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PubMed2005

Intraocular lymphoma 2000-2005: results of a retrospective multicentre trial.

BACKGROUND: The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has yet to be defined. This study assesses the clinical characteristics and outcome of patients with IOL diagnosed and treated in the new millennium. METHODS: Patient data in this retrospective multicentre study were compiled by standardised questionnaires sent to seven university ophthalmology departments. All cases diagnosed with primary and secondary IOL in the past 5 years not associated with HIV infection were included. RESULTS: Twenty-two patients, 11 men and women; median age 64 (range 38-83) years, median Karnofsky performance status 90% (range 50-100%), were included. Nineteen patients had primary IOL (PIOL): 13 a newly diagnosed disease and six an ocular relapse of primary central nervous system lymphoma (PCNSL). Three patients had secondary IOL. First-line treatment for IOL included systemic chemotherapy in 13 cases, ocular radiation in six and intraocular chemotherapy in three. Complete remission was achieved in 14/20 evaluable patients, partial remission in five and stable disease in one. All patients treated with ifosfamide (IFO) or trofosfamide (TRO) (n=8) responded. Median progression-free survival (PFS) and overall survival were 10 (range 1+ to 44.5+) and 22.5 (range 1+ to 49+) months, respectively. Patients with newly diagnosed PIOL and ocular relapse of PCNSL had a median PFS of 10 (range 1+ to 44.5+) and 6 (range 2 to 6+) months, respectively. Median PFS was 12 (range 3+ to 22.5+) months after systemic and 5.5 (range 1+ to 44.5+) months after local first-line therapy. CONCLUSIONS: The prognosis of PIOL is similar to that of PCNSL without ocular involvement. Systemic therapy possibly prolongs PFS as compared with local management of (P)IOL. The high response rate to monotherapy with IFO and TRO is promising.

Adult↗
PubMed2002

Antibiotic prescription for fever episodes in hospice patients.

Bacterial infection usually plays an important part in the fever episodes that are common in patients in the hospice palliative care unit. The physicians' attitude to use of antibiotics in such cases is usually complex. We retrospectively studied 535 admissions to a hospice and palliative care unit in a medical center in Taiwan. Ninety-three fever episodes (16.7%) were identified among these admissions, and 79 fever episodes (84.9%) were treated with antibiotics. The Karnofsky performance status (KPS), verbal communication ability (VCA) and Glasgow Coma Scale (GCS) were all significantly compromised in these febrile patients. Although KPS, VCA and GCS were similar among all patients at the date of admission, these parameters became significantly worse in fever episodes that were left untreated than in those treated with antibiotics. Patients without antibiotic treatment showed a shorter mean survival (8.7 +/- 9.9 days vs 14.6 +/- 13.1 days; P = 0.03) and a higher 3-day mortality rate than those patients with antibiotic treatment (50% vs 15.2%; P = 0.015). In conclusion, appropriate antibiotic use may cause fever to subside and thus decrease the fever-related discomfort. Physicians may tend to withhold antibiotic treatment because of the poorer KPS, VCA, and GCS and poorer estimated prognosis of patients at the time of fever.

Aged↗
PubMed2003

Setting up a palliative care clinic within a radiotherapy department: a model for developing countries.

Nearly 50% of all newly diagnosed cancer patients in India (and other developing countries) are terminally ill with advanced disease. These patients are usually neglected or often receive futile anticancer treatment(s), whereas what they really need is maximum medical management in the form of palliative care and psychosocial support. Since advanced and incurable cancer cases are mostly referred for radiotherapy (RT), a palliative care (PC) clinic was started in the Department of Radiotherapy, PGIMER, Chandigarh. The PC clinic staff consisted of one specialist doctor, a nurse and volunteers. Previous disease and treatment records maintained by the RT colleagues were noted. Proforma-based assessments were done in the PC clinic and focused on patients' Karnofsky Performance Status, physical symptoms, drugs prescribed, and the doctor's or patient's/relative's response to/satisfaction with the treatment in each case. Prospective data on 100 patients (March to August 2001) revealed that various distressing physical symptoms (cachexia, dyspnoea, constipation) had not been routinely assessed earlier. Despite previous treatment, adequate pain management as per the WHO ladder was needed in 67 of 88 (76%) patients when they were seen by the PC team. On the regular follow-up visits to the PC clinic, 42% and 50% of the patients/relatives reported a response to and satisfaction with the treatment at their second and third visits. We believe two conclusions are justified. (1) Attention to palliative care needs could result in good treatment outcome and high level of patients' and doctors' satisfaction. (2) Since a specialist PC set-up is lacking in most medical institutions in India, the RT department is the best suited to delivery of palliative care for patients with advanced cancer.

Developing Countries↗
PubMed2004

Quality of life as a clinical trial endpoint: determining the appropriate interval for repeated assessments in patients with advanced lung cancer.

One of the unresolved design issues for clinical trials with quality of life (QOL) as an endpoint is the frequency of measurement in patients with stage III and IV lung cancer. In a retrospective review of clinical trials, the QOL interval varied widely from 1 to 12 weeks during treatment. During follow-up, the interval was generally 2 to 3 months or not at all. The purpose of this methodological study was to determine an appropriate interval for QOL serial measurement based on prospectively collected data. The 20 patients for this study were part of a phase I/I study using combination chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). They were typical of patients in lung cancer clinical trials, with a median age of 67 (interquartile range: 58, 72) years, the majority were male (13, 65%), and a baseline median Karnofsky performance status was 80 (interquartile range: 70%, 90%). The primary instrument, developed in 1985, was the Lung Cancer Symptom Scale (LCSS) patient form, a 9-item self-report and site-specific QOL measure. The method, outcome, and implication of these findings to research are presented for establishing a method for obtaining an appropriate serial measurement interval for QOL during therapy in clinical trials. Based on the findings of this study, an every 3-week QOL assessment for patients with advanced NSCLC provides data similar to more frequent evaluation (94% of data preserved compared to twice-weekly assessment, 95% confidence interval, 86-98%, p=0.05). Less frequent assessment (every 4 or every 6 weeks) retained less than 85% of the data, which is the recommended minimum adequacy rate. Retaining a high percentage of QOL information may lessen the effect of measurement bias due to patient attrition and may give more validity to QOL studies.

Adult↗
PubMed1997

Evaluation of the cost of home care for terminally ill cancer patients.

The aim of this work was to carry out a cost evaluation of the home care programme for terminally ill cancer patients run by the Istituto Oncologico Romagnolo (I.O.R.) in the areas of Forlì, Cesena, Ravenna and Rimini (Romagna, Italy). To determine effective home care direct costs, we first selected 1 week of care as an observation unit. We then proceeded to assess the medical and nursing care units together with the clinical protocols administered for each patient. The Karnofsky Performance Status (KPS) was also assessed weekly. In this way, we calculated care costs for each patient and for each week as the sum of medical costs, nursing costs, treatment costs and other costs. A consecutive series of 574 patients were involved in the study from 1 April 1994 to 31 March 1995. A total of 5164 patient-weeks of care was provided, with an average cost per week of 177.6 Ecu. This weekly cost increased in the last 100 days of life (week -15 = 179.5 Ecu; week -8 = 188.3 Ecu; week -2 = 221.0 Ecu; P < 0.001). When single components were analysed in relation to total cost (treatment protocols, physician and nursing care) the increased global cost was found to be mainly attributable to the intensification in nursing care (21.8% of costs in week -15 vs 27.3% of costs in week -2). Examination of the relation between the cost of 1 week of care and KPS values clearly shows that healthcare costs increased as KPS decreased (from 152.2 Ecu with KPS > or = 60 to 292.6 Ecu with KPS < or = 20; P < 0.001). Home care costs were also seen to vary with some clinical characteristics and symptoms present when patients entered the study: asthenia, anorexia, nausea/vomiting, bedsores. Given the good results of home care for cancer patients in terms of quality of life, this method of cost accounting for home-care providers can help to monitor the rising cost of assistance and confirm the cost effectiveness of this type of care.

Adolescent↗
PubMed1999

Normative data and trends in quality of life from the Lung Cancer Symptom Scale (LCSS).

Normative data and trends for a disease- and site-specific quality of life (QL) instrument for individuals with lung cancer, the Lung Cancer Symptom Scale (LCSS), are presented to facilitate the user's interpretation of test scores. Data for patients enrolled in two large, identical, randomized trials of a new combination chemotherapy regimen for patients with stages III and IV non-small-cell lung cancer (NSCLC) were combined into one dataset (n = 673). For these patients with a Karnofsky performance status (KPS) of 60-100%, QL had been prospectively measured at baseline, day 29 and every 6 weeks thereafter. Descriptive statistics for the LCSS are presented for three time points (baseline, day 29 and day 71) and for specific demographic and disease-related characteristics (age, gender, race, performance status and stage of disease) to provide expected values and their variability during chemotherapy. Data from a small dataset of 63 NSCLC inpatients with KPS scores of 20-50% are also presented for a comparison sample of supportive care for inpatients and hospice patients. For the 673 NSCLC patients at baseline there were no significant differences in QL by age, gender, or race. Major presenting lung cancer symptoms at baseline for this combined sample were dyspnea 87%, cough 86%, pain 81%, loss of appetite 75%, and hemoptysis 41%. Of these patients, 81% had three or more presenting symptoms at baseline (2% had no symptoms; 5%, one symptom; 12%, two symptoms; 18%, three symptoms; 27%, four symptoms; and 36%, five symptoms). The mean LCSS baseline score (best = 0; worst = 100) was 26.56 (SD 16.10). The mean scores for day 29 and day 71 were 25.46 (SD 16.52) and 25.30 (SD 16.93), respectively, but follow-up assessments on progressers were not obtained. Stage III patients had a mean LCSS score of 23.7 (SD 15.1), whereas stage IV patients reported a mean LCSS score of 27.3 (SD 16.3). The mean LCSS score for the group with KPS 60-70% was 34.8 (SD 15.5), and that for the group with KPS 80-100% was 23.3 (SD 15.1). The mean LCSS score for the lower performance group, with KPS scores of 20-50% at baseline, was 46.85 (SD 17.65).

Adult↗
PubMed2006

Clinical and endoscopic features of acute hemorrhagic rectal ulcer.

BACKGROUND: Acute hemorrhagic rectal ulcer (AHRU) has increasingly been reported in Japan, whereas it has rarely been reported in the English literature and is not yet established as a disease entity. The aim of this study was to elucidate clinical and endoscopic characteristics of patients with AHRU. METHODS: We enrolled 20 patients with 26 ulcers diagnosed as AHRU in our department between January 2001 and October 2005. Clinical features such as the underlying disorder, Karnofsky performance status (PS), and presence or absence of anticoagulant or antiplatelet therapy, as well as endoscopic findings and type of bleeding, were evaluated. Strategies for hemostasis were also reviewed. RESULTS: The most prevalent underlying disorder was diabetes mellitus, and the number of bedridden patients with PS 4 was relatively high. In addition, more than half of the patients had been treated with anticoagulant or antiplatelet agents. Endoscopically, ulcers were characteristically solitary and irregularly shaped, and they did not show any typical localization pattern. As a hemostatic strategy, clipping alone showed a favorable result, with a hemostatic success rate as high as 76.9%. CONCLUSIONS: This study may support the establishment of AHRU as a new clinical entity. In aged patients being treated with anticoagulant or antiplatelet agents, especially bedridden patients using aspirin, the possible appearance of this disease should be kept in mind.

Acute Disease↗
PubMed2004

Repeated gamma knife radiosurgery for multiple metastatic brain tumours.

BACKGROUND: The effectiveness of repeated gamma knife radiosurgery (GKS) for the treatment of multiple metastatic brain tumours was evaluated. METHODS: This study included 16 patients with 242 tumours, 10 men and 6 women with a mean age of 60.3 years at initial GKS, who underwent GKS four times or more for newly developed metastatic tumours. FINDINGS: Sixteen patients underwent a total of 83 GKS procedures (range 4 to 8, mean 5.2). The mean number of metastases at each GKS procedure was 2.9 and the number of tumours tended to increase at the 5th GKS procedure compared with the 1st, but not significantly. The mean interval between each procedure was 4.8 months and was not significantly different. Median survival was 22.4 months (range 9.4-78.9 months) and the primary site was not correlated with survival time. The total number of treated tumours tended to correlate to survival time, but not significantly. Use of adjuvant whole brain radiation also had no significant effect on survival time. The Karnofsky performance status was maintained at more than 70 in most patients, but decreased significantly between initial and final GKS. Death due to progression of brain lesions occurred in only about 30% of patients regardless of the multiple newly developed brain metastases. CONCLUSIONS: Repeated radiosurgery for brain metastases is effective and relatively long survival can be expected in some patients associated with a low risk of radiation-induced injury.

Adult↗
PubMed2006

Central neurocytoma: a novel appraisal of a polymorphic pathology. Our experience and a review of the literature.

Central neurocytoma should be considered in the differential diagnosis of intraventricular tumours. The records of 20 patients operated on between 1975 and 2000 for central neurocytoma were retrospectively reviewed, and the histological gradings and clinical outcomes were compared. On the basis of our previous cases, in the latter five of this series, the following therapeutic protocol was adopted. In those cases in which total removal was achieved, no further treatment was given if the MIB-1 index was <4%; vice versa, if it was >4%, a course of conformational radiotherapy was delivered. In subtotally removed cases, radiosurgery with linac was also performed (median dose 20 Gy) as well as conformational radiotherapy whenever there was a recurrence of the lesion (median dose 45 Gy). In cases in which there was only partial cytoreduction, conformational radiotherapy was administered with the adjunct of polychemotherapy if the MIB-1 was >4%. Twenty patients were surgically treated: 11 men and nine women, with an average age of 26 years (range 17 years to 42 years).Total, subtotal and partial removals were achieved in, respectively, ten, three and seven cases. At average follow-up of 7 years, 16 patients had been cured, had significantly improved or were at least stable [Karnofsky performance status score (KPS)] >70 or more)]. On the other hand, four patients had worsened; of these, two had died and two had a KPS=50 and an unfavourable prognosis. The presence of histological atypia has proved to be a significantly negative risk factor for survival (P=0.02) while an MIB score >4% was significantly correlated with an unfavourable outcome (death or worsening of neurological status). The "atypical" neurocytoma seems to be a distinct entity, with a less favourable prognosis and a higher tendency to recur.

Adolescent↗
PubMed2002

Postoperative modified stereotactic radiotherapy using a micro-multileaf collimator in patients with malignant glioma.

To achieve local control of malignant glioma, we designed a postoperative stereotactic radiotherapy using a micro-multileaf collimator (micro-MLC). The purpose of this study was to clarify the feasibility of this treatment. The treatment was performed in six patients who met the following eligibility criteria: (1) supratentorial tumor, (2) residual tumor volume < or = 40 cm3, and (3) Karnofsky performance status > or = 70. The three planning target volumes (PTVs), which consisted of restricted PTV (RPTV), intermediate PTV (IPTV), and extended PTV (EPTV), defined as the residual tumor plus a 1 cm, 2 cm, and 3 cm margins, respectively, and total dose delivery of 60-68 Gy, 52-60 Gy, and 44-52 Gy to the isocenters of RPTV, IPTV, and EPTV, respectively, in 4 Gy per fraction at five fractions per week, were established. The beam arrangement and the conformal blockade with a micro-MLC for the optimal treatment plan were designed. The treatment plans showed the high dose conformation to EPTV, the appropriate dose gradients in the three PTVs with the high dose homogeneity to RPTV, and the tolerated dose to critical structures. Following the plans, treatment was performed. The clinical findings more than 12 months after the treatment supported its possible use. We conclude that this treatment is feasible at least in selected patients.

Adult↗
PubMed2003

A first feasibility study of temozolomide for Japanese patients with recurrent anaplastic astrocytoma and glioblastoma multiforme.

BACKGROUND: The efficacy of temozolomide has been evaluated in phase I and phase II trials in patients with recurrent malignant gliomas in the United States and the European Union. We report a feasibility study of the palliative efficacy of temozolomide for patients with recurrent anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). METHODS: Sixteen patients with at least two prior chemotherapy regimens were enrolled in the study. Nine patients were confirmed to have GBM and 7 patients were confirmed to have AA at the latest pathology review, and all had a Karnofsky performance status (KPS) of over 50%. The median age was 57 years (range, 31-65 years). RESULTS: No cumulative toxicity was observed at any dose level when temozolomide was administered on a once-daily, 5-day schedule. Myelosuppression occurred, with the nadir being mid-late in the cycle (day 14 or 21). National Cancer Institute common toxicity criteria (NCI-CTC) grade 3 or 4 hematological toxicity did not occur. In the 9 GBM patients, the overall response rate (complete response + partial response [CR + PR]) was 0%. The median time to progression (TTP) was 3.5 months, and the rates of progression-free survival (PFS) at 6 and 12 months were 40% and 0%. In the 7 AA patients, the overall response rate (CR + PR) was 29% and median TTP was 9 months, while PFS rates at 6 and 12 months were 80% and 30%. CONCLUSION: The favorable safety profile and the efficacy of temozolomide in Japanese patients are not incompatible with the results seen with patients in the United States and the European Union.

Adult↗
PubMed2002

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer.

BACKGROUND: Docetaxel is highly active in the second-line treatment of patients with metastatic or unresectable locally advanced nonsmall-cell lung cancer (NSCLC). As there is a need for first-line chemotherapy that is more effective than standard platinum-based chemotherapy, this study was undertaken to evaluate the efficacy and tolerability of a docetaxel/cisplatin combination as first-line chemotherapy in advanced NSCLC. METHODS: Newly diagnosed, chemotherapy-naive patients with histologically confirmed NSCLC (measurable stage IIIB/IV NSCLC; Karnofsky performance status, 70-100; adequate bone marrow, renal, hepatic, and cardiac function) were eligible for the study. Docetaxel 75 mg/m2 was administered IV over 1 h, followed immediately by cisplatin 75 mg/m2, given IV over 30 min, with cycles repeated every 3 weeks, for up to six or nine cycles. RESULTS: Thirty-nine patients were enrolled and treated. Their median age was 59 years (range, 32-71 years) and median performance status, 90 (range, 70-100). Histologically, 23 patients (59%) had adenocarcinoma, 12 (30.8%) had squamous cell carcinoma, and 16 patients (41%) had stage IV disease. Thirty-seven patients were eligible for inclusion. In the 39 patients evaluable for safety, significant grade 3/4 toxicities included neutropenia (82%), nausea (10.3%), fatigue (10.3%), and diarrhea (7.7%). Of the 33 patients evaluable for response, 16 patients (48.5%) achieved a partial response and 7 showed progressive disease. Median overall survival time in all eligible patients was 10.5 months. CONCLUSION: Docetaxel/cisplatin produced promising response rates that compare favorably with those of current standard platinum combinations, with manageable toxicity. Further investigations of this first-line combination in NSCLC are warranted.

Adult↗
PubMed2006

[Surgical intervention in patients with malignant glioma].

Glial tumors occur at an incidence from 2 to 10/ 100.000 (Japan vs. Sweden) and building up to 50 % of all patients suffering from brain tumors. 50 % of those are again malignant gliomas Grade III and Grade IV. Despite all therapeutic approaches the median survival for glioblastomas is 15 months and for anaplastic gliomas Grade III 30 months. After diagnosis, preferably by MRI, a neurosurgical procedure is performed under microsurgical guidelines mostly by means of neuronavigation and intraoperative guidance. Depending on the preoperative diagnosis and localisation of the pathologic lesion an open craniotomy or a stereotactic biopsy is performed. This allows the histological verification and decompression and cytoreduction. A gros total safe removal preserving neurological function is the most important goal of surgery. Tumor removal in eloquent areas such as speech area is performed under local anesthesia as an awake operation. Age, Karnofsky performance status, histology as well as radical removal have a significant influence on overall survival. Adjuvant radiotherapy and chemotherapy with Temozolemide have further improved the outcome significantly. The 2-year survival has reached 28 % in most recent studies. Further experimental therapies in controlled trials, such as intratumoral convection-enhanced instillation of immunotoxins and radiopeptids, photodynamic therapy and direct instillation of new formulations of chemotherapeutic drugs (e. g. nanoparticles) are promising new approaches. New developments in the treatment of patients harboring malignant brain tumors allow an individual neurooncological treatment concept to be established to enhance overall survival and quality of life.

Brain↗
PubMed2005

Activity of carboplatin in patients with advanced non-small cell lung cancer pre-treated with a non-platinum combination.

To assess the efficacy of carboplatin when used as a single agent in patients with advanced non small cell lung cancer (NSCLC) and who are refractory to chemotherapy with a non-platinum combination, we recruited patients (n=40) NSCLC patients, 36 of whom were males, with an overall median age of 59 years (range 39-79) and Karnofsky Performance Status of 70% (range 60-90%). At baseline, the patients had a median of one disease site (range 1-3) and had received a median of one prior regimen (range 1-2). Carboplatin was administered (i.v.; AUC=6) every 3 weeks until disease progression or non-acceptable toxicity was reached. In total 169 cycles were administered (median 4 cycles/patient; range 1-8). Main toxicities were grade 2-3 anemia and grade 4 thrombocytopenia (22.5% of patients). Overall clinical response rate was 10% (4 partial responses); 26 patients (65%) had stable disease and 8 (20%) had disease progression. Median time to progression and median survival time were 90 and 187 days, respectively. One year survival rate was 13%. We conclude that carboplatin shows minimal toxicity with a discrete anti-tumor activity in patients with NSCLC and who are refractory to non-platinum combinations.

Adult↗
PubMed2005

Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study.

STUDY OBJECTIVES: The present study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin, Leucovorin and 5-FU as second line therapy, following relapse to Gemcitabine, in patients with advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Patients with advanced pancreatic cancer previously treated with Gemcitabine were included in the study. All patients had histologically or cytologically confirmed adenocarcinoma of the pancreas that was unresectable, locally advanced or metastatic. Treatment consisted of Oxaliplatin 50 mg/m(2) (2-hour iv infusion), followed by Leucovorin 50 mg/m(2) (i.v. bolus) and 500 mg/m(2) 5-FU (1-hour iv infusion), administered weekly, until unacceptable toxicity or disease progression. Objective tumour response and toxicity were evaluated according to World Health Organisation (WHO) criteria. RESULTS: A total of 30 patients, 20 men and 10 women, median age 63 years (range 52-71 years) and Karnofsky Performance Status (PS) of > or =50 entered the study. The majority of patients (96%) had locally advanced disease. A total of 380 doses of chemotherapy were delivered, a median of 12 doses per patient. Partial responses were observed in 7 patients (PR 23.3%), stable disease in 9 (SD 30.0%), while 14 patients progressed (PD 46.7%). Improved PS was observed in 18 (42.8%) patients. Patients that had responded to first-line Gemcitabine treatment were found more likely to respond or stabilize their disease with second-line treatment. The median duration of response was 22 weeks, and median overall survival was 25 weeks, Grade 3/4 toxicity expressed per chemotherapy dose included leukopenia 16%, anemia 3.2%, thrombocytopenia 3.2%, diarrhea 14.2%, fatigue 16.1% and neurotoxicity 4.2%. Eight patients (27%) suffered a febrile neutropenic event managed successfully with oral antibiotic home therapy, while 17 patients required G-CSF support. There were no treatment related deaths. CONCLUSIONS: The combination of Oxaliplatin, Leucovorin and 5-FU was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced or metastatic pancreatic adenocarcinoma, previously treated with Gemcitabine. Additional studies are warranted with this regimen in Gemcitabine relapsed pancreatic cancer patients.

Adenocarcinoma↗
PubMed2006

Gemcitabine and vinorelbine (GV) versus cisplatin, gemcitabine and vinorelbine (CGV) as first-line treatment in advanced non small cell lung cancer: results of a prospective randomized phase II study.

The objective of this study was to assess whether adding cisplatin to gemcitabine/vinorelbine combination improves the clinical outcome in patients with non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC; age < or = 75 years: Karnofsky performance status > or = 60%, and with adequate hematological, renal and hepatic function, were randomized into 2 treatment groups to receive Gemcitabine 1250 mg/m2 + vinorelbine 30 mg/m2 (GV group), or cisplatin 50 mg/m2 + gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 (CGV group). All drugs were administered on days 1 and 8 every three weeks: From September 1999 to March 2003, 114 patients were enrolled. No statistically significant difference was observed in GV vs CGV group in objective response (37 versus 47%, respectively; P = 0.5), median time to progression (5 versus 5.8 months; P = 0.6), overall survival (9 versus 10 months; P = 0.9) and 1-year survival (26 versus 28%; P = 0.9). Conversely, toxicities were significantly higher for CGV, including grade 3-4 neutropenia (24 versus 45%); neutropenic fever (4 versus 14%, including one toxic death); grade 3-4 thrombocytopenia (2 versus 14%); and grade 3-4 emesis (2 versus 14%). Our results suggest that the combination of gemcitabine and vinorelbine is less toxic than three-drug combination with cisplatin while showing similar efficacy.

Adult↗
PubMed2006

Phase II clinical and pharmacologic study of radiation therapy and carboxyamido-triazole (CAI) in adults with newly diagnosed glioblastoma multiforme.

INTRODUCTION: Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-voltage-gated calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. This study examined the efficacy, safety and pharmacokinetics of oral CAI in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) in an open-label, single arm non-randomized phase 2 trial. METHODS: Eligible patients with histologically confirmed GBM started CAI therapy (250 mg daily) on the first day of radiation (6000 cGy in 30 fractions) and continued until progression, unless side effects became intolerable. The primary outcome was survival compared to historical controls within the NABTT CNS Consortium database. Secondary outcomes included toxicity and pharmacokinetic parameters. RESULTS: Fifty-five patients were enrolled with a median Karnofsky performance status of 90 and age of 56 years. Forty-six (84%) of these patients had debulking surgeries and 52 have died. The median survival was 10.3 months (95% confidence interval (CI), 8.5-12.8) compared to 12.1 months (95% CI, 10.3-13.3) in the NABTT reference group (p = 0.97). Significant toxicities included 2 incidents of reversible vision loss. The mean CAI plasma concentration for patients taking enzyme inducing antiepileptic drugs (EIAED) was 1.35 +/-1.22 compared to 4.06 +/- 1.50 (p < 0.001) for subjects not taking these agents. Overall survival and grade > or = 3 toxicities were comparable by EIAED status. CONCLUSIONS: This study demonstrated that (1) CAI can be administered safely with concomitant cranial irradiation, (2) the pharmacokinetics of CAI are significantly affected by co-administration of EIAED, and (3) the survival of patients with newly diagnosed GBM was not improved with this novel agent, despite achieving adequate drug levels.

Administration, Oral↗
PubMed2006

A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma.

The aim of this study was to determine the antitumor activity of 17-(Allylamino)-17-demethoxyge-ldanamycin (17-AAG), a heat shock protein 90(hsp90) inhibitor in patients with metastatic papillary renal cell carcinoma (RCC) or metastatic clear cell RCC. Eligible patients were divided into 2 cohorts based on histological subtype: papillary or clear cell RCC. All patients had advanced RCC with measurable disease, a Karnofsky performance status of at least 70, and no evidence of brain metastases. Twelve patients with clear cell RCC and 8 patients with papillary RCC were treated with 17-AAG on this phase II trial. 17-AAG was given intravenously at 220 mg/m(2) twice weekly for 2 weeks followed by a week of rest. Cycle length was 21 days. No patient in either cohort achieved a complete or partial response. Toxicities included elevated liver function tests, optic neuritis, dyspnea, fatigue, and gastrointestinal side effects. Six of the 20 patients required dose reduction. At the dose and schedule used in this trial, 17-AAG did not achieve objective response in the treatment of clear cell or papillary renal cell carcinoma patients.

Aged↗