotherapy in 477 patients: 195 elderly cancer patients (Group A), 152 younger cancer patients (Group B), and 130 patients aged 60 years or older admitted for non-cancer related disorders (Group C). RESULTS: In univariate analysis QoL was significantly worse in 8 out of 15 scales in anaemic compared to non anaemic patients in Group A, in 2 in Group B, and in 7 in Group C. In ANOVA analysis including KPS and haemoglobin status, the influence of anaemia and KPS independently persists in most scales in Group A, in some in Group C, but not in Group B. CONCLUSIONS: Anaemia and functional impairment are independently related to QoL in elderly cancer and elderly medical patients, but not in younger cancer patients.

Age Factors↗

Limited-stage small-cell lung cancer: patient survival after combined chemotherapy and radiation therapy with and without treatment protocols.

PURPOSE: To compare survival of patients who undergo treatment in protocols versus survival of patients not in protocols. MATERIALS AND METHODS: Records of 81 adult patients with small-cell lung cancer who underwent chemotherapy and radiation therapy in 1987-1992 were reviewed retrospectively. Forty-one patients were in a protocol; 40 patients were not. Patient demographics and prognostic factors were not statistically significantly different. RESULTS: Median overall survival was 16.7 months in the nonprotocol group versus 29.0 months in the protocol group (P = .0023). Median disease-specific survival was 18.3 months in the nonprotocol group versus 27.1 months in the protocol group (P = .0176). Survival was not statistically significantly influenced by Karnofsky performance status, weight loss, or thoracic radiation dose. CONCLUSION: There was a highly statistically significant difference in survival outcome in the nonprotocol group versus the protocol group (P = .0023). Differences in chemotherapy-radiation therapy timing and other treatment-related factors may have contributed substantially to the improved survival in the protocol group.

Adult↗

Coping, distress, and survival among patients with lung cancer.

BACKGROUND: This study addresses the question of whether coping and emotional state are predictors of survival among patients with lung cancer. The hypotheses were (1) active coping is linked with longer survival time and (2) depressive coping, emotional distress, and depression are linked with shorter survival. METHODS: The study was based on a sample of 103 patients who were investigated after their diagnosis and before the beginning of primary treatment. The psychological variables were assessed by means of self-reports and interviewer ratings. After follow-up of 7 to 8 years, 92 patients had died; survival data were censored for the remaining 11 patients. The prediction of the survival time was performed by the Cox regression, while adjusting for biomedical risk factors (tumor stage, histological classification, and Karnofsky performance status). RESULTS: The self-reported depressive coping (P = .007) and the interviewer-rated emotional distress (P = .04) were significantly associated with shorter survival, independent of the influence of the biomedical prognostic factors. CONCLUSIONS: Both coping and emotional distress had a statistically independent effect on survival among patients with lung cancer. However, the naturalistic design of the study does not allow for any causal interpretation. Thus, the nature of this relationship warrants further investigation.

Adaptation, Psychological↗

Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis.

Survival for patients with glioblastoma multiforme is short, and current treatments provide limited benefit. Therefore, there is interest in conducting phase 2 trials of experimental treatments in newly diagnosed patients. However, this requires historical data with which to compare the experimental therapies. Knowledge of prognostic markers would also allow stratification into risk groups for phase 3 randomized trials. In this retrospective study of 832 glioblastoma multiforme patients enrolled into prospective clinical trials at the time of initial diagnosis, we evaluated several potential prognostic markers for survival to establish risk groups. Analyses were done using both Cox proportional hazards modeling and recursive partitioning analyses. Initially, patients from 8 clinical trials, 6 of which included adjuvant chemotherapy, were included. Subsequent analyses excluded trials with interstitial brachytherapy, and finally included only nonbrachytherapy trials with planned adjuvant chemotherapy. The initial analysis defined 4 risk groups. The 2 lower risk groups included patients under the age of 40, the lowest risk group being young patients with tumor in the frontal lobe only. An intermediate-risk group included patients with Karnofsky performance status (KPS) >70, subtotal or total resection, and age between 40 and 65. The highest risk group included all patients over 65 and patients between 40 and 65 with either KPS<80 or biopsy only. Subgroup analyses indicated that inclusion of adjuvant chemotherapy provides an increase in survival, although that improvement tends to be minimal for patients over age 65, for patients over age 40 with KPS less than 80, and for those treated with brachytherapy.

Adult↗

Hyperfractionated and accelerated-hyperfractionated radiotherapy for glioblastoma multiforme.

Because of promising radiobiological advantages allowing dose escalation and/or reduction of treatment time, hyperfractionated and accelerated-hyperfractionated radiotherapy (hf-rt, ahf-rt) were introduced as part of treatment of glioblastoma multiforme (gbm). In December 1988 we started a prospective study of hf-rt (total dose 78 Gy, two daily fractions of 1.3 Gy, interval between daily fractions 6 hr, treatment time 6 weeks, n = 34 patients). The results were compared with our previous regimen of conventionally fractionated radiotherapy (cf-rt: total dose 60 Gy, single dose 2 Gy, treatment time 6 weeks, n = 32 patients). In June 1990, the protocol was modified in order to reduce treatment time (ahf-rt: total dose 60 Gy, two daily fractions of 1.5 Gy, interval 6 hr, treatment time 4 weeks, n = 92 patients until December 1996). No chemotherapy was given. Entry criteria were: age > or = 17 years, pathological diagnosis of supratentorial gbm, and no previous treatment other than surgery. The ahf-rt group included significantly more patients with previous surgical resection instead of biopsy only. Compared with the cf-rt group, both the hf-rt and the ahf-rt group included significantly more patients with frontal tumor location. We found no significant survival difference between the groups (median survival 7-10 months, 1-year survival rate 19%-29%). Progression-free survival, clinical course, and toxicity were also not significantly different. Karnofsky performance status, age, and corticosteroid dose during radiotherapy were the most important prognostic factors. The results of this trial are in large agreement with most previous publications. It demonstrated no improved survival. However, it showed that treatment time can be reduced by ahf-rt without loss of survival benefit or intolerable toxicity. A short radiotherapy course might be appropriate for many patients with gbm who are not suitable for rather aggressive investigational therapies.

Adolescent↗

The benefits of surgery in the treatment of pelvic metastases.

This retrospective study analyses the benefit of surgery to patients with pelvic metastases. Forty-three patients were operated on between 1980 and 1992, 37 having intralesional and 6 extralesional resections. Thirty-nine had perioperative adjuvant therapy. Survival time was calculated by the Kaplan-Meier method. Clinical evaluation used the Karnofsky performance status which showed improvement from 55% before operation to 74% at 3 months (p = 0.0001) and 77% after 6 months (p = 0.0001). Those having an intralesional resection had a median survival time of 13 months, a complication rate of 24% and a local recurrence rate of 19%. The comparable figures for those with extralesional resection were 16 months survival, complications in 3 out of 6, and no local recurrences. The quality of life was improved by operation and intralesional resection is preferable in most of these patients.

Adult↗

Relapse of primary central nervous system lymphoma: clinical features, outcome and prognostic factors.

Data on relapsed primary central nervous system lymphoma (PCNSL) are limited. We have evaluated the clinical characteristics and outcome of relapsed PCNSL patients from two German trials. Patients with relapsed disease after primary treatment were studied. Primary therapy consisted of high-dose methotrexate-based chemotherapy in all patients. Treatment for relapse was not predetermined. After a median follow-up of 22.5 months, 52 (36%) patients with relapse were identified among 143 patients with complete remission (CR) after primary treatment. The median disease-free survival was 10.25 (3-47.5) months. The median age at relapse was 59 years. Forty-four of 51 evaluable patients relapsed within the CNS, 6 systemically and one both cerebrally and systemically. The median survival time after first relapse was 4.5 (0.5-40.5) months. Karnofsky performance status (KPS) at relapse (P = 0.004), site of relapse (isolated systemic versus other, P = 0.049) and treatment for relapse (versus no treatment, P = 0.001) were independent prognostic factors for survival after relapse in multivariate analysis. Survival of patients with relapsed PCNSL is poor despite high response rates to salvage therapy. Good KPS, isolated systemic relapse and treatment for relapse were significantly associated with longer survival.

Adult↗

A brief symptom index for advanced renal cell carcinoma.

BACKGROUND: Our objective was to test a brief, symptom index for advanced renal cell carcinoma, a disease affecting over 38,000 Americans each year and often diagnosed in late stages. METHODS: We conducted secondary data analyses on patient-reported outcomes of 209 metastatic renal cell carcinoma patients participating in a Phase III clinical trial. Patient-reported outcomes, obtained from the FACT-Biological Response Modifier (FACT-BRM) scale, were available at baseline, 2, and 8 weeks. We analyzed data from eight FACT-BRM items previously identified by clinical experts to represent the most important symptoms of advanced renal cell carcinoma. Items comprising this index assess nausea, pain, appetite, perceived sickness, fatigue and weakness, with higher scores indicating fewer symptoms. We determined reliability and validity of the index and estimated a minimally important difference. RESULTS: The index had excellent internal reliability at all three time points (alphas > or = 0.83). Baseline scores were able to discriminate patients across Karnofsky performance status, number of metastatic sites, and risk group categories (ps < .01). Mean index scores declined over time likely indicative of the toxic nature of the administered treatments. Distribution- and anchor-based methods converged on a minimally important difference estimate of 2 to 3 points. CONCLUSION: The 8-item index of patient-reported symptoms of renal cell carcinoma appears to be a psychometrically sound measure. It is a brief, reliable, and valid measure that can easily be adapted for use in clinical trials and observational studies.

Antineoplastic Agents↗

Phase II trial of imatinib (Gleevec) in patients with metastatic renal cell carcinoma.

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated on a Phase II trial with imatinib. Eligible patients had histologically confirmed RCC, metastatic and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), Karnofsky performance status (KPS) of at least 70%, life expectancy of more than 3 months, and adequate hematological, renal, and liver function. Imatinib was given orally at a dose of 400 mg bid. The most common toxicities were Grade II/III nausea (28%) and Grade II renal insufficiency (14%). All patients had tumor tested by immunohistochemistry (IHC) for KIT protein (CD117, DAKO). One tumor (7%) demonstrated strong, diffuse expression and the rest were negative. No complete or partial responses were observed in 12 evaluable patients treated with imatinib.

Aged↗

Impact of adding concurrent chemotherapy to hyperfractionated radiotherapy for locally advanced non-small cell lung cancer (NSCLC): comparison of RTOG 83-11 and RTOG 91-06.

A hyperfractionated radiation therapy (HFX RT) trial (1.2 Gy twice daily, b.i.d.) (HFX) for non-small cell lung cancer (NSCLC) showed that 69.6 Gy resulted in better survival than did lower total doses (Radiation Therapy Oncology Group, RTOG 83-11) and that cisplatin concurrent with irradiation improved local control and survival over RT alone (Radiation Therapy Oncology Group, RTOG 91-06). Concurrent combination chemotherapy and HFX could improve both local and systemic control. In a phase II trial (RTOG 91-06) for inoperable NSCLC, two cycles of PE were used [cisplatin 50 mg/m2 intravenously (i.v.) days 1 and 8, etoposide 50 mg orally (p.o.) b.i.d., 75 mg/day if body surface area (BSA) < 1.7 m2, days 1-14] starting on day 1 of HFX (69.6 Gy) and repeated on day 29. HFX/PE was compared with HFX (69.6 Gy) from an earlier phase II trial (RTOG 83-11). Seventy-six patients treated with HFX/PE and 203 patients who received HFX alone were compared for toxicity, response, survival, and patterns of failure. The rates of grade 4 nonhematologic toxicity were similar (3.0% for HFX/PE, 3.0% for HFX), but grade 4 hematologic toxicity occurred only with HFX/PE 56.6%. Three (3.9%) HFX/PE patients had fatal toxicity (2 pulmonary, 1 renal); 1 HFX patient had fatal esophageal toxicity. Response and metastasis rates were similar for the two treatments, but infield (p = 0.054) and overall (p = 0.04) progression-free survival rates were better with HFX/PE. Median survivals were 18.9 months with HFX/PE and 10.6 months with HFX. Two-year survival rates were 36% for HFX/PE and 22% for HFX (p = 0.014). The differences in survival between HFX/PE and HFX remained borderline statistically significant (p = 0.0593) in the multivariate model, which included weight loss, Karnofsky performance status (KPS), sex, and stage. HFX/PE is an effective regimen in patients with inoperable NSCLC, although it is considerably more toxic, and is undergoing a comparison in a three-arm randomized phase III study against induction cisplatin/vinblastine plus standard once-daily RT and against cisplatin/vinblastine concurrent with standard RT.

Administration, Oral↗

Quality of life for oncology patients during the terminal period. Validation of the HRCA-QL index.

AIM: The evolution of performance status, disability, and quality of life (QL) according to the Hebrew Rehabilitation Center for Aged QL (HRCA-QL) index for cancer patients through their terminal period is described. The assessment of HRCA-QL validity and reliability is also described. DESIGN: A total of 200 cancer patients were followed up from the onset of their "terminal phase" until they died. Information on symptoms, performance, disability and QL were collected by patient's oncologists in hospital and by their family practitioners and community nurses when the patient was at home. Health measures were: the HRCA-QL index, Karnofsky performance status (KPS) and the Independence in Activities of Daily Living (IADL) index. RESULTS: The three indices were acceptable for a fair number of patients at the start of the terminal phase. Almost two-thirds had a KPS > or =60. With respect to the IADL index, the patients were independent in five of the six functions, with 80% having a HRCA-QL equal to or greater than 4. The median duration of the terminal period was 59 days. All three indices declined progressively, with marked deterioration in the last 2 weeks. The HRCA-QL index was highly correlated with KPS and the IADL index, had good internal consistency and showed an acceptable test-retest and inter-rater reliability. The HRCA-QL index was reactive to clinical changes. CONCLUSIONS: All three scales confirmed that terminal patients experience a progressive loss of performance, increase in dependence and deterioration of QL as they approach the end of life. Based in these results, we consider the HTCA-QL index valid for use in terminal cancer patients.

Activities of Daily Living↗

Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study.

PURPOSE: To determine the benefit of whole brain radiotherapy (WBRT) and the use of the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system in patients with brain metastases from renal cell carcinoma. METHODS AND MATERIALS: We identified 46 consecutive patients with brain metastases from renal cell carcinoma who were treated with WBRT at the Cleveland Clinic Foundation between 1983 and 2000. We reviewed their charts for patient and tumor characteristics and categorized them according to the RTOG RPA classes. RESULTS: The median follow-up and survival time for all 46 patients (15 women and 31 men) was 3.0 months. The median radiation dose was 3000 cGy in 10 fractions. Patients who received higher radiation doses (>3000 cGy) survived longer than those who received 3000 cGy or less than 3000 cGy (8.5 months vs. 2.7 months vs. 0.4 months, p = 0.0289). However, the Karnofsky performance status and RPA class were confounding factors in these data. The median survival for patients by RTOG RPA class was 8.5 months for Class I (n = 2), 3 months for Class II (n = 37), and 0.6 months for Class III (n = 7, p = 0.0834). CONCLUSION: Despite the relatively poor prognosis of patients who receive WBRT alone, it appears that they benefit from this palliative treatment. The RTOG RPA classification system may be a useful tool in assessing prognosis in this patient population.

Adult↗

Phase II trial of arsenic trioxide in patients with metastatic renal cell carcinoma.

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated on a Phase II trial with arsenic trioxide (As2O3). Eligible patients had metastatic renal cell carcinoma with bidimensionally measurable disease, a Karnofsky performance status of at least 70%, life expectancy of greater than three months, and no evidence of brain metastases. Arsenic trioxide was given intravenously at a dose of 0.3 mg/kg/day for five consecutive days every four weeks. The most common toxicity observed was grade II elevation in liver function tests (36%), anemia (21%), renal insufficiency (14%), rash (7%), and diarrhea (7%). Best response was stable disease in 3 patients with one patient remaining on study at 8+ months At the dose and schedule used in this trial, arsenic trioxide did not achieve a complete or partial response in metastatic renal cell carcinoma.

Adult↗