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Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial.

PURPOSE: Chemotherapy with alkylating agents is of proven efficacy in recurrent anaplastic oligodendroglioma (AO) with reported response rates ranging between 50% and 70%. The response of newly diagnosed AO to initial treatment with temozolomide (TMZ) has not yet been reported. This study evaluated the response and time to tumor progression of newly diagnosed AO initially treated with TMZ. PATIENTS AND METHODS: Twenty patients with a median age of 47 (range: 26-65) received a median of 14 (range: 3-24) cycles of TMZ as their first modality of therapy following diagnosis of AO. Treatment was given every 28 days for 5 days at a starting dose of 200 mg/m2/d and was continued for 24 cycles unless toxicity or tumor progression required withdrawal of TMZ. MRI evaluations were repeated every 8 weeks and scales of Karnofsky performance status (KPS) and of neurological function were used to assess clinical response. RESULTS: Clinical improvement was observed in 60% of the patients with statistically significant gain measured by KPS and the neurologic function scales. The objective response rate was 75%, and median time to tumor progression was 24 months. Maximal objective response was reached within a median of 6 months (range: 3-12). Tumors with 1p loss had longer progression free survival compared to tumors without deletions (PFS at 24 months: 1p LOH = 100%, 1p intact = 20%; P = 0.057). TMZ was well tolerated with only two events of grade 3/4 hematological toxicity. CONCLUSIONS: Newly diagnosed AO demonstrates a high rate of response to initial therapy with TMZ, similar to the response reported for PCV combination therapy. Further studies are needed to determine the optimal duration of treatment and whether radiotherapy should immediately follow chemotherapy.

Adult↗

A North American brain tumor consortium (NABTC 99-04) phase II trial of temozolomide plus thalidomide for recurrent glioblastoma multiforme.

BACKGROUND: Laboratory and clinical data suggest that the anti-angiogenic agent, thalidomide, if combined with cytotoxic agents, may be effective against recurrent glioblastoma multiforme (GBM). OBJECTIVES: To determine 6-month progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in adults with recurrent GBM. PATIENTS AND METHODS: Eligible patients had recurrent GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was given at 150-200 mg/m(2)/day on days 1-5 of each 28-day cycle. Thalidomide was given orally at 400 mg at bedtime (days 1-28) and increased to 1,200 mg as tolerated. Patients were evaluated with magnetic resonance imaging scans every 56 days. The study was designed to detect an increase of the historical 6PFS for GBM from 10 to 30%. RESULTS: Forty-four patients were enrolled, 43 were evaluable for efficacy and safety. The study population included 15 women, 29 men; median age was 53 years (range 32-84); median Karnofsky performance status was 80% (range 60-100%). Thirty-six (82%) patients were chemotherapy-naïve. There were 57 reports of toxicity of grade 3 or greater. Non-fatal grade 3-4 granulocytopenia occurred in 15 patients (34%). The objective response rate was 7%. The estimated probability of being progression-free at 6 months with this therapy is 24% [95% confidence interval (C.I.) 12-38%]. The median time to progression is 15 weeks (95% C.I. 10-20 weeks). There was no observed correlation between serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and the 6PFS outcome. CONCLUSION: This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone.

Adult↗

Low-grade gliomas.

Low-grade gliomas are uncommon primary brain tumors classified as histologic grades I or II in the World Health Organization (WHO) classification. The most common variants are pilocytic and low-grade astrocytomas, oligodendrogliomas, and mixed oligo-astrocytomas located in the cerebral hemispheres. Prognostic factors that predict progression-free and overall survival include young age, pilocytic histology, good Karnofsky performance status, gross total resection, lack of enhancement on imaging, and small preoperative tumor volumes. Edema and vasogenic effects are typically managed with corticosteroids. Dexamethasone is given at an initial dosage of 4 mg given four times daily. Anticonvulsants are given prophylactically after resection and for patients who present with seizures. The rationale for open craniotomy depends on the need for immediate palliation of symptoms by reduction of intracranial pressure or focal mass effect, and/or improved oncologic control. Gross total resection of tumor is generally defined as the absence of residual enhancement on contrast-enhanced postoperative MRI scan. Most retrospective studies suggest that patients who have undergone a gross total resection of tumor have improved survival. Depending upon the proximity of the tumor to eloquent brain, gross total resection may or may not be possible. In these cases a stereotactic biopsy is required to provide the histologic diagnosis. Adjuvant radiotherapy is recommended for patients with incompletely resected grade II tumors or for patients older than age 40 regardless of extent of resection. It may be considered for any pilocytic astrocytoma from which a biopsy has been performed. Phase III randomized prospective trials have shown statistically significantly improved progression-free survival at 5 years with the addition of radiotherapy, though overall survival does not appear different. Based on prospective randomized phase III trials, 50.4 Gy to 54 Gy of conventionally fractionated radiotherapy appears to be a safe and effective regimen with minimal neurotoxicity; 45 Gy may be adequate for biopsied pilocytic astrocytomas. Currently, RTOG trial 98-02 is investigating the efficacy of postradiation PCV chemotherapy (procarbazine, CCNU, and vincristine) in the treatment of newly diagnosed unfavorable low-grade gliomas. Other areas of investigation include Temozolomide chemotherapy and the association of 1p and 19q chromosomal deletions with prolonged survival in oligodendrogliomas and sensitivity to PCV chemotherapy. Radiosurgery and/or experimental chemotherapy may provide some measure of local control in the recurrent disease setting.

Adolescent↗

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.

PURPOSE: To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS). PATIENTS AND METHODS: Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing. RESULTS: Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens. CONCLUSIONS: In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder.

Adolescent↗

Photodynamic therapy for obstructing esophageal cancer: light dosimetry and randomized comparison with Nd:YAG laser therapy.

BACKGROUND & AIMS: Light dosimetry analysis to achieve predictable tumor necrosis has not been performed for photodynamic therapy (PDT) in the gastrointestinal tract. We evaluated dihematoporphyrin ethers for sensitizing esophageal carcinomas to 630 nm light and compared PDT with neodymium:yttrium-aluminum-garnet (Nd:YAG) laser therapy in a randomized trial. METHODS: Of 52 patients with dysphagia, 32 received palliative PDT. Ten patients treated with PDT participated in a preliminary trial using various doses of 630-nm light, and 22 patients treated with PDT participated in a randomized trial using a derived standardized light dose for comparison with 20 patients treated with the Nd:YAG laser. RESULTS: Light dosimetry correlated with depth of tumor necrosis (r = 0.664; P < 0.001). PDT activity was similar for squamous cell and adenocarcinoma. Among randomized patients, both PDT and Nd:YAG therapy relieved dysphagia, but PDT resulted in improved Karnofsky performance status at 1 month (+7 vs. -7; P < 0.001) and longer duration of response (84 vs. 57 days; P = 0.008). Skin photoreactions were unique to PDT. CONCLUSIONS: The extent of PDT tumor ablation correlates with light dosimetry, enabling selection of a standardized light dose. PDT can relieve esophageal obstruction from squamous cell and adenocarcinoma and is an alternative to Nd:YAG thermal necrosis with a longer duration of response. However, PDT requires patient precautions to minimize skin photoreactions.

Adenocarcinoma↗

The efficacy of cranial irradiation in ovarian cancer metastatic to the brain: analysis of 32 cases.

OBJECTIVE: To determine the role of irradiation in the management of brain metastases from epithelial ovarian cancer. METHODS: Tumor registries from five university cancer centers were searched to identify ovarian cancer patients with brain metastases. During a 30-year period (1965-1994), 4027 ovarian cancer patients were evaluated, 32 of whom were found to have cerebral metastases. Each received fractionated whole-brain irradiation (median dose 30 Gy, range 20-52.5). Five patients received concomitant chemotherapy with whole-brain irradiation. RESULTS: The median survival time for the whole population was 4 months. For the entire series, symptomatic response (complete response and partial response) was achieved in 23, 16 of whom were palliated until death. Patients with higher Karnofsky performance status (70 or above versus below 70) were more likely to derive a palliative response and attained a statistically significant survival advantage. No other factor predicted the likelihood of deriving a palliative response or a survival advantage after treatment. CONCLUSIONS: In this large review of patients with cerebral metastases from ovarian cancer, we found that most of those treated with whole-brain irradiation achieved palliation until death. Nearly all women with high performance status derived durable palliation from cerebral irradiation. Whole-brain irradiation was an effective means of palliating ovarian cancer metastatic to the brain and provided a favorable alternative to other means of management.

Adult↗

Prognostic factors in low-grade supratentorial astrocytomas: a uni-multivariate statistical analysis in 76 surgically treated adult patients.

A retrospective uni-multivariate statistical analysis was performed on 32 prognostic factors to investigate their importance in predicting survival in a series of 76 adult patients with low-grade supratentorial astrocytomas treated over a 13-year period. The end point used for this study was the length of survival. The median survival time was 40 months. Overall actuarial survival at 2, 5, and 10 years was 69%, 38%, and 22%, respectively. Radical resection of the neoformation, a higher preoperative Karnofsky performance status (KPS) score, and an age younger than 50 years are strongly correlated with survival; postoperative radiotherapy appears to be associated with increased survival only in patients under 50 years of age.

Actuarial Analysis↗

Esophageal cancer.

Esophageal cancer is an important problem in the United States. It results in more deaths (over 10,000 annually) than rectal cancer. Furthermore, the incidence of esophageal adenocarcinoma is increasing at a rate faster than that of nearly any other cancer and the reasons for the increase are not well understood. A variety of tumor-suppressor genes (including p53, APC, DCC and Rb) and proto-oncogenes (including prad1, EGFR, c-erb-2 and TGF alpha) may be involved in the development and progression of esophageal cancer. Clinical prognostic factors include stage, Karnofsky performance status, sex, age, anatomic location of the tumor, and degree of weight loss. A new staging system based on depth of wall penetration and lymph node involvement correlates well with prognosis for patients undergoing esophagectomy. Newer staging procedures including endoscopic ultrasound as well as the use of minimally invasive surgery, such as thoracoscopy and laparoscopy, may allow accurate staging without esophagectomy. Surgical resection provides excellent palliation; however, the chance for cure with esophagectomy alone is only 10% to 20%. Adjuvant treatment with pre- or postesophagectomy radiation may improve local-regional control but does not improve survival. Nor has preoperative chemotherapy been shown to improve survival; however, it remains an active area of investigation. Multimodality therapy, namely, chemotherapy and radiation (chemoradiation), given concurrently prior to surgical resection shows promise, with one study indicating a 5-year survival of 34%. A complete pathologic response to chemoradiation correlates with improved survival. Chemoradiation has been shown to be superior to radiation as primary management of esophageal cancer. There has been no successfully completed randomized trial of surgery versus definitive radiation or chemoradiation. However, chemoradiation represents a reasonable alternative to esophagectomy in the primary management of squamous cell carcinoma of the esophagus and chemoradiation also appears to be effective in the treatment of patients with adenocarcinoma of the esophagus, offering significant palliation and a chance for long-term survival as well. Randomized studies of preoperative chemoradiation versus surgery or versus chemoradiation alone are needed. The treatment of advanced esophageal cancer must be directed toward palliation of symptoms. Newer endoscopic techniques, including the use of expansile metal stents, laser ablation, intraluminal high-dose rate brachytherapy, BICAP tumor probe, or photodynamic therapy, offer selected patients short-term palliation.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Depression and abnormal illness behavior in cancer patients.

Evaluation of the incidence of depression among cancer patients has been the object of a number of studies. Recent reports of medically ill patients have indicated that depression is related to several dimensions of abnormal illness behavior (e.g., hypochondriasis, irritability, denial, disease conviction). To investigate the relationship between depression and abnormal illness behavior in cancer patients, a study was conducted of 196 patients with a recent diagnosis of cancer and with a good performance status (Karnofsky score greater than 80). The Hamilton Depression Rating Scale (HDRS) and the Illness Behavior Questionnaire (IBQ) were administered in their validated Italian forms. A cutoff point of 17 on the HDRS revealed 38.26% of the patients as having symptoms of depression, whereas a more conservative cutoff point of 21 indicated a depressive state in 23.97% of the patients. Depressed patients had higher scores on all the IBQ dimensions except that of psychologic versus somatic perception of illness. The results were confirmed by the correlation between the parameters. Higher levels of denial were reported by females and by patients receiving adjuvant or palliative chemotherapy, who had, however, lower levels of dysphoria than patients not receiving treatment. Higher levels of irritability were shown in hospitalized patients. No relationship was found between medical status variables (Karnofsky score, tumor status, and disease extent) and psychologic measures, except for denial. The findings seem to confirm the importance of assessment of depression and illness behavior in cancer patients and suggest the need for more thorough investigation of the psychosocial variables associated with them.

Adult↗

Intraoperative plus external beam irradiation in nonresectable lung cancer: assessment of local response and therapy-related side effects.

Since 1987, 24 patients with inoperable non-small-cell lung cancer (NSCLC), stage T1-3 N0-2 M0, have undergone lymph node dissection and intraoperative radiation therapy (IORT) to the primary with 10-20 Gy. Patient selection criteria were nonresectability based on severe cardiorespiratory impairment, no radiological evidence of distant metastases and a Karnofsky performance status of greater than 80. In 18 patients the IORT procedure was followed by an external beam radiation series (EBR) including the tumor with 46 Gy and the regional lymph nodes with 46/56 Gy. The tumor response was assessed by CAT-scan volumetry before the institution of IORT, 4 weeks later, before the onset of EBR, 8 weeks after the combined treatment course and on a 3 months basis thereafter. Prospectively, MRI of the thorax with/without Gadolinium-DTPA was performed to examine contrast enhancement and signal behavior of the tumor, in an attempt to differentiate residual disease compared to therapy-related collateral damage. So far, 18 patients have completed the combined treatment course with a median follow-up of 11 months (range 4.5 to 25 months). The overall local response rate (CR and PR) was 88.2%. In detail, 11 complete responses, 6 partial responses and one minimal response were observed. The overall and recurrence-free survival at 25 months was 49.6% and 83.3%, respectively.

Aged↗

Analysis of early and late deaths on RTOG non-small cell carcinoma of the lung trials: comparison with CALGB 8433.

UNLABELLED: In a major study that showed a treatment advantage for induction chemotherapy followed by radiation therapy (CALGB 8433), there was a significantly (P = 0.02) lower proportion of patients dying within 105 days of registration in the chemotherapy/radiation arm than the radiation therapy arm; without this difference, the overall survival was marginally better (P = 0.059) for the chemotherapy/radiation group. A retrospective analysis of RTOG trials sought explanations for the phenomenon. MATERIALS AND METHODS: Patients who fit the CALGB eligibility criteria and received radiation therapy alone in four prospective trials of the RTOG conducted between 1983 and 1989 were analyzed to determine factors that distinguished patients dying within 105 days from longer survivors. Two were trials of altered fractionation and two used standard fractionation. Of 683 patients identified, 107 (15.7%) died within 105 days after registration. The log linear model was used to evaluate relationships between death within 105 days and known prognostic factors. Karnofsky performance status (KPS), < 90 vs. > or = 90, was the only factor significantly related to death within 105 days (P = 0.0052). A Cox model with the same factors plus fractionation and total dose found KPS and T-stage associated with overall survival (P = 0.0005 and 0.025, respectively). The choice of the hyperfractionation arm (HFX) for Phase III study (69.6 Gy at 1.2 Gy b.i.d.) was based in part on comparison with standard fractionation (STD) from a concurrent RTOG protocol, 8321. Review of early deaths showed that this HFX arm had a lower proportion of patients dying within 105 days (7.9%) than STD in 8321 (21.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and other prognostic indicators in squamous cell lung cancer.

Multivariate models of survival have been established for both small cell and non-small cell lung cancers. So far, no study has focussed on squamous cell types. Previous demonstrations of the prognostic value of the tissue polypeptide antigen (TPA) and, partially, of the carcinoembryonic antigen (CEA) are based on univariate analyses of survival. These analyses do not account for the other prognostic factors. In the present study, we report the combined influence of various clinical and biological characteristics on the survival duration of 360 patients with a newly diagnosed squamous cell carcinoma of the lung. The study comprised 29 variables, including age, sex, smoking habit (SH), symptoms at diagnosis, the Karnofsky performance status (KPS), weight loss (WL), radiological findings, various disease extent parameters (DEP), CEA and TPA. Preliminary univariate analyses showed that 20 variables were survival-related. The Cox proportional hazards regression analysis selected stage of disease, KPS, TPA, WL, the existence of bone metastases, and SH as independent factors of prognosis (global chi-square: 122.40, P = 0.0000). A second multivariate analysis, performed with the same covariates but excluding DEP, revealed previous pulmonary diseases and CEA to be, in addition to KPS, TPA, SH, and WL the next most influential prognostic determinants. Also in squamous cell lung cancer, classifications based on the Cox's prediction equation may improve individual counseling and patient selection for therapeutic trials. In this malignancy, TPA shows an independent and strong prognostic significance while CEA shares informations of diverse other prognostic factors and seems to be less important.

Adult↗

Pre-treatment prognostic factors in patients with stage III non-small cell lung cancer treated with hyperfractionated radiation therapy with or without concurrent chemotherapy.

We analyzed prognostic factors for non-small cell lung cancer (NSCLC) treated with hyperfractionated radiotherapy (HFX RT) with or without concurrent chemotherapy. One-hundred sixty-nine patients with histologically or cytologically proven, Stage III NSCLC, Karnofsky performance status (KPS) > or = 50, and no previous therapy were treated in a randomized trial as follows: Group 1--HFX RT to a total dose of 64.8 Gy (61 patients); Group 2--the same HFX RT with chemotherapy consisting of 100 mg of carboplatin on days 1 and 2 and 100 mg of etoposide on days 1-3 of each week during the RT course (52 patients); and Group 3--the same HFX RT with chemotherapy consisting of 200 mg of carboplatin on days 1 and 2 and 100 mg of etoposide on days 1-5 of the first, third, and fifth weeks of the RT course (56 patients). The median survival time for all 169 patients was 13 months and the 5-year survival rate was 13.4%. The median time to relapse (local or distant) was 11 months and the 5-year relapse-free survival was 12.8%. Group 2 patients had a better prognosis than Group 1 patients (P = 0.0028) but there were no differences in prognosis between Groups 2 and 3 and between Groups 1 and 3. Of potential prognostic factors examined, female gender (P = 0.00012), age > or = 60 (P = 0.00000), KPS > or = 80 (P = 0.00000), Stage IIIA (P = 0.00000), and previous weight loss < or = 5% (P = 0.00000) were associated with better prognosis. These findings were confirmed by multivariate analysis.

Adult↗

N-(phosphonacetyl)-L-aspartate (PALA) in advanced soft tissue sarcoma: a phase II trial of the EORTC soft tissue sarcoma group.

Thirty-six patients with measurable or evaluable advanced soft tissue sarcoma were entered in a phase II trial with PALA. Among the 27 evaluable patients, 15 were men, the median age was 55 yr (16-69) and the median performance status (Karnofsky) was 80 (50-100). Most patients had leiomyosarcoma (8), liposarcoma (3), neurofibrosarcoma (3), synovial cell sarcoma (3), or undifferentiated sarcoma (3). Indicator lesions consisted essentially of lung metastases (21) and/or soft tissue lesions (14). All patients had received prior chemotherapy with 1-5 regimens and 6 had achieved objective response with these previous treatments. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-17) were administered. Partial remission (greater than 50%) was obtained in one patient with a liposarcoma who had also responded to prior combination chemotherapy. This single response to PALA lasted 6 weeks from initiation of therapy. Four patients had unchanged disease after 6+ courses of PALA and 22 had progressive disease. Toxic effects were generally mild to moderate and included cutaneous toxicity (17), diarrhea (14), stomatitis (13), ocular manifestations, consisting of conjunctivitis, corneal ulceration and/or photophobia (11), nausea and vomiting (6) and, possibly, seizures (2). There was no evidence of drug-related myelosuppression. It is concluded that PALA given at the dose schedule selected for this trial has no significant antitumor activity in advanced soft tissue sarcoma previously treated with chemotherapy.

Adolescent↗

N-(phosphonacetyl)-L-aspartate (PALA) in advanced malignant melanoma: a phase II trial of the EORTC Malignant Melanoma Cooperative Group.

Thirty-nine patients with measurable advanced malignant melanoma were entered in a phase II trial with PALA. Among the 36 evaluable patients there were 18 men and 18 women, with a median age of 53 yr (29-73) and a median performance status (Karnofsky) of 100 (50-100). Indicator lesion consisted essentially of soft tissue lesions (29 patients) and/or lung metastases (9 patients). Only three patients had received prior chemotherapy. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-8) were administered. Partial response (greater than 50%) was obtained in 4 patients for 6-17 weeks. Eight patients had stable disease after 3 courses of PALA and 24 had progressive disease. Toxic effects were generally mild to moderate and mainly included cutaneous toxicity, nausea and vomiting, stomatitis, and diarrhea. Myelosuppression was rare and negligible. It is concluded that PALA given at the dose schedule selected for this trial is fairly well tolerated and has borderline antitumor activity in good-risk patients with advanced malignant melanoma.

Adult↗

Clinical improvement in advanced cancer disease after treatment combining histamine and H2-antihistaminics (ranitidine or cimetidine).

In a randomized study 31 patients with advanced cancer disease in whom classical anticancer therapy had been abandoned received a daily combination of subcutaneous histamine and oral H2-antihistaminics. In 27 patients, treatment induced a marked clinical improvement as shown by a large rise in performance status (Karnofsky scale). Ten patients were still alive 3-14 months after initiation of treatment. Average survival in the 31 treated patients (172 +/- 113 days) was significantly longer than in 34 non-treated patients with similar advanced cancer (26 +/- 16 days, P less than 0.00001). In six treated patients, the size of liver and lung metastases decreased. Histamine was perfectly tolerated up to 4 mg/day.

Adult↗

Quality of life during cytostatic therapy for advanced symptomatic colorectal carcinoma: a randomized comparison of two regimens.

Physician- and patient-rated 'quality of life' was studied in patients receiving chemotherapy for advanced symptomatic colorectal cancer. The patients participated in a Nordic multicentre randomized study comparing single-drug 5-fluorouracil (5-FU) with a combination of sequential methotrexate-5-FU with leucovorin rescue (MFL). Forty-four patients (all patients included at one of the hospitals) entered this associated 'quality of life' study, 22 in each group. In the MFL group, five patients had a partial remission (PR) and seven prolonged stationary disease (SD), whereas in the 5-FU group, only one patient had a PR and two SD. Median survival was longer in the MFL group (9 months) than in the 5-FU group (4 months). According to the physicians' judgement, 12 (55%) of the patients randomized to MFL experienced improved 'quality of life' compared to five (23%) in the 5-FU group. Patients' ratings gave the same figure (55%) in the MFL group, whereas only two (9%) patients in the 5-FU group considered themselves improved. The correlations between physicians' and patients' ratings were good. Adverse effects of treatment were minor and influenced ratings negatively only in one patient (5-FU group). Items that reflected changes in everyday activities discriminated better than other items in the 'quality of life' assessment. Since 'quality of life' measures were better in the MFL group in this associated study, and since objective and subjective responses, changes in Karnofsky performance status (KPS) and in survival also were better in the MFL group, not only in this study but also in the Nordic trial (249 patients randomized), we conclude that MFL is superior to 5-FU as a palliative treatment.

Adult↗

Interferon-related mental deterioration and behavioral changes in patients with renal cell carcinoma.

Five out of 38 patients (13%) with metastatic renal cell carcinoma had mental deterioration 3 weeks to 13 months after the start of treatment with recombinant interferon alpha-C. Metastatic spread to the brain, paraneoplastic effect of the tumor on the central nervous system and other causes of dementia were excluded. Computed tomography of the brain in these patients was normal and the width of the cerebral sulci and ventricles did not correlate with the severity of dementia. Specific patterns of atrophy were not seen. General deterioration, assessed by the change in Karnofsky performance status, was associated with dementia. The dementia may have been caused by a neurotoxic effect of interferon.

Aged↗