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M Glantz

Publications and source records attributed to M Glantz.

17 recordsLinked to original sources
PubMed2003

Quantitative measurement of quality outcome in malignant glioma patients using an independent living score (ILS). Assessment of a retrospective cohort.

PURPOSE: Although a number of tools have been developed to measure 'quality of life' in patients with malignant glioma, there remains no completely satisfactory technique that incorporates a quality of life measure into survival analysis. We propose that a patient's ability to maintain independent activity offers a way to accomplish this goal. PATIENTS AND METHODS: An independent living score (ILS) is generated by awarding points on a monthly basis based on Karnofsky score and weighing the score based on the particular month of the clinical course. The ILS has a large range for any given survival, and can discriminate important treatment effects to which standard survival analyses are completely insensitive. Using this score and several variations, we were able to retrospectively analyze a patient cohort to assess what correlated with ILS. RESULTS: We found a strong correlation with survival of all the measures tested. Interestingly, we found that patients for whom a total resection was performed and those who were most intensively treated had significantly higher ILS values, suggesting that not only did more aggressive treatment improve survival but that it did not simply increase survival at the expense of the time a patient remained independent. CONCLUSION: Since the general course for patients with malignant glioma is one of increasing disability and loss of independence, we feel that these measures can serve as a way to distinguish between those therapies that increase survival at the expense of quality of life versus those that do not. Consideration should be given to incorporating these measures into prospective trials.

Activities of Daily Living↗
PubMed2000

Positive CSF HSV PCR in patients with GBM: a note of caution.

Because two patients with temporal lobe glioblastomas had herpes simplex (HSV) DNA detected in CSF using PCR at the time of their presentation, we reviewed our laboratory's experience and performed PCR on a bank of 159 frozen CSF samples from patients with glioblastoma multiforme and other neurologic disorders. Based on the inability to detect HSV in any other tumor sample, we conclude that the positive HSV PCR in our two index patients most likely represented false-positive results. A diagnosis of HSE should not be made by PCR alone when the clinical presentation is atypical.

Brain Neoplasms↗
PubMed2000

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.

Adult↗
PubMed2000

Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma. NABTT CNS Consortium.

9-Aminocamptothecin (9-AC) was administered as a 72-h i.v. infusion every 2 weeks to a total of 99 adults with high-grade astrocytomas. Fifty-one patients with newly diagnosed glioblastoma multiforme received 9-AC treatment prior to radiation therapy and 48 patients with high-grade astrocytomas were treated at the time of tumor recurrence. Upon entrance into these research protocols, all patients had measurable disease that was evaluated on a monthly basis with volumetric CT or MRI scans. A partial response was defined by > or =50% reduction in the contrast enhancing volume on stable or decreasing doses of glucocorticoids. The study specified that all apparent responders would have central review of their radiologic studies and histopathology. The initial patients treated with 9-AC were also receiving anticonvulsants and were noted to have minimal myelosuppression with this chemotherapy. Thus, 9-AC doses were escalated from the previously reported maximum tolerated dose (MTD) of 850 microg/m2/24 h. We then established new MTDs for patients receiving enzyme-inducing anticonvulsants. We defined these MTDs to be 1,776 microg/m2/24 h for newly diagnosed, previously untreated patients and 1,611 microg/m2/24 h for patients with recurrent disease. Twenty-two patients with newly diagnosed glioblastoma multiforme received 9-AC at doses > or =1,776 microg/m2/24 h. Of these, 18 had evaluable disease on central review, and 0 of 18 (0%) demonstrated a partial or complete response. Twenty-one patients with recurrent high-grade astrocytomas were treated at 1,611 microg/m2/24 h; 20 had evaluable disease and 0 of 20 (0%) had a partial or complete response. Thus, the overall response rate in the 38 evaluable patients treated at the MTD was 0 of 38 (0%). Furthermore, of the 51 evaluable patients who were treated at doses less than the MTD, only one partial response was observed, yielding an overall response rate of 2%. Evidence of drug failure was rapid with tumor progression in one-half of patients after 2 drug cycles. 9-AC lacks evidence of substantial activity in patients with newly diagnosed or recurrent high-grade astrocytomas.

Adult↗
PubMed2000

Societal response to Hurricane Mitch and intra- versus intergenerational equity issues: whose norms should apply?

Late in the 1998 hurricane season, Central America was slammed by a devastating hurricane. Honduras, Nicaragua. El Salvador, Guatemala, and Belize were greatly impacted by Hurricane Mitch, one of the deadliest storms to affect the region in the past 200 years. The economies of each of these countries were badly affected. In the case of Honduras-at the time the fourth-poorest country in Latin America-its president suggested that 50 years of progress had been wiped out by the floods and mudslides associated with this relatively short-lived storm system. Humanitarian assistance poured into the region in the first months following the disaster. As of mid-2000, various national, bilateral, international, and nongovernmental programs were in progress or on the drawing board for recovery, reconstruction, and renewed development of the worst affected countries. Using Honduras as a case study, some of the ethical issues that abound in the decisions of whom to help, when, and how to help them in the wake of such an extreme climate-related human tragedy are examined. Should development assistance be focused on those who have been directly and adversely affected by this storm, or should the emphasis be on reducing the risk of exposure by future generations to such disasters? Is there yet another approach that seeks to protect future generations from similar harm while at the same time assisting present-day victims to get through their hardships?

Journal Article↗
PubMed1998

Histologic evidence of a radiosensitizing effect of Taxol in patients with astrocytomas.

The new anticancer agent Taxol appears to potentiate the effects of radiation on brain tumor cell lines in vitro and was recently evaluated by our group as a radiosensitizer in a phase I study for primary brain tumors. In that study, we administered Taxol as a three-hour IV infusion repeated every week for six weeks and gave daily cranial irradiation concurrently for a total of 6000 rads. We reviewed the charts of the 60 patients who participated in the study, and identified twelve patients who underwent a second surgery after treatment because of progressive symptoms and an enlarging intracranial mass on MRI. Pathologically, each patient showed prominent radionecrosis, and other evidence of accelerated radiation changes (confluent areas of coagulative necrosis, bizarre nuclei, marked thickening and fibrinoid changes in multiple blood vessels). These changes were noted many weeks earlier than would be expected after radiation therapy alone and were independent of age, and tumor histology. We postulate that the accelerated radiation changes may be due to the radiation sensitizing effects of Taxol. We also noted a change of the pattern of tumor recurrence, compared to historic reports, and a dose-necrosis relationship where the resected tumor is formed completely of necrotic tissue in patients who received 150 mg/m2 or higher dose of Taxol. These observations may be of significance for future study design.

Adult↗
PubMed1998

Phase I trial of weekly paclitaxel in advanced lung cancer.

PURPOSE: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose (MTD) of paclitaxel using an extended weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/microL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. RESULTS: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle 1. Neutropenia was dose-limiting. Fourteen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% +/- 10%) patients demonstrated an objective response. CONCLUSION: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

Adult↗
PubMed1996

Concurrent Paclitaxel and Radiation Therapy for Solid Tumors.

BACKGROUND: Combination radiation and chemotherapy has an intuitive appeal for improving cancer treatment. Experimental results suggest that paclitaxel plus radiation might produce additive or synergistic effects. METHODS: A series of phase I and II trials to test tolerance and begin to evaluate effectiveness were performed on patients with non-small cell lung cancer, high-grade astrocytic brain tumors, and pancreatic and gastric cancers. RESULTS: Tolerance of the combined drug and radiation programs was generally good. Esophagitis was dose-limiting for the intrathoracic tumors. Hematologic toxicity was mild, but peripheral neuritis and cutaneous reactions were common. CONCLUSIONS: These trials show that paclitaxel plus concurrent radiation is feasible at the dose levels and schedules tested. Antitumor responses have been observed.

Journal Article↗
PubMed1996

Single-photon emission CT in the evaluation of recurrent brain tumor in patients treated with gamma knife radiosurgery or conventional radiation therapy.

PURPOSE: To differentiate radiation necrosis from tumor recurrence using single-photon emission CT (SPECT). METHODS: Forty-two thallium-201 SPECT scans were obtained in 33 adult patients. All patients had previously been treated with either conventional external-beam radiation therapy (XRT) (26 patients) or gamma knife radiosurgery (16 patients) and had subsequent contrast-enhanced MR examinations before nuclear medicine imaging. Patients were injected intravenously with 4 mCi of thallous chloride Tl 201 with rapid acquisition of SPECT scans thereafter. Findings on thallium-201 SPECT scans were categorized as either positive or negative on the basis of an abnormal focus of increased activity in the area of the known lesion. Evaluation of the accuracy of the thallium-201 SPECT scan was made by correlation with subsequent histologic or cytologic analysis (28 cases) or, in cases in which biopsy was not performed, by subsequent clinical course or MR findings (14 cases). RESULTS: For all patients in this series, the sensitivity and specificity of thallium-201 SPECT scans in detecting tumor recurrence were 94% and 63%, respectively. The sensitivity and specificity for patients who had been treated with XRT were 95% and 60%, respectively. The sensitivity and specificity for patients who had been treated with gamma knife therapy were 92% and 67%, respectively. Tumor/scalp (T/S) ratios were calculated for all patients. High T/S ratios (> 2.0) had a positive predictive value for tumor recurrence of 92%. T/S ratios less than 0.5 had a negative predictive value for tumor recurrence of 83%. CONCLUSION: Thallium-201 SPECT is a sensitive and accurate test to differentiate tumor recurrence from radiation necrosis in a population of patients with abnormal MR findings. This technique was equally efficacious in patients who had undergone gamma knife radiosurgery and in those who had received XRT.

Adult↗
PubMed1996

Preliminary results of a phase I study of weekly paclitaxel infusion in patients with non-small cell lung cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has a broad spectrum of activity, but the optimal schedule has not yet been determined. As a phase-specific agent, more frequent administration theoretically may be more effective. We have previously demonstrated that a weekly schedule of paclitaxel used as a radiation sensitizer is well tolerated by outpatients. We therefore conducted a phase I study of weekly paclitaxel in patients with chemotherapy-naive metastatic non-small cell lung cancer to determine the maximum tolerated dose of this alternative schedule. In all, 26 patients were entered into this study through six paclitaxel dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk) administered weekly for 6 of 8 weeks. All patients had a performance status of 0 through 2, with a median age of 65 years (age range, 37 to 80 years). Sites of disease included lung, bone, liver, soft tissue, and brain. Of the 26 entered, 24 patients completed the first 8-week cycle and are evaluable for toxicity. Dose-limiting toxicity, which consisted of neutropenia, occurred in four of six patients at 200 mg/m2/wk and in two of six at 175 mg/m2/wk. Only one evaluable patient required admission for febrile neutropenia. Other toxicities included rash, pulmonary infiltrate, myalgia, neuropathy, and alopecia. Nine (38%) of the 24 patients demonstrated objective responses. One patient with stable disease completed 48 weeks of therapy. Others remain in active treatment. We conclude that the maximum tolerated dose of paclitaxel administered for 6 consecutive weeks of an 8-week cycle is 175 mg/m2/wk and is limited principally by neutropenia. The response rate with this schedule is encouraging and merits further investigation.

Adult↗
PubMed1995

Vitamin E plus aspirin compared with aspirin alone in patients with transient ischemic attacks.

One hundred patients with transient ischemic attacks, minor strokes, or residual ischemic neurologic deficits were enrolled in a double-blind, randomized study comparing the effects of aspirin plus vitamin E [0.4 g (400 IU)/d; n = 52] with aspirin alone (325 mg; n = 48). The patients received study medication for 2 y or until they reached a termination point. Preliminary results show a significant reduction in the incidence of ischemic events in patients in the vitamin E plus aspirin group compared with patients taking only aspirin. There was no significant difference in the incidence of hemorrhagic stroke although both patients who developed it were taking vitamin E. Platelet adhesion was also measured in a randomized subgroup of both study populations by using collagen III as the adhesive surface. There was a highly significant reduction in platelet adhesiveness in patients who were taking vitamin E plus aspirin compared with those taking aspirin only. Measurement of alpha-tocopherol concentrations confirmed compliance of the patients with the medication schedule, showing a near doubling of serum concentrations of alpha-tocopherol. We concluded that the combination of vitamin E and a platelet antiaggregating agent (eg, aspirin) significantly enhances the efficacy of the preventive treatment regimen in patients with transient ischemic attacks and other ischemic cerebrovascular problems.

Adult↗
PubMed1994

Phase I trial of outpatient weekly paclitaxel and concurrent radiation therapy for advanced non-small-cell lung cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of paclitaxel administered weekly on an outpatient basis with concurrent thoracic radiation to patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In this phase I clinical trial, paclitaxel was administered as a 3-hour intravenous (IV) infusion, repeated every week for 6 weeks. The starting dose of paclitaxel was 10 mg/m2. Doses were escalated at 10-mg/m2 increments in successive cohorts of three new patients if tolerated. Unacceptable toxicity was defined as grade 3 nonhematologic toxicity, excluding nausea and vomiting, and grade 4 hematologic toxicity according to Cancer and Leukemia Group B expanded common toxicity criteria. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). RESULTS: Twenty-seven patients were entered onto this study through seven dose escalations (from 10 mg/m2/wk to 70 mg/m2/wk for 6 weeks). Severe esophagitis occurred at 70 mg/m2 (two patients with grade 4 disease and one patient with grade 2). One of six patients at 60 mg/m2 developed grade 3 esophagitis and three of seven patients had grade 2 esophagitis. One of 27 patients developed a hypersensitivity reaction. One of 27 patients developed grade 3 neutropenia. CONCLUSION: Esophagitis is the principle dose-limiting toxicity of weekly paclitaxel and thoracic radiation in the outpatient setting. A phase II trial using concurrent radiation and paclitaxel at the MTD of 60 mg/m2/wk is underway.

Adult↗
PubMed1992

Preradiation intracarotid cisplatin treatment of newly diagnosed anaplastic gliomas. The CNS Cancer Consortium.

PURPOSE: This phase II study was performed to assess the response of patients with newly diagnosed, untreated malignant gliomas (anaplastic astrocytoma [AA] and glioblastoma multiforme [GBM]) to intracarotid (IC) cisplatin. PATIENTS AND METHODS: Eligibility criteria included surgical intervention limited to biopsy only, measurable contrast-enhancing tumor, and unilateral tumor location within the vascular territory of one internal carotid artery. Patients were scheduled to receive four infusions of IC cisplatin (75 mg/m2 every 4 weeks) before beginning standard radiotherapy. Twenty-six patients were treated, and 22 were assessable for response. RESULTS: Ten patients (45%) showed a greater than 25% decrease in the enhancing tumor area before radiotherapy with stabilization or improvement of neurologic deficits, and three patients (14%) had a greater than 70% decrease in tumor area. The likelihood of response to IC cisplatin was not clearly linked to patient age, tumor histology, or pretreatment tumor size. Myelosuppression, nephrotoxicity, and ototoxicity were mild. Optic neuropathy occurred in one patient, seizures in two, and fatal postinfusion cerebral edema in one. CONCLUSION: This study design, which permits assessment of the drug sensitivity of the untreated glioma, has shown definite antitumor activity of IC cisplatin in newly diagnosed malignant glioma patients.

Adult↗
PubMedDate not supplied

Recurrent primary central nervous system lymphoma complicated by lymphomatous meningitis.

Primary central nervous system lymphomas (PCNSL) are chemosensitive primary brain tumors and are treated primarily with adjuvant chemotherapy. Nonetheless, therapy is palliative with the majority of tumors recurring in brain parenchyma. A common pattern of PCNSL recurrence is that of cerebrospinal fluid (CSF) dissemination manifested as lymphomatous meningitis (LM). Fourteen patients (8 men; 6 women) 34-76 years of age (median 56 years) with recurrent PCNSL manifested as either lymphomatous meningitis (8 patients) or combined parenchymal and CSF disseminated tumor (5) were retrospectively evaluated. All patients had received prior adjuvant therapy including surgery (gross total resection in 3; biopsy in 11), radiotherapy (whole brain in 11; craniospinal in 1; and orbital in 1) and chemotherapy (systemic in 13; intraventricular in 4). At recurrence, documented by either positive CSF cytology (14 patients) or neuroradiographic evidence of disease progression (6 patients), all patients were evaluated for extent of central nervous system disease. Two patients not previously irradiated were treated with whole brain radiotherapy. Eight patients received systemic chemotherapy including 7 patients (Brown University; Group A) treated with either high dose methotrexate (n=4) or cytosine arabinoside (n=3). Seven patients (UCSD: Group B) received intraventricular chemotherapy (methotrexate 5; cytosine arabinoside 4; thio-TEPA 4) without concomitant high dose systemic chemotherapy. Four of 14 patients (28.6%) are disease-free and have durable responses (median 36 months, range 22-56 months). Ten patients (71.4%) have died of disease progression (5 due to combined PCNSL and LM; 4 due to LM; and 1 due to PCNSL). Median survival was 5.5 months with a range of 3-12 months. Grade III/IV myelosuppression was seen in 5 patients, all as a result of systemic chemotherapy (Group A patients). Aseptic meningitis due to intraventricular chemotherapy was seen in 7 patients (Group B patients). No treatment-related deaths occurred. Four patients are disease-free and manifest leukoencephalopathy of whom 2 are symptomatic. Outcome was comparable in Group A and B patients. Recurrent PCNSL complicated by LM may be palliated by combined modality therapy and in this small series, approximately one-quarter of patients (two from each treatment group) are long-term survivors and disease-free. Outcome is similar in patients treated with intraventricular chemotherapy as compared to patients treated with high dose systemic methotrexate or cytosine arabinoside. Treatment-related toxicity was manageable however delayed neurotoxicity is seen in disease-free survivors.

Adult↗