Dramatic response to chemotherapy in oligodendroglial gliomatosis cerebri.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
David Schiff
Publications and source records attributed to David Schiff.
Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study.
PURPOSE: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. PATIENTS AND METHODS: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. RESULTS: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%). CONCLUSION: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).
Adult↗
Neurologic complications of solid tumors.
This article reviews the neurologic complications of the most common solid tumors, including lung, breast, gastrointestinal, genitourinary, gynecologic, head and neck cancers, melanoma and sarcomas. As systemic therapy improves for many of these tumors, patients are surviving longer and the incidence of neurologic complications is increasing.
Brain Neoplasms↗
Spinal cord compression.
Back pain and suspected spinal cord compression remains one of the most frequent reasons for neurologic consultation in cancer patients. While treatment generally results in stabilization or improvement, early diagnosis remains the cornerstone of improving neurologic outcome. This article reviews the clinical features, differential diagnosis, and management of neoplastic epidural spinal cord compression.
Decompression, Surgical↗
The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: a surveillance, epidemiology, and end results analysis.
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL appears to be increasing. METHODS: PCNSL incidence data from 1973-1997 were obtained from the nine Surveillance, Epidemiology and End Results (SEER) registries. To limit the influence of the human immunodeficiency virus on incidence rates, data of never-married males and females and persons of unknown marital status were excluded. As a surrogate for new technology, SEER data were reviewed by dates of diagnosis (surrogate for imaging) and compared with glioma incidence (surrogate for stereotactic neurosurgery and improved diagnostic neuropathology). Age-adjusted incidence rates were estimated and compared for the period prior to computed tomography (CT) (1973-1984) and the magnetic resonance imaging (MRI) period (1985-1997). The estimated annual percent change was calculated based on linear regression analyses using SEER*STAT. RESULTS: The incidence of PCNSL appears to be increasing in all SEER registries examined. All age groups demonstrated an increase over time. This increase was observed both in the CT era as well as in the MRI era. PCNSL age-adjusted incidence (0.15 to 0.48, a 3-fold increase) outpaced that of systemic lymphoma (14.1 to 18.5, a 33% increase) for the same registries over the same time periods. The rate of increase has begun to slow since 1985; the estimated annual percent change for PCNSL was three-fold higher during the period 1973-1985 compared with 1986-1997. CONCLUSION: The incidence rate of PCNSL continues to rise. The increase is evident in all age groups and in both genders. Data from the current study suggest that improved diagnostic tools, such as CT or MRI, cannot explain this increase.
Adult↗
A phase II trial of thymidine and carboplatin for recurrent malignant glioma: a North American Brain Tumor Consortium Study.
This phase II study in recurrent high-grade glioma evaluated the response rate, toxicities, and time to treatment failure of high-dose carboplatin modulated by a 24-h infusion of thymidine (75 g/m(2)). The trial was based on preclinical data and a prior phase I study ( J. Clin. Oncol. 17, 2922-2931, 1999); a phase II recurrent high-grade glioma study was initiated in July of 1998. Thymidine was given over 24 h; carboplatin was given over 20 min at hour 20 of the thymidine infusion. The starting dose of carboplatin had a value of 7 for the area under the curve (AUC), with allowance for dose escalation of 1 AUC unit per cycle if grade 2 toxicity was observed. Treatment cycles were repeated every 4 weeks. Accrual as of September 1999 was 45 patients [4 were unevaluable]: 76% with glioblastoma multiforme (GBM), 20% with anaplastic oligodendroglioma, 2% with mixed type, and 2% with anaplastic astrocytoma. Most patients had prior chemotherapy (78%). As observed in the earlier phase I study (in which carboplatin pharmacokinetics were unaltered by thymidine or antiseizure medications), thymidine was myeloprotective, resulting in a minimal need for dose reduction for patients having a >2 grade toxicity (in only 4% of the courses of treatment). Of 101 total courses, the number of courses (at the AUCs) was 3 (5), 4 (6), 58 (7), 20 (8), 11 (9), and 5 (10). Grade 3 nonhematologic toxicities included headache (4%), altered consciousness (3%), fatigue (1%), and nausea (3%). Responses included 2 partial (1 oligodendroglioma, 1 GBM; 5%); 3 minor (1 anaplastic astrocytoma, 2 GBM; 7.3%); 6 stable disease (14.6%); and 30 progressive disease (73.2%). For GBM patients, median survival was 23 weeks (with a 95% confidence interval of 20 to 50 weeks), and progression-free survival was 8 weeks (with a 95% confidence interval of 7-16 weeks). These results in GBM were comparable to other phase II GBM trials and thus do not represent a therapeutic advance in the treatment of GBM. Taken collectively, however, results are consistent with continued investigation of thymidine in combination with chemotherapeutic agents for high-grade glioma and other malignant diseases. The significant myeloprotection afforded by thymidine may have particular relevance to polychemotherapeutic regimens.
Adult↗
Multi-modality therapy leads to longer survival in primary central nervous system lymphoma patients.
BACKGROUND: Primary central nervous system lymphoma (PCL) is more frequently encountered by neurosurgeons given the increasing incidence among both nonimmunocompromised and immunocompromised patients. The most frequent surgery is stereotactic biopsy. Historically, radiation therapy has been the standard treatment modality for this disease and median survival was in the 15-month range. More recently, multi-modality therapy combining radiation therapy with chemotherapy (systemic, intrathecal, and/or intra-arterial) have resulted in longer survivals. We reviewed survival data for our series of patients treated for PCL over the last decade. METHODS: Thirty-four patients with histologically confirmed PCL were treated at our center. Multivariate Cox regression analysis was performed to determine which factor(s) (age, gender, HIV status, Karnofsky Performance Scale, chemotherapy, single modality therapy, histology, location, number of lesions, surgical resection) had a significant impact on survival. RESULTS: The overall median survival was 19 months. Patients receiving multi-modality therapy (n=17) (chemotherapy and radiation) had a median survival of 34 months compared to four months for patients receiving single modality therapy (n=17 including seven HIV positive patients). Multi-modality therapy was the only significant factor affecting survival in this multivariate analysis (p<0.0001). CONCLUSIONS: Chemotherapy plus radiotherapy significantly enhances survival over patients treated with single modality therapy alone. Quality of life issues should be addressed on a case by case basis as additional treatment modalities are initiated.
Adult↗