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PubMed1999

Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma.

PURPOSE: To identify prognostic factors and a model predictive for survival in patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 670 patients with advanced RCC treated in 24 Memorial Sloan-Kettering Cancer Center clinical trials between 1975 and 1996. Clinical features were first examined univariately. A stepwise modeling approach based on Cox proportional hazards regression was then used to form a multivariate model. The predictive performance of the model was internally validated through a two-step nonparametric bootstrapping process. RESULTS: The median survival time was 10 months (95% confidence interval [CI], 9 to 11 months). Fifty-seven of 670 patients remain alive, and the median follow-up time for survivors was 33 months. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status (<80%), high serum lactate dehydrogenase (> 1.5 times upper limit of normal), low hemoglobin (< lower limit of normal), high "corrected" serum calcium (> 10 mg/dL), and absence of prior nephrectomy. These were used as risk factors to categorize patients into three different groups. The median time to death in the 25% of patients with zero risk factors (favorable-risk) was 20 months. Fifty-three percent of the patients had one or two risk factors (intermediate-risk), and the median survival time in this group was 10 months. Patients with three or more risk factors (poor-risk), who comprised 22% of the patients, had a median survival time of 4 months. CONCLUSIONS: Five prognostic factors for predicting survival were identified and used to categorize patients with metastatic RCC into three risk groups, for which the median survival times were separated by 6 months or more. These risk categories can be used in clinical trial design and interpretation and in patient management. The low long-term survival rate emphasizes the priority of clinical investigation to identify more effective therapy.

Adult↗
PubMed2003

Activity of weekly irinotecan (CPT-11) in patients with advanced non-small cell lung cancer pretreated with platinum and taxanes.

Irinotecan (CPT-11), a semisynthetic derivative of camptothecin, is active in the treatment of non-small cell lung cancer (NSCLC). In this report we describe our experience with this drug when used as a single agent in patients with advanced NSCLC refractory to chemotherapy with platinum and taxanes. Nineteen NSCLC patients (thirteen males and six females; 53% adenocarcinoma and 26% squamous cell carcinoma) with a median age of 52 years (range 34-71) and a Karnofsky performance status of 60% (60-80%) were included in the study. At baseline, the patients had a median of two disease sites and had been treated with a median of two prior regimens. Irinotecan was given at a dose of 100 mg/m(2) i.v.) weekly for 4 weeks followed by 1 week of rest. A total of 123 weekly infusions were administered, and each patient received a median of 4 weeks of treatment (range 1-32). All patients were evaluated by intention-to-treat analysis for efficacy and safety. Main toxicities reported were grade 3 neutropenia (10% of patients), diarrhea (10% of patients), and grade 4 thrombocytopenia (5% of patients). The overall clinical response rate was 16% (95% CI: 8-24) with three partial responses and 9 (47%) patients with stable disease. The median time to progression and the median survival time were 7 and 15 weeks, respectively. In conclusion, weekly irinotecan showed antitumoral activity and minimum toxicity in NSCLC patients refractory to platinum and taxanes.

Adult↗
PubMed2005

The correlation between fatigue, physical function, the systemic inflammatory response, and psychological distress in patients with advanced lung cancer.

BACKGROUND: Functional disability is reported frequently in fatigued cancer patients, but little is known about the correlation between fatigue and objective physical function. In addition, from previous work, the systemic inflammatory response and psychological distress appear to be related to fatigue. METHODS: Thirty-eight patients with metastatic or locally advanced lung carcinoma and 15 age-matched and gender-matched, healthy controls completed the Functional Assessment of Chronic Illness Therapy-Fatigue scale, a visual analogue weakness score, and the Hospital Anxiety and Depression (HAD) scale. Hemoglobin concentrations, C-reactive protein (CRP) concentrations, creatine kinase concentrations, white blood cell count, body composition, Karnofsky performance status (KPS), grip strength, and chair-rise time also were measured in both groups. The cancer patients were then grouped into tertiles on the basis of fatigue scores. RESULTS: The cancer patients had greater fatigue compared with the control group (P < 0.001). They also weighed less, had lower hemoglobin and creatine kinase levels and higher CRP levels, and had lower KPS, poorer grip strength, longer chair-rise times, and increased HAD scale scores (all P < 0.01). KPS and chair-rise time were correlated strongly (r(2) = 0.565; P < 0.001). With increasing fatigue, KPS was lower, and chair-rise time and HAD scale scores were greater (P < 0.01). On multiple regression analysis, only KPS, weakness, and HAD scale scores were correlated independently with fatigue (r(2) = 0.570; P < 0.001). CONCLUSIONS: Objective physical function (as measured by chair-rise time) in patients with advanced lung cancer was poorer with increasing fatigue. Results of the current study suggest that fatigue is not a result primarily of weight loss or anemia but is related to KPS and psychological distress.

Adult↗
PubMed2004

Combined irinotecan and oxaliplatin in patients with advanced pre-treated pancreatic cancer.

OBJECTIVES: This study evaluated the clinical activity and toxicity of combination chemotherapy with irinotecan and oxaliplatin in patients with advanced pancreatic cancer that had progressed despite > or =1 course of a gemcitabine-containing regimen. METHODS: Thirty patients with metastatic pancreatic cancer and Karnofsky performance status > or =70 received oxaliplatin 60 mg/m2 on days 1 + 15 and irinotecan 60 mg/m2 on days 1 + 8 + 15 every 4 weeks. Patients were assessed on the basis of clinical benefit response, changes in serum tumour marker CA 19-9, objective tumour response, time to progressive disease (TTP), and survival. RESULTS: Six patients (20%) had clinical benefit response (median duration of 7.2 months). CA 19-9 levels were reduced > or =50% from baseline in 8 patients (26%) and remained stable in 8 patients. CT scans revealed that 3 patients (10%) had a partial response and 7 (23%) had stable disease. Two patients (7%) were down-staged and underwent surgery. Median TTP was 4.1 months, median survival was 5.9 months and the 1-year survival rate was 23.3%. The most serious adverse events were grade 3-4 leukopenia in 2 patients (6%), grade 3 neuropathy in 2 (6%) and grade 3 diarrhoea in 1 (3%). CONCLUSION: Chemotherapy with irinotecan and oxaliplatin is an active and well-tolerated combination in patients with advanced pre-treated pancreatic cancer.

Adenocarcinoma↗
PubMed1998

Thymoma: prognostic factors and treatment outcomes.

BACKGROUND: The objective of this study was to establish prognostic factors for thymoma and determine the impact of surgery with or without postoperative radiotherapy. METHODS: Seventy patients treated at the University Hospital Düsseldorf during the period 1954-1991 were retrospectively studied. All thymoma patients underwent surgery, 22 received postoperative radiotherapy, and 3 also received chemotherapy. According to thymoma staging as described previously by Masaoka et al., 21% were Stage I, 26% Stage II, 43% Stage III, 7% Stage IVA, and 3% Stage IVB. Lymphocytic type disease was found in 36% of patients, lymphoepithelial type in 33%, epithelial type in 23%, and spindle cell type in 9%. The relevance of Karnofsky performance status (KPS), gender, age, myasthenia gravis, histology, tumor size, and stage to survival was determined by univariate analysis, and their independent significance was tested by multivariate analysis. Survival rates were calculated using the Kaplan-Meier method and the log rank test. RESULTS: In univariate analysis, KPS (P < 0.001), histologic type (P=0.0093), and stage (P=0.0001) proved to be significant predictors of overall survival. Spindle cell type was associated with the best and epithelial type the worst prognosis; patients with the latter type had a 5-year survival rate of 30%. Multivariate analysis revealed that stage, histology, and KPS were predictive of overall survival. In Stages III and IV, relapses were reduced by postoperative radiotherapy from 50% to 20%. The site of relapse was outside the irradiated area in 80% of patients. Disease free survival (P=0.36) and median survival (P=0.72) of patients with completely resected advanced thymomas did not differ from that for patients with incompletely resected tumors who received radiotherapy. CONCLUSIONS: Postoperative radiotherapy can improve local control in patients with advanced thymoma. Survival after incomplete resection is not compromised when postoperative radiotherapy is employed. KPS should be considered an important prognostic factor in future studies.

Adolescent↗
PubMed1996

Autologous bone marrow harvesting in outpatients.

STUDY OBJECTIVE: To assess the experience with autologous bone marrow harvesting in outpatients. DESIGN: Retrospective analysis of outpatients who underwent autologous bone marrow harvesting from 1990 to 1992. SETTING: University-affiliated surgical day hospital. SUBJECTS: 235 outpatients who underwent 264 autologous bone marrow harvests. Patients are candidates for autologous bone marrow harvesting on an outpatient basis if they are Karnofsky performance status of 80-100 and ASA status I, II or III. MEASUREMENTS AND MAIN RESULTS: The incidence of perioperative complications and hospital admission from the Surgical Day Hospital, the duration of the harvesting procedure and postanesthesia care unit (PACU) stay, details of the postoperative pain management, and costs and charges of the outpatient procedure compared with the same procedure performed on inpatients were assessed. Mean age was 37.7 years +/- 10.5 SD; + 7.7% patients were male and 52.3% were female. The disease process included non-Hodgkin's lymph/ma (30.3%), leukemia (24.3%), metastatic breast cancer (18.4%), Hodgkin's disease (17.3%), testicular carcinoma (6.5%) and other (1.6%). The patients were ASA status II (54.5%) or ASA III (45.5%) and received general endotracheal anesthesia. Each patient had 10.7 ml/kg +/- 2.8 SD of marrow harvested over a period of 110.7 minutes + 30.4 SD and total recovery room time of 233.7 minutes +/- 85.5 SD. Of 251 harvest, only three (1.1%) required hospital admission. PACU complaints included transient hypotension and dizziness (5.3%), nausea (3.8%), vomiting (3.4%), and (1.9%) temperature elevation. 83.7% of patients were reached at home the following day and 4.1% complained of nausea and/or vomiting at home. 6.8% of patients experienced temperature elevation at home. Only 27.1% of patients took the acetaminophen with codeine that was prescribed. The reminder required no opioid at home. Outpatient charge/ inpatient charge was 51.1%, and outpatient cost/inpatient was 74.4%. CONCLUSION: Autologous bone marrow harvesting is an acceptable ambulatory surgical procedure that results in a very law postanesthesia complication rate. Postoperative pain is easily controlled. The outpatient setting offers cost and time advantages to the patient.

Adult↗
PubMed1997

Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients.

Cancer anorexia-cachexia syndrome (CACS), which is characterized by progressive weight loss (WL) and anorexia (A), is present in 50% of advanced cancer patients and in 80% of terminally ill cancer patients. One of the most controversial aspects of CACS is its oetiopathogenesis; experimental studies have identified certain cytokines [Tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and gamma interferon (gamma-IFN)] as possible co-factors in the onset of the syndrome. The aim of our study was to investigate the correlation between serum levels of circulating cytokines and severity of CACS. The following series of parameters was identified in 61 patients with advanced and terminal cancer: stage of disease; Karnofsky performance status (KPS) and clinical symptoms; biohumoral, anthropometric and immunological situation; level of circulating cytokines. All these parameters were evaluated for a possible link with WL/A. Our data do not show any significant correlation between circulating cytokines and WL/A. A direct correlation was identified between WL/A and nausea (P = 0.03 and P < 0.001, respectively) whereas inverse correlations were observed for both factors as regards arm circumference (P < 0.001 for both), wrist circumference (P < 0.001 for both), KPS (P < 0.001 and P = 0.003, respectively) and creatinine (P = 0.005 and P = 0.03, respectively). Other biochemical factors, such as haemoglobin, haematocrit, glycaemia, prealbumin, sodium and chlorine were also correlated with at least one of two clinical parameters in question. Unexpected results were seen in the increases in CD20 and CD4 and in the CD4/CD8 ratio. Serum levels of these cytokines do not, therefore, appear to be critical in the onset of CACS. On the contrary, our findings confirmed the clinico-laboratory picture that is characteristic of CACS. If we consider the possibility that CACS is provoked by an aspecific response of the host's defence mechanisms against prolonged neoplastic attack, the increase in CD4 (helper lymphocytes) could be linked to the persistent response.

Adult↗
PubMed2000

Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small-cell lung cancer (LA-NSCLC): identification of five groups with different survival.

PURPOSE: Survival of patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) is predicted by the stage of the disease and other characteristics. This analysis was undertaken to identify these characteristics in a large cooperative group patient population, as well as to define subgroups of the population with differing outcomes. PATIENTS AND METHODS: Analysis included 1,999 patients treated in 9 RTOG trials between 1983 and 1994 with thoracic irradiation (RT) with (n = 355) or without chemotherapy (CT). RESULTS: In univariate analysis, the following characteristics were significantly associated with an improved survival: use of CT, CT delivered without major deviation, abnormal pulmonary function tests, normal hemoglobin, protein, LDH and BUN, presence of dyspnea, hemoptysis, cough or hoarseness, uninvolved lymph nodes, T1 or T2 stage, no malignant pleural effusion (PE), weight loss of < 8%, Karnofsky performance status (KPS) of at least 90, adenocarcinoma histology, female gender, and age less than 70 years. Recursive partitioning analysis (RPA) was subsequently applied to identify 5 patient subgroups with significantly different median survival times (MST): Group I, KPS of > or = 90, who received chemotherapy (MST 16.2 months); Group II, KPS of > or = 90, who received no CT, but had no PE (MST 11.9 months); Group III, KPS < 90, younger than 70 years, with non-large cell histology (MST 9.6 months); Group IV, KPS > or = 90, but with PE, or KPS < 90, younger than 70 years, and with large cell histology, or older than 70 years, but without PE (MST 5.6-6.4 months); Group V, older than 70, with PE (MST 2.9 months). CONCLUSION: Cisplatinum-based CT improves survival, for excellent prognosis of LA-NSCLC patients, over RT alone. The presence of a malignant pleural effusion is a major negative prognostic factor for survival. The identification of RPA prognostic groups among patients with LA-NSCLC provides prognostic information and may serve as a basis of stratification in future trials.

Adenocarcinoma↗
PubMed2004

Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.

PURPOSE: To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). PATIENTS AND METHODS: One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). RESULTS: All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P =.57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, -13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P =.63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (chi(2) test, P =.02). CONCLUSION: There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

Adrenal Cortex Hormones↗
PubMed1995

Hyperfractionated radiotherapy combined with simultaneous chemotherapy in inoperable non-small cell lung cancer: a pilot study.

Between March 1992 and February 1993, hyperfractionated radiotherapy (HRT) (1.2 Gy.fraction-1, twice a day, total dosage of 69.6 Gy) and simultaneous cisplatin (70 mg.m-2, 3rd and 23rd days of HRT) and etoposide (70 mg.m-2, 1-3rd and 20-23rd days of HRT) were applied to 27 patients with inoperable non-small cell lung cancer (NSCLC). Their Karnofsky performance statuses were 70-90%, and mean age was 52 (36-63). Two cases were stage II (one of the patients refused the operation and the other was medically inoperable because of insufficient ventilation), eight were stage IIIA and 17 were stage IIIB. No severe life-threatening grade IV acute toxicity findings were observed. Generally, acute side-effects were transient and did not require discontinuation of treatment. Tumour responses were as follows: complete response in six cases (23%); partial response in 19 cases (70%); and stable disease in two (7%). When complete response rates were compared according to stage, histological type, age group and weight loss, no statistically significant difference was found. Median overall and disease-free survival times were 14 months (95% confidence interval) (95% CI) 11-17 months and 10 months (95% CI 7-13 months), respectively. Twelve and 24 months overall and disease-free survival rates were 56 and 30%, and 36 and 24% respectively. No statistically significant difference was found in overall survival rates among epidermoid and nonepidermoid types, while the difference in disease-free survival was statistically significant. The acute and late complications of our HRT and simultaneous chemotherapy protocol were tolerable and the survival rates were encouraging.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

A preliminary outcome analysis of the Patterns of Care Study in Japan for esophageal cancer patients with special reference to age: non surgery group.

BACKGROUND: The Patterns of Care Study (PCS) was imported to Japan from the United States in July 1996. A preliminary outcome analysis of the PCS for esophageal cancer patients in Japan was made with special reference to age, because the elderly population is rapidly increasing in Japan. PATIENTS AND METHODS: From July 1996 to February 1998, external PCS audits were performed for 37 institutions nationwide and detailed information of 561 esophageal cancer patients treated during the period 1992-1994 was collected by using the fifth PCS data format developed in the United States. This format was provided courtesy of the American College of Radiology. For this study, patients who had not undergone surgery (n = 336) were selected. The patients were classified into three age groups: < 65 years old (n = 119), between 65 and 74 years (n = 93), and 75 years or older (n =123). Cox's proportional hazards model was used for the statistical analysis, with survival, acute/subacute complication and late complication of grade 3 or more based on RTOG criteria, as the endpoints. RESULTS: Significant prognostic factors for the entire non-surgery group were Karnofsky Performance Status (KPS) (p = 0.0007), stage (p = 0.0001), and external irradiation dose (p = 0.0001). For the younger group, KPS (p = 0.0004), stage (p = 0.0197), and utilization of brachytherapy (p = 0.0010) were significant, while for the intermediate age group it was KPS (p = 0. 0027), history of pulmonary disease (p = 0.0339), stage (p = 0.0001), and external dose (p = 0.0001), and for the elderly group, stage (p = 0.0001) and external irradiation dose (p = 0.0224) were significant. Significant risk factors for complications for the entire group were stage (p = 0.0411), external dose (p = 0.0163), and stratification of institution (academic vs. nonacademic) (p = 0. 0114). Significant risk factors for the younger group were history of pulmonary disease (p = 0.0495) and external dose (p = 0.0037), and the other age groups showed no significant risk factors. CONCLUSION: Age was not a significant prognostic or risk factor for esophageal cancer patients in the non-surgery group treated with radiation therapy. Therefore, radiation therapy represented an important treatment modality for the elderly as well as for the younger esophageal cancer patients. External dose was a treatment-related prognostic factor for the elderly as well as for the intermediate age group.

Adenocarcinoma↗
PubMed1993

Neuroendocrine differentiation as a prognostic factor in non-small cell lung cancer.

The prognostic value of clinical and pathological factors in 97 patients with non-small cell lung cancer (NSCLC), were analyzed through immunohistochemical methods. The impact on response rate and survival of age, Karnofsky performance status (PS), sex, NSCLC subtype and grade, extent of disease, objective chemotherapy response, LDH values, metastatic sites involved and immunohistochemical markers of neuroendocrine differentiation (neuron specific enolase (NSE), synaptophysin (Sy 38), chromogranin (Chr A) and Leu-7) were analyzed. Median age was 61 years and seven patients were women. Histologically, 58 had squamous cell carcinoma, 28 adenocarcinoma and 11 large cell undifferentiated carcinoma. One patient had Stage II, 35 Stage IIIa, 19 Stage IIIb and 42 Stage IV. Six patients achieved complete response, 18 partial response, 34 stable disease and 39 progressive disease. NSE was negative in 54.3% of cases as was Sy 38 (77.4%), Chr A (97.8%) and Leu-7 (95.8%). We have found correlation between neuroendocrine differentiation and absence of P-Glycoprotein expression; patients included in this subset had a higher response rate but no evidence of longer survival. The univariate analysis showed that four parameters had significant adverse effect on survival: non-responders, poor PS, abnormal LDH value and absence of NSE expression. Multivariate analysis showed that the best combination of independent prognostic factors in predicting survival was: PS and NSE expression by immunohistochemical methods.

Adult↗
PubMed2006

Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma.

PURPOSE: TM-601 binds to malignant brain tumor cells with high affinity and does not seem to bind to normal brain tissue. Preclinical studies suggest that iodine-131 (131I) -TM-601 may be an effective targeted therapy for the treatment of glioma. We evaluated the safety, biodistribution, and dosimetry of intracavitary-administered 131I-TM-601 in patients with recurrent glioma. PATIENTS AND METHODS: Eighteen adult patients (17 with glioblastoma multiforme and one with anaplastic astrocytoma) with histologically documented recurrent glioma and a Karnofsky performance status of > or = 60% who were eligible for cytoreductive craniotomy were enrolled. An intracavitary catheter with subcutaneous reservoir was placed in the tumor cavity during surgery. Two weeks after surgery, patients received a single dose of 131I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg of TM-601), each labeled with 10 mCi of 131I. RESULTS: Intracavitary administration was well tolerated, with no dose-limiting toxicities observed. 131I-TM-601 bound to the tumor periphery and demonstrated long-term retention at the tumor with minimal uptake in any other organ system. Nonbound peptide was eliminated from the body within 24 to 48 hours. Only minor adverse events were reported during the 22 days after administration. At day 180, four patients had radiographic stable disease, and one had a partial response. Two of these patients further improved and were without evidence of disease for more than 30 months. CONCLUSION: A single dose of 10 mCi 131I-TM-601 was well tolerated for 0.25 to 1.0 mg TM-601 and may have an antitumoral effect. Dosimetry and biodistribution from this first trial suggest that phase II studies of 131I-TM-601 are indicated.

Adult↗
PubMed2004

Superiority of letrozole to tamoxifen in the first-line treatment of advanced breast cancer: evidence from metastatic subgroups and a test of functional ability.

PURPOSE: The letrozole study 025 is a large (n = 907), international, double-blind, randomized, phase III trial in postmenopausal women with advanced breast cancer. This subanalysis compares the efficacies of letrozole and tamoxifen as first-line therapy in postmenopausual women with advanced breast cancer according to site of metastatic lesions and Karnofsky Performance Status (KPS). MATERIALS AND METHODS: Nine hundred seven patients with advanced breast cancer were randomly assigned to once-daily oral letrozole (2.5 mg; Femara; Novartis Pharma AG; Basel, Switzerland) or tamoxifen (20 mg; Tamofen; Leiras OY; Turku, Finland). Time to progression (TTP) was estimated using the Kaplan-Meier product-limit method. Treatments were compared by Cox proportional hazards regression models. RESULTS: Letrozole treatment significantly prolonged TTP in all subsets of patients: those with nonvisceral metastases, those with visceral metastases without liver involvement, and those with liver metastases. The reduction in risk of progression ranged from 25%, for patients with nonvisceral metastases, to 36%, for patients with liver metastases. The distributions of baseline KPS scores for both treatment groups were similar (57% had KPS scores >/=90). Time to worsening of 20 points or more in KPS score was significantly longer with letrozole than with tamoxifen, but modest numbers of patients experienced such deterioration (letrozole, 20%, tamoxifen, 22%, in patients without visceral metastases; 23%-24% in patients with liver metastases; and letrozole, 14%, tamoxifen, 30%, in patients with visceral metastases without liver involvement). CONCLUSION: These data demonstrate the consistent superiority of letrozole over tamoxifen and support the use of letrozole as a new standard of endocrine therapy in postmenopausal women with advanced breast cancer.

Adult↗
PubMed2005

Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy.

Based on the activity of menadione (M) in the human tumor stem cell assay, we conducted a phase I trial of M in patients with advanced cancer. Forty patients (19 men, 21 women) were treated with 90 courses of M; 82 treatment courses are evaluable for toxicity. The median patient age, Karnofsky performance status, and number of prior chemotherapy regimens were 61 years (range 32-74 years), 80% (range 50-100%), and two, respectively. M was given by a short (1-5 h) intravenous infusion every 3 weeks, starting at 40 mg/m2 and escalating by modified Fibonacci scheme to 1360 mg/m2. Toxicity was graded according to the Southwest Oncology Group toxicity scale with defined hypersensitivity reaction (HSR) scales. No grade > or =2 hematologic toxicity was observed. Non-hematologic toxicity consisted of a HSR syndrome of paresthesiae of the extremities, facial flushing, burning of the eyes and mucous membranes, chest pain and dyspnea. HSR was defined as Grade I toxicity by the presence of facial numbness, flushing, and/or a tingling sensation or burning of the eyes and mucous membranes. Grade II toxicity was defined as the presence of the same above symptoms plus chest tightness, paresthesiae of extremities and/or dyspnea and chest pain. These toxicities were grade 1 in 3 of 4 patients at a dose of 840 mg/m2. At 1360 mg/m2, 2 of 13 patients suffered grade 1 HSR and 7 of 13 grade 2 HSR. No objective partial or complete responses were observed. Plasma menadione concentrations peaked at 1.9-7.4 microM during the infusion in 3 patients receiving 1360 mg/m2. Further phase 1 and 2 combination trials using longer infusion durations have resulted from this trial.

Adult↗
PubMed1999

Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: A retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy.

PURPOSE: To determine any differences in outcome for patients with anaplastic astrocytoma (AA) treated with adjuvant carmustine (BCNU) versus procarbazine, lomustine, and vincristine (PCV) chemotherapy. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) database was reviewed for patients with newly diagnosed AA treated according to protocols that included either BCNU or PCV adjuvant chemotherapy. All patients were treated with radiation therapy. The outcome analysis included overall survival, taking into account patient age, extent of resection, Karnofsky performance status (KPS), and treatment group (BCNU v PCV). Stratified and nonstratified Cox proportional hazards models were used, as well as an analysis using matched cases between the groups. RESULTS: A total of 257 patients were treated with BCNU according to RTOG protocols 70-18, 83-02, and 90-06; 175 patients were treated with PCV according to RTOG protocol 94-04. All pretreatment characteristics except KPS were well balanced by treatment group; 61% of the BCNU group had a KPS of 90 to 100 compared with 73% of the PCV group (P =.0075). No statistically significant difference in survival was observed in any age group or by KPS or extent of surgery. The stratified analysis also showed no trends for improved survival by treatment group (P =. 40). The Cox model identified only age, KPS, and extent of surgery as important variables influencing survival, not treatment group. Matching cases between groups using age, KPS, and surgery resulted in 133 matched pairs. No difference in survival was observed (P =. 41). In a Cox model in which each matched pair is a strata, there was no difference between groups (P =.20). CONCLUSION: Using this retrospective analysis, there does not seem to be any survival benefit to PCV chemotherapy. Future phase III studies for patients with AA may need to consider whether BCNU or PCV is used in the control arm.

Adult↗
PubMed2003

Recursive partitioning analysis (RPA) class does not predict survival in patients with four or more brain metastases.

BACKGROUND: We evaluated prognostic factors for survival in patients with four or more brain metastases in order to determine whether intense local treatment might be justified for some of them. If up to three brain metastases are present, surgical resection or radiosurgery are currently being considered in case of favorable prognostic factors. PATIENTS AND METHODS: Retrospective intention-to-treat analysis of 113 patients who underwent whole-brain radiotherapy without surgical resection or radiosurgery at a single institution. Standard treatment was given with ten fractions of 3 Gy. Higher total doses were administered in 13% of patients. Recursive partitioning analysis (RPA) prognostic classes have been described by the Radiation Therapy Oncology Group (RTOG) in 1997 (class I: Karnofsky performance status [KPS] > or = 70%, age < or = 65 years, no extracranial metastases, controlled primary tumor; class III: KPS < 70%; class II: others). RESULTS: Median number of brain metastases was six (four to 50). Most patients (69%) had extracranial metastases as well. Criteria of RPA Class I (II) were met in 4% (41%), whereas 56% had KPS < 70% and thus were grouped into class III (Tables 1 and 2). Complete or partial remission of brain metastases was found in 46% of patients who underwent computed tomography. Median survival was 4 months, 1-years survival rate 15%. Only age was a borderline significant prognostic factor in univariate analysis (< or = 50 years vs > 50 years, p = 0.05). Strong trends were found for KPS, extracranial metastases, control of the primary tumor, and breast primary tumor. Number of brain metastases, RPA class and treatment-related factors such as total dose or remission of brain metastases had no appreciable influence on survival (Figure 1). Multivariate analysis failed to identify any significant prognostic factor. CONCLUSIONS: Patients with four or more brain metastases seem to represent a group with unfavorable prognosis where remission of brain metastases or administration of more than 30 Gy were not associated with increased survival. The number of patients in RPA class I was too small to draw final conclusions. However, there was absolutely no survival difference between patients in class II (median survival 3.6 months) and III (median 4.2 months).

Adult↗
PubMed2000

Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumor status, presence of extracranial system metastases, and age. An analysis of RTOG 91-04, a randomized study comparing two dose-fractionation schemes with a comparison to the established RTOG database, was considered important to validate the RPA classes. METHODS AND MATERIALS: A total of 445 patients were randomized on RTOG 91-04, a Phase III study of accelerated hyperfractionation versus accelerated fractionation. No difference was observed between the two treatment arms with respect to survival. Four hundred thirty-two patients were included in this analysis. The majority of the patients were under age 65, had KPS 70-80, primary tumor controlled, and brain-only metastases. The initial RPA had three classes, but only patients in RPA Classes I and II were eligible for RTOG 91-04. RESULTS: For RPA Class I, the median survival time was 6. 2 months and 7.1 months for 91-04 and the database, respectively. The 1-year survival was 29% for 91-04 versus 32% for the database. There was no significant difference in the two survival distributions (p = 0.72). For RPA Class II, the median survival time was 3.8 months for 91-04 versus 4.2 months for the database. The 1-year survival was 12% and 16% for 91-04 and the database, respectively (p = 0.22). CONCLUSION: This analysis indicates that the RPA classes are valid and reliable for historical comparisons. Both the RTOG and other clinical trial organizers should currently utilize this RPA classification as a stratification factor for clinical trials.

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