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PubMed1985

Survival and prognosis of patients with astrocytoma with atypical or anaplastic features.

This study confirms the importance of histologic tumor necrosis as a major prognostic variable in malignant glioma. Necrosis is present in glioblastoma multiforme (GBM), and absent in astrocytoma with atypical or anaplastic features (AAF). This paper evaluates 94 patients with AAF and 462 patients with GBM treated with radiation therapy with or without BCNU on 3 consecutive randomized protocols of the Radiation Therapy Oncology Group (RTOG) between 1974 and 1983. Multivariate analyses of the 556 patients confirmed histology as a significant independent variable that is prognostically relatively more important than Karnofsky performance status (KPS) and extent of surgery, and somewhat less important than age. The median survival for AAF was 36.2 months and for GBM was 8.6 months. In addition, separate multivariate analyses of AAf cases determined that the extent of surgery is a significant independent variable that is relatively more important than KPS, but less important than age. The median survival of AAF patients who underwent surgical excision was 46.8 months compared with 15.2 months for those biopsied (p less than .001).

Adolescent↗
PubMed1993

Meningiomas in elderly patients. Clinico-therapeutic considerations.

This study examines the immediate and long-term results of surgical treatment for intracranial meningioma in patients aged 65 and over. Average patient age was 69 years. The most frequent localizations were the convexity (29.8%) and the sphenoid wing (20.1%). Preoperative risk factors included hypertension (16.1%), cardiopathies (16.1%), diabetes (12.9%) pneumopathies (12.9%) and peripheral vascular diseases (9.6%). All patients were assessed according to the Karnofsky Performance Status (KPS). Operative mortality was 18.5% (23 cases). At long term follow up (minimum 4 months, maximum 12 years, average 5 years) 31.5% of patients were cured, 32.3% had improved and 4% had worsened. The risk factors that mainly influenced results included poor preoperative clinical condition as expressed by low KPS, while the most frequent medical postoperative complications that increased the rate of operative mortality were brain edema, infections and lung embolism.

Aged↗
PubMed2006

Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases.

INTRODUCTION: Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy. MATERIALS AND METHOD: We have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n = 11) and 30 Gy/10 fractions (n = 10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy. RESULTS: Prognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2- 6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0-7 months) without statistically significant differences (Log rank p = 0.74). There was one complete response and two partial responses. CONCLUSIONS: The results suggest that MST was not significantly affected by the total dose/fractionation schedule.

Adult↗
PubMed1981

Changes of adenosinetriphosphatase (ATPase) activities in lymphocytes from patients with carcinomas of the gastrointestinal tract.

The activities of both total and Oligomycin-sensitive ATPase in lymphocytes from patients with gastrointestinal tract (GI) carcinomas in different Karnofsky performance status (KPS) were determined to investigate whether or not the changes of these enzyme activities were correlated to those of the immune responsiveness of the patients. In the patients whose KPS indicated more than 50%, the mean value of the total ATPase activity in lymphocytes tended to increase slightly as compared with that determined in the control subjects, but the mean value of the Oligomycin-sensitive ATPase activity in lymphocytes tended to decrease slightly as compared with that determined in the control subjects. In the patients whose KPS indicated less than 30%, the mean values of the activities of both total and Oligomycin-sensitive ATPase in lymphocytes tended to decrease remarkably as compared with those determined in the control subjects. The ATPase activities in lymphocytes were suggested to be useful measures to the immune responsiveness of the patients with GI carcinomas.

Adenosine Triphosphatases↗
PubMedDate not supplied

Metastasis-induced acute pancreatitis in lung cancer.

Lung cancer complicated by metastasis-induced acute pancreatitis (MIAP) is rare and bears a poor prognosis. Information regarding the results of treatment and possible prognostic factors in patients with this clinical setting is limited. The records of 33 patients treated between 1976 and 2003 for histologically confirmed lung cancer complicated by MIAP were reviewed. The relevance of the interval from diagnosis of lung cancer to the occurrence of MIAP; Karnofsky performance status (KPS); white blood cell (WBC) count; levels of lactate dehydrogenase (LDH), glucose, amylase, and lipase; Ranson's score; and the duration of high amylase levels and chemotherapy to survival since MIAP were determined by univariate analysis, and their independent significance tested by multivariate analysis. Survival rates were calculated using the Kaplan-Meier method and the log-rank test. In the univariate analysis, the time interval to MIAP (P=.0484), the KPS (P=.0032), the duration of high amylase levels (P=.007), and length of chemotherapy after diagnosis of MIAP (P=.002) were significant predictors of overall survival. Ranson's score could not be used to predict clinical outcomes. Analysis of the current study indicated that duration of high amylase levels, the KPS when MIAP occurred, and the length of chemotherapy after diagnosis of MIAP are major determinants for overall survival in patients with MIAP complicated by lung cancer. These results may help to design a therapeutic approach in patients with MIAP complicated by lung cancer.

Adult↗
PubMed2004

Is early recognition of radiologically silent brain metastasis from breast cancer beneficial? A retrospective study of 22 cases.

Over a period of 10 years, twenty-two patients with T2-3N2Mx breast cancer presented with symptoms of increased intracranial pressure (ICP), but brain CT scan and/or MRI did not reveal any signs of a space occupying lesion. A brain CT scan and an MRI study were performed every 15 days. Ten patients refused this close follow up. Thus, two groups were formed group A (n = 12) included the patients who were close's followed and group B (n = 10) consisted of those patients who were not. Therefore, Group A, being under careful follow-up, initiated radiotherapy were quickly. The median time from the presentation of increased ICP symptoms until the appearance of metastases on CT and/or MRI directly followed by brain irradiation was 48 days (SE = 6.1) for group A and 72 days (SE = 0.7) for group B (p = 0.0085, log-rank test). In group A, median Overall Survival (OS) was 171.0 (SE = 21.5) days, and was 99.0 (SE = 6.3) days (p = 0.014) for group B. Volumetric analysis of the secondary brain lesions at the initiation of radiotherapy showed a total volume of metastatic lesions of 19.5 +/- 13.9 cm3 versus 65.3 +/- 20.7 cm3 for groups A and B, respectively (p < 0.001, Mann-Whitney test). Post-radiotherapy, Karnofsky Performance Status and Visual Analogue Score were also improved for group A versus B (p = 0.002). Group A appeared to benefit from close follow-up since the metastases were detected and irradiation was given sooner compared with group B, thus achieving better performance status and prolonged survival. Radiologically silent brain metastases from breast cancer should not be ignored because timely whole brain irradiation should be the goal of clinicians. Clinical suspicion should lead to close follow-up with multiple CT/MRI studies and cerebral spinal fluid cytology until the final diagnosis.

Aged↗
PubMed2000

Carcinoma of the oropharynx: local failure as the decisive parameter for distant metastases and survival.

OBJECTIVE: How important and predictive are clinical parameters and locoregional failure after radical radiotherapy of oropharyngeal carcinomas for the probability of the occurrence of distant metastases? PATIENTS AND METHODS: From 1 August 1990 to 1 October 1998, 139 patients with carcinomas of the oropharynx were treated in a prospective study by radical radiotherapy and evaluated in regard to the clinical parameters reflex-otalgia, predominant structure of tumor growth, T-category, presence of involved lymph nodes, and smoking and drinking habits. Twenty-nine patients received a concomitant chemotherapy. Twenty-five out of 139 patients had a planned neck dissection after completion of radiotherapy. Ten patients received a salvage operation. RESULTS: The median follow up time was 24 months (range, 4 to 74). Two- and 5-year overall survival rates according to Kaplan Meier were 56.1 and 49.6%. The tumors were controlled in 77/139 patients (55%). The therapy failed in 62/139 patients (45%). Both groups, 62 patients with locoregional therapy failure and 77 patients with locoregionally control led tumors, were comparable in regard to performance status (Karnofsky index), age, gender, TNM-categories, histological differentiation, drinking habits, pretherapeutic diagnostics, total dose (Gy), and number of simultaneous chemotherapy cycles. Locoregional tumor control was significantly determined by the parameters reflex-otalgia (p < 0.0078), predominant growth pattern (p < 0.012), T-category (p < 0.03), and smoking (p < 0.0285). The median survival time of patients with locoregional failure is 17 months. At this moment 81% of locoregionally controlled patients are still alive. In 14/62 patients (23%) with locoregional failure, distant metastases were detectable against 4/77 (5%) of locally controlled patients, p < 0.0026. Probability of local control and distant metastases, predominantly pulmonary, reached a plateau after 24 months. CONCLUSIONS: Locoregional tumor control, determined by several clinical parameters, is an important parameter for the probability of the development of distant metastases. Failure of local therapy is caused by the biologic aggressiveness of the tumor.

Adult↗
PubMed2000

Effect and toxicity of endoluminal high-dose-rate (HDR) brachytherapy in centrally located tumors of the upper respiratory tract.

AIM: To assess effect and toxicity of high-dose-rate afterloading (HDR) alone or in combination with external beam radiotherapy (EBRT) in centrally located tumors of the upper respiratory tract. PATIENTS AND METHODS: From 1987 to 1996, 55 patients were treated. Twenty-one patients (group A1: 17 non-small-cell lung cancer [NSCLC], A2: 4 metastases from other malignancies) were treated using HDR alone due to a relapse after external beam irradiation. In 34 previously untreated and inoperable patients (group B1: 27 NSCLC, B2: 7 metastases from other malignancies) HDR was given as a boost after EBRT (30 to 60 Gy, median 50). HDR was carried out with a 192Ir source (370 GBq). The brachytherapy dose (group A: 5 to 27 Gy, median 20; B: 10 to 20 Gy, median 15) was prescribed to 1 cm distance from the source axis. A distanciable applicator was used in 39/55 patients. RESULTS: In group A1, a response rate (CR, PR) of 53% (group B1: 77%) was reached. The median survival (Kaplan-Meier) was 5 months in group A1 (B1: 20 months). The 1-, 3- and 5-year local progression free survival rates (Kaplan-Meier) were 66% (15%), 52% (0%), and 37% (0%) in group B1 (group A1). Prognostic favorable factors in group B1 were a tumor diameter < 20 mm, the lack of radiological mediastinal involvement, a complete remission, and a Karnofsky performance status > 70. Grade-1 or 2 toxicity (RTOG/EORTC) occurred in 0% in group A and in 6% in group B. We observed no Grade-3 or 4 toxicity. Complications caused by persistent or progressive local disease occurred in 3 patients in group A (fatal hemorrhage, tracheomediastinal fistula, hemoptysis) and in 2 patients in group B (fatal hemorrhage, hemoptysis). CONCLUSIONS: HDR brachytherapy is an effective treatment with moderate side effects. In combination with external beam irradiation long-term remissions can be reached in one third of the patients.

Adult↗
PubMed2003

Multivariate analysis of prognostic factors in patients with glioblastoma.

BACKGROUND: To identify prognostic factors for overall survival in patients with newly diagnosed glioblastoma undergoing radiation therapy. PATIENTS AND METHODS: From January 1980 to June 2000, we treated 432 consecutive patients with glioblastoma at out institution. 17 patients were excluded from the analysis for various reasons. Mean age of the 415 patients who were included in the study was 59 years (19-81 years), Karnofsky performance status (KPS) was > or = 70 in 280 patients. 343 patients underwent resection, 72 had a biopsy. Various fractionation schemes were used (conventional fractionation, n = 112; hypofractionation, n = 94; accelerated hyperfractionation, n = 209). Survival probabilities were estimated using the method of Kaplan and Meier. Multivariate analysis was done with a Cox regression model. RESULTS: By July 2001, 406 patients had died. Medial overall survival was 8.2 months. Of ten factors considered in a proportional hazards model stratified for treatment (fractionation scheme and type of surgery), significant variables in a multivariate model were age (50-64 years vs < 50 years [RR 1.35; 95% CI 1.02-1.78], > or = 65 years vs < 50 years [RR 2.08; 95% CI 1.54-2.81]), performance status (KPS < 70 vs > or = 70 [RR 1.53; 95% CI 1.23-1.90]), and central tumor location (yes vs no [RR 1.39; 95% CI 1.04-1.87]). Blood hemoglobin (Hb) values were available in 318 patients and serum lactate dehydrogenase (LDH) levels in 234 patients. 89 patients were anemic (Hb men < 13 g/dl, women < 12 g/dl), in 80 patients the LDH level was raised beyond the upper limit of the normal range (> 240 U/l). By including the three significant variables, both parameters had an additional significant effect with an estimated relative risk of about 1.4 in their corresponding subgroups. CONCLUSION: Besides established prognostic factors, anemia and raised serum LDH levels may negatively influence outcome in glioblastoma patients. Our results from data-dependent modeling have to be confirmed by independent studies.

Adult↗
PubMed2003

Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?

PURPOSE: Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. PATIENTS AND METHODS: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2) carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. RESULTS: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. CONCLUSIONS: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary.

Amifostine↗
PubMed2004

Prognostic factors for brain metastases after whole brain radiotherapy. Data from a single institution.

PURPOSE: Prognostic factors for overall survival of patients treated for brain metastases with whole brain radiotherapy (WBRT) at a single institution were retrospectively evaluated, and the validity of the RTOG recursive partitioning analysis (RPA) for prognostic classes was assessed. PATIENTS AND METHODS: The data of all patients (n = 268) with brain metastases from solid tumors homogeneously treated between 01/1997 and 09/1999 at the University of Heidelberg, Germany, with WBRT without surgery or radiosurgery were reviewed. 13 different patient- and therapy-related variables were evaluated for prognosis. Second, a grouping of the study cohort was performed according to the RTOG RPA prognostic classes. RESULTS: Median survival of the whole population after the start of WBRT was 3.8 months. The 1-year survival rate was 19%. Multivariate analysis revealed that only the Karnofsky performance status, control of the primary and no extracranial disease were independent prognostic factors for overall survival. These are also the main determinants of the RTOG RPA classes. Applying the RTOG RPA classes to the authors' data set revealed three subgroups with significantly different prognosis. CONCLUSION: Based on this analysis, prognostic factors for survival after WBRT in patients with brain metastases could be identified. A total of 19% (n = 44/232) survived > or = 1 year, whereas overall survival was poor. The potential value of the RPA classes in estimating the patient's prognosis could be confirmed.

Adolescent↗
PubMed2004

Preliminary results of transarterial rhenium-188 HDD lipiodol in the treatment of inoperable primary hepatocellular carcinoma.

A multicentre study was sponsored by the International Atomic Energy Agency (Vienna) to assess the safety and efficacy of trans-arterial rhenium-188 HDD conjugated lipiodol (radioconjugate) in the treatment of patients with inoperable hepatocellular carcinoma (HCC). The radioconjugate was prepared by using an HDD (4-hexadecyl 1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) kit developed in Korea, and lipiodol. Over a period of 18 months, 70 patients received at least one treatment of radioconjugate. Some patients were re-treated if there was no evidence of disease progression. The level of radioconjugate administered was based on radiation-absorbed dose to critical normal organs, calculated following a "scout" dose of radioconjugate. The organs at greatest risk for radiation toxicity are the normal liver, the lung and the bone marrow. An Excel spreadsheet was used to determine maximum tolerated activity (MTA), defined as the amount of radioactivity calculated to deliver no more than 12 Gy to lungs, or 30 Gy to liver, or 1.5 Gy to bone marrow. These doses have been found to be safe in multiple trials using external beam therapy, but this has not been confirmed for systemically administered radiopharmaceuticals. Patients were followed for at least 12 weeks after therapy, until recovery from all toxicity. The clinical parameters evaluated included toxicity, response as determined by contrast-enhanced computed tomography, palliation of symptoms, overall survival, performance status (Karnofsky) and hepatic function (Child's classification). Liver function tests, serum alpha-fetoprotein (AFP) levels and complete blood counts were done at each follow-up visit. In the majority of patients, the scout dose studies indicated the radiation absorbed dose to normal liver to be the limiting factor to the treatment dose, while in a few patients dose to lung was the limiting factor. Radiation dose to bone marrow was negligible and was thus not a factor for the MTA calculations. Side-effects were minimal and usually presented as loss of appetite, right hypochondrial discomfort and low-grade fever, even at high levels of administered radioactivity. The symptoms resolved with simple supportive therapy within 3 days of onset. Liver function tests at 24 and 72 h showed no significant changes and complete blood counts at 1 week, 4 weeks and 12 weeks showed no changes (no bone marrow suppression). Sixteen patients were treated in the dose escalation phase of the study, when the activities administered started at 1.8 GBq (50 mCi) and rose to 7.7 GBq (206 mCi). In the efficacy phase of the study a further 54 patients were treated. Both groups of patients are included in this paper. The treatment activity of 188Re-lipiodol administered transarterially ranged from 1.8 to 9.8 GBq (50-265 mCi), with a mean activity of 4.6 GBq (124 mCi). Survival at 3 months was 90%, and at 6 months, 60%; 19% survived for 1 year. Mean survival after treatment in the total treated group of 70 patients was 9.5 months, with a range of 1-18 months. The results of this multicentre study show that 188Re-lipiodol is a safe and cost-effective method to treat primary HCC via the transarterial route. In terms of efficacy, it is potentially a new therapeutic approach for further evaluation by treatment of larger numbers of patients.

Adult↗
PubMed2004

11C-methionine PET as a prognostic marker in patients with glioma: comparison with 18F-FDG PET.

PURPOSE: The purpose of this study was to compare the prognostic value of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in glioma patients. METHODS: The study population comprised 47 patients with gliomas (19 glioblastoma, 28 others). Pretreatment magnetic resonance imaging, MET PET and FDG PET were performed within a time interval of 2 weeks in all patients. The uptake ratio and standard uptake values were calculated. Univariate and multivariate analyses were done to determine significant prognostic factors. Ki-67 index was measured by immunohistochemical staining, and compared with FDG and MET uptake in glioma. RESULTS: Among the several clinicopathological prognostic factors, tumour pathology (glioblastoma or not), age (> or =60 or <60 years), Karnofsky performance status (KPS) (> or =70 or <70) and MET PET (higher uptake or not compared with normal cortex) were found to be significant predictors by univariate analysis. In multivariate analysis, tumour pathology, KPS and MET PET were identified as significant independent predictors. The Ki-67 proliferation index was significantly correlated with MET uptake (r=0.64), but not with FDG uptake. CONCLUSION: Compared with FDG PET in glioma, MET PET was an independent significant prognostic factor and MET uptake was correlated with cellular proliferation. MET PET may be a useful biological prognostic marker in glioma patients.

Brain Neoplasms↗
PubMed2005

Retrospective study of prognostic factors in non-Hodgkin lymphoma secondarily involving the central nervous system.

The aim of this retrospective single-center study was to analyze the clinical characteristics and outcome of non-Hodgkin lymphoma (NHL) patients with central nervous system (CNS) involvement and to identify prognostic factors for survival. We searched our hospital records for NHL patients diagnosed with CNS involvement from 1982 to 2004, and 43 patients were identified. The median age was 63 years (range 23-88) and the median Karnofsky performance status was 55% (range 10-90). Treatment of CNS lymphoma included intrathecal chemotherapy in 33 patients (77%), systemic chemotherapy in 25 (58%), and radiotherapy in 16 (37%). Twenty-six patients showed a CNS response. The median survival after CNS manifestation was 5 months (range 2 days-82.5+months). Nine patients achieved long-term survival. Low lactate dehydrogenase (LDH) at CNS manifestation and a CNS response to therapy were favorable independent prognostic factors for survival in multivariate analysis (p = 0.051 and p < 0.0005, respectively), whereas a young age at initial diagnosis, initial CNS involvement, an initially normal LDH, and high-dose chemotherapy for CNS involvement were significant in univariate analysis. In conclusion, long-term survival can be achieved in patients with secondary CNS lymphoma. LDH at CNS manifestation and a CNS response to therapy were significantly associated with survival.

Adult↗
PubMed2002

A study to evaluate the pharmacokinetics of oral 5-fluorouracil and eniluracil after concurrent administration to patients with refractory solid tumours and varying degrees of renal impairment (FUMA1005).

BACKGROUND: Eniluracil is an inactivator of dihydropyrimidine dehydrogenase, the first enzyme in the catabolic pathway of 5-fluorouracil (5-FU). Concurrent administration of oral eniluracil with oral 5-FU not only increases the bioavailability of 5-FU, owing to elimination of first-pass metabolism, but can change the route of elimination of 5-FU from hepatic metabolism to renal excretion. An open-label study was performed to determine the effect of renal impairment on the pharmacokinetics of 5-FU in the presence of eniluracil. METHODS: Enrolled in the study were 17 patients with refractory solid tumours (Karnofsky performance status >/=70%; age 31-74 years; 12 male, 5 female). The patients were separated into two groups based upon creatinine clearance (CLCr): group A had "normal" renal function arbitrarily defined as CLCr >/=50 ml/min ( n=8), and group B had moderate renal impairment, i.e. CLCr <50 ml/min ( n=9). Treatment was separated into test and treatment periods. During the test period all patients received eniluracil 50 mg orally on days 1-3 and 5-FU 10 mg/m(2) together with pharmacokinetic measurements. During the treatment period, all patients received eniluracil 50 mg orally on days 1-7 with 5-FU at a standard dose of 20 mg/m(2) for those in group A or a dose individualized according to the pharmacokinetic parameters in the test period for those in group B. RESULTS: The clearance of both eniluracil and 5-FU was decreased in patients with renal impairment compared to those with normal renal function. A linear relationship was observed between 5-FU CL/F and CLCr in patients with renal impairment, but not in those with normal renal function. 5-FU dose modification, on the basis of the test dose pharmacokinetic data for the patients with renal function impairment, accurately resulted in drug exposure in the potentially therapeutic range. Toxicity was not increased. CONCLUSIONS: Eniluracil increases the oral bioavailability of 5-FU and results in a switch from hepatic metabolism to renal elimination. A standard dose of this combination can be administered safely to patients with CLCr >50 ml/min. The combination can also be given to patients with renal impairment using a test dose and pharmacokinetic measurements to predict the appropriate dose of 5-FU. It is expected that sufficient information will be available from this and other studies to allow accurate prediction of the appropriate 5-FU dose modifications required in patients with renal impairment.

Administration, Oral↗
PubMed2006

Fixed dose-rate infusion of gemcitabine in combination with cisplatin and UFT in advanced carcinoma of the pancreas.

BACKGROUND: Gemcitabine is currently considered the standard treatment for advanced pancreatic cancer (APC). Cisplatin and a fluoropyrimidine have some activity in the treatment of this cancer. The aim of this trial is to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with cisplatin and UFT in patients with APC. PATIENTS AND METHODS: Forty-six chemotherapy-naïve patients with APC that was either unresectable or metastatic were included in this phase II study. All of them had Karnofsky performance status > or =50 and unidimensionally measurable disease. Treatment consisted of gemcitabine 1,200 mg/m2 given as a 120-min infusion weekly for three consecutive weeks, cisplatin 50 mg/m2 on day 1 and oral UFT 400 mg/m2/day (in two to three daily doses) on days 1 to 21; cycles of treatment were given every 28 days. RESULTS: A total of 208 cycles of chemotherapy were given with a median of 4 per patient. Fourteen patients (30%) achieved partial responses (95% CI 19-48%) and 17 (37%) had stable disease. The median time to progression was 5 months, and the median overall survival 9 months. Nineteen patients (49%; 95% CI 32-64%) had a clinical benefit response. Grade 3-4 WHO toxicities were as follows: neutropaenia in 26 patients (57%), with 5 cases of febrile neutropaenia (11%), thrombocytopaenia in 15 (33%), anaemia in six (13%), diarrhoea in 5 (11%), asthenia in 2 (4%) and mucositis in 1 (2%). Seven patients required hospitalisation for treatment-related complications. CONCLUSION: A fixed dose-rate infusion of gemcitabine associated with cisplatin and UFT is active in patients with APC, though at the cost of considerable toxicity.

Adult↗
PubMed1996

Phase I and pharmacologic study of 7- and 21-day continuous etoposide infusion in patients with advanced cancer.

PURPOSE: This phase I study was undertaken to evaluate the safety and tolerability of prolonged infusional etoposide, and to evaluate its pharmacokinetic/pharmacodynamic profile in patients with advanced cancer. METHODS: A group of 17 patients received a 7-day infusion of etoposide (schedule A) every 21 days at doses from 30 to 75 mg/m2 per day, and a second group of 37 patients a 21-day infusion (schedule B) every 28 days at doses from 18 to 40 mg/m2 per day. Patients had a median Karnofsky performance status (PS) of 80%, and 34 patients had no prior chemotherapy. Etoposide concentrations at steady state (Css) and other pharmacokinetic parameters (plasma clearance, CLp; area under the curve, AUC) were determined during the first treatment cycle. Correlation coefficients were calculated to measure the relationship between variables. RESULTS: Myelosuppression was the major toxicity, and was associated with three deaths. The maximum tolerated dose due to neutropenia was 75 mg/m2 per day for schedule A and 40 mg/m2 per day for schedule B. There was significant interpatient pharmacokinetic variability in both infusional schedules. Even though etoposide dose levels did not significantly correlate with plasma levels, the Css was > or = 1 microgram/ml in the majority of the patients. A significant correlation between AUC and neutrophil absolute decrease was noted only in schedule B (r = 0.56, P = 0.003). There were several marginal relationships in schedule B: PS versus Css (r = 0.31, P = 0.058), PS versus AUC (r = -0.38; P = 0.058) and age versus CLp (r = -0.31, P = 0.057). CONCLUSION: Overall, significant correlations were found for several hematologic variables and etoposide dose levels, but not with the Css values. One major problem with the application of pharmacodynamic models to predict hematologic toxicity in clinical practice is the presence of significant interpatient variability.

Adult↗
PubMedDate not supplied

Comparison of chemotherapy response with P-glycoprotein, multidrug resistance-related protein-1, and lung resistance-related protein expression in untreated small cell lung cancer.

The aim of this study was to investigate the expression of P-glycoprotein (Pgp), multidrug resistance-related protein-1 (MRP1), and lung resistance-related protein (LRP) in response to chemotherapy in untreated small cell lung cancer (SCLC). Immunohistochemical analyses were performed on multiple nonconsecutive sections of biopsy specimens to detect Pgp, MRP1, and LRP expression in 40 patients with SCLC before chemotherapeutic induction. Response to chemotherapy was evaluated by clinical and radiological methods. The patients were divided into a good response group (n = 20) and a poor response group (n = 20). No significant differences in prognostic factors (Karnofsky performance status, tumor size, or tumor stage) were found between the two groups of patients. The difference in positive Pgp and MRP1 expressions between the good and poor response groups was significant. However, the difference in LRP expression was not significant. We conclude that chemotherapy response of patients with SCLC was related to either Pgp or MRP1 but not LPR expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗