Kendra Peterson

Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing.

Background. Paclitaxel-induced peripheral neuropathy (PN) may be severeand dose-limiting at initial doses ≥ 275 mg/M2, but itsneurotoxicity at doses ≤ 250 mg/M2 has been incompletelycharacterized. The purposes of this study were to characterize and quantifypaclitaxel-induced PN and to determine the utility of quantitative sensorytesting (QST). Methods. We prospectively examined clinically and by QST 37women with metastatic breast cancer, treated with paclitaxel (200–250mg/m2) (average number of cycles = 7.3 over an average of 20.1weeks). QST included thermal threshold (TT) and vibration threshold (VT).Results. Paresthesias appeared in 31 (84%) patients after an averageof 1.7 cycles and an average cumulative dose of 371.5 mg/M2. Symptomsoccurred after the first or second dose in 26 (84%) patients and thenstabilized in 10 (32%), improved in 13 (42%) despite continuedtreatment, resolved completely in 6 (19%), and were progressive in 2(7%). Paclitaxel was discontinued in only 1 (3%) patientbecause of neurotoxicity and no patient required dose reduction because ofPN. Thirty-six (97%) developed signs of PN. The most sensitive QSTwas great toe VT but QST did not predict or identify subclinical PN in anypatient. Neurologic syndromes other than PN developed in 12 (32%)patients, and 7 were due to metastatic cancer. Conclusions. 1)Paclitaxel-induced PN is mostly sensory, and begins after the first orsecond dose. At these doses the neuropathy is mild, and rarelydose-limiting. 2) QST quantified the neuropathy but was less sensitive thanthe clinical examination. 3) Knowledge of the features of paclitaxels PNallows it to be differentiated from other neurologic syndromes which maysignal tumor progression.

Medulloblastoma/Primitive Neuroectodermal Tumor in 45 Adults

Article abstract-Medulloblastoma/primitive neuroectodermal tumor (PNET) is an uncommon tumor in adults. We reviewed the medical records of 45 patients, 15 years or older, with medulloblastoma/PNET. Most patients presented with symptoms referable to the posterior fossa, and 31 of 45 patients had disease limited to the posterior fossa at the time of diagnosis. Despite initial favorable response to surgical resection, radiation, and chemotherapy, one-half had recurrence 10 to 76 months after initial treatment. Only two of these patients had local recurrence; the remainder had CNS dissemination, systemic metastasis, or both. The recommended approach to medulloblastoma/PNET in adults is similar to that in children, and includes initial staging evaluation, systemic and focal therapy (ie, neuraxis irradiation with posterior fossa boost and chemotherapy), and long-term follow-up to detect late and distant recurrence. NEUROLOGY 1995;45: 440-442

Myeloablative chemotherapy for recurrent aggressive oligodendroglioma

The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving aggressively at recurrence were eligible for this study. Only complete responders or major partial responders (75 % reduction in tumor size) to induction chemotherapy--either intensive-dose procarbazine, lomustine, and vincristine or cisplatin plus etoposide-could receive high-dose thiotepa (300 mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone marrow or peripheral blood stem cells. Thirty-eight patients began induction chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky score 80) received high-dose thiotepa. For the high-dose group, the median event-free, progression-free, and overall survival times from recurrence were 17, 20, and 49 months, respectively. Tumor control in excess of 2 years was observed in 6 patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months (median, 42 months) from the start of induction therapy; however, fatal treatment-related toxicities also occurred in 4 patients (20%). Three patients died as a result of a progressive encephalopathy which, in 2 instances, was accompanied by a wasting syndrome; 1 patient died as a consequence of an intracerebral (intratumoral) hemorrhage. Fatal toxicities occurred in patients with pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate response was a disappointing treatment strategy for patients with recurrent aggressive oligodendroglial neoplasms, although several patients had durable responses. Moreover, as prescribed, high-dose thiotepa had significant toxic effects in previously irradiated patients, especially those with poorer performance status.

High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: Long-term follow-up

We previously reported a phase 2 trial of 69 patients with newly diagnosed anaplastic or aggressive oligodendroglioma who were treated with intensive procarbazine, CCNU (lomustine), and vincristine (PCV) followed by high-dose thiotepa with autologous stem cell rescue. This report summarizes the long-term follow-up of the cohort of 39 patients who received high-dose thiotepa with autologous stem cell support. Thirty-nine patients with a median age of 43 (range, 18-67) and a median KPS of 100 (range, 70-100) were treated. Surviving patients now have a median follow-up of 80.5 months (range, 44-142). The median progression-free survival is 78 months, and median overall survival has not been reached. Eighteen patients (46%) have relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with risk of relapse. Persistent nonenhancing tumor at transplant was identified in our initial report as a significant risk factor for relapse; however, long-term follow-up has not confirmed this finding. Long-term neurotoxicity has developed only in those patients whose disease relapsed and required additional therapy; no patient in continuous remission has developed a delayed neurologic injury. This treatment strategy affords long-term disease control to a subset of patients with newly diagnosed anaplastic oligodendroglioma without evidence of delayed neurotoxicity or myelodysplasia.

Daily low-dose carboplatin as a radiation sensitizer for newly diagnosed malignant glioma

Surgical resection followed by local field radiotherapy is currently our most effective approach to treatment for most patients with malignant glioma. Carboplatin chemotherapy has direct cytotoxic effects on glioma cells and acts as a radiation sensitizer to enhance cell killing. Its demonstrated efficacy as a sensitizer in other solid tumors led to this clinical trial of carboplatin as a radiation sensitizer in the treatment of newly diagnosed glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). Fourteen patients (nine GBM and five AA) were treated with daily low-dose carboplatin 25 mg/m2 intravenously within 2 h of their fractionated radiotherapy to a total dose of 600 mg/m2. No significant toxicities attributable to this combined therapy were observed. All patients have progressed, with median time to progression of 16 weeks. Eleven patients have died, with median survival of 38 weeks for the entire cohort. Although this regimen appeared safe, there was no benefit in survival time compared to historical patients treated with radiotherapy. The limitations and future potential for the strategy of radiation sensitization are discussed.

High-dose Chemotherapy with Stem Cell Rescue as Initial Therapy for Anaplastic Oligodendroglioma

AbstractPurpose: Anaplastic oligodendroglioma is a chemosensitive glial neoplasm. To improve disease control and postpone cranial radiotherapy, we designed a phase II study of intensive procarbazine, lomunstine and vincristine followed by high-dose thiotepa with autologous stem cell rescue for patients with newly diagnosed anaplastic or aggressive oligodendroglioma. Patients and methods: Sixty-nine patients with a median age of 42 (range: 18–67) and a median Karnofsky Performance Score of 90 (range: 70–100) were enrolled. Sixteen patients had a prior diagnosis of low-grade oligodendroglioma and 16 had mixed oligoastrocytoma pathology. Only patients with demonstrably chemosensitive enhancing tumors or those free of enhancing tumor after surgery and induction therapy were eligible to receive high-dose thiotepa. Results: Thirty-nine patients (57%) completed the transplant regimen; their estimated median progression-free survival is 69 months and median overall survival has not been reached. Twelve transplanted patients (31%) relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with relapse; however, persistent non-enhancing tumor at transplant conferred an increased risk of relapse (p = 0.028). The transplant regimen was well-tolerated; median hospital stay was 20 days (range: 7–43) with a median time to ANC and platelet engraftment of 10 days. Thirty patients (43%) did not receive high-dose thiotepa because of stable or progressive disease (n = 21), excessive toxicity (n = 4), refusal of further therapy (n = 2), failure to obtain insurance coverage (n = 2), or other (n = 1). No treatment-related or long-term neurotoxicity was seen in the transplanted patients. Conclusions: High-dose chemotherapy with stem cell rescue as initial treatment for anaplastic oligodendroglioma is feasible and associated with prolonged tumor control in some patients.

Post-irradiation polyradiculopathy mimics leptomeningeal tumor on MRI

Three patients with a remote history of Hodgkin’s disease treated with total or subtotal lymphoid radiation 17 to 24 years earlier developed lumbosacral polyradiculopathy associated with nodular meningeal enhancement of the conus medullaris and cauda equina on MRI. None had evidence of recurrent Hodgkin’s disease or second malignancy, and the MRI findings may be sequelae of radiation therapy.

Weighing the benefits and risks of radiation therapy for low-grade glioma

Radiotherapy is the most effective nonsurgical treatment for gliomas. Its role in the treatment of malignant gliomas is well defined, but its efficacy and optimal timing of administration for low-grade gliomas is less clear. Most patients with low-grade glioma are adults in their 20s or 30s who present with seizures and have a nonenhancing mass on neuroimaging. The majority of these patients are neurologically intact and their seizures are easily controlled with anticonvulsants. Typically, radiotherapy was employed immediately to control disease and delay malignant progression. However, in the past 10 to 20 years it has become increasingly apparent that radiotherapy may be associated with long-term cognitive dysfunction. Furthermore, its true benefit and its long-term cognitive risks have been difficult to establish. There is now a growing body of evidence that suggests that deferring radiotherapy in patients with low-grade glioma has no deleterious effects on …

Salvage chemotherapy for oligodendroglioma

The authors present their experience with salvage chemotherapy for oligodendroglioma, an uncommon brain tumor that responds predictably to PCV (procarbazine, lomustine (CCNU), and vincristine) when given as initial therapy. The authors reviewed the records of patients with oligodendrogliomas who received a second, third, or fourth cytotoxic regimen prescribed to combat tumor recurrence documented by computerized tomography or magnetic resonance imaging following an initial chemotherapy program. Initial regimens were prescribed at various time points: as neoadjuvant therapy prior to radiotherapy, as adjuvant therapy in conjunction with radiotherapy, or at recurrence following radiotherapy. Response criteria were based on measurable changes in tumor size following published guidelines. Twenty-three patients (14 men and nine women) aged 25 to 58 years (median 36 years) received 33 salvage regimens. When non-PCV chemotherapy had been the prior regimen, seven (88%) of eight patients responded to salvage chemotherapy, all seven (100%) responding to PCV. Administration of PCV was effective after regimens of carmustine and CCNU but was ineffective after prior administration of PCV. When PCV had been given any time previously, only four (19%) of 21 patients responded to salvage chemotherapy; however, four (40%) of 10 patients who received etoposide (VP-16)/cisplatin (CDDP) responded. Despite the small number of patients, two noteworthy trends emerge from these data: first, PCV is a highly effective salvage treatment when used at tumor recurrence following non-PCV chemotherapy regimens, and second, the synergistic combination of VP-16 and CDDP may exert substantial anti-oligodendroglioma activity, and it warrants further evaluation.