Temozolomide chemotherapy in recurrent oligodendroglioma.

The authors determined the tolerance, response rate, and duration of recurrent anaplastic oligodendroglioma in 30 patients to temozolomide given orally at 150 to 200 mg/m2 on days 1 through 5 in cycles of 28 days. Nine patients responded: 7 of 27 patients (26%) treated with temozolomide after prior PCV chemotherapy and 2 of 3 chemotherapy-naive patients (both complete response). Median time to progression in responding patients was 13 months. Temozolomide shows promise and has an acceptable safety profile in recurrent anaplastic oligodendroglial tumors. Patients not responding to PCV may respond to temozolomide.

Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients.

We reviewed 200 patients with paraneoplastic encephalomyelitis (PEM) and anti-Hu antibodies to show possible clinical differences with respect to previous series, and to identify patient, tumour and treatment-related characteristics associated with neurological disability and survival. The median age of the 200 patients was 63 years (range 28-82 years) and 75% were men. The predominant neurological syndromes were sensory neuropathy (54%), cerebellar ataxia (10%), limbic encephalitis (9%) and multifocal involvement (11%). Sensorimotor neuropathies with predominant motor involvement were observed in only 4% of the patients. Pathological or X-ray evidence of a tumour was obtained in 167 patients (83%) and was a small-cell lung cancer (SCLC) in 74% of those with histological diagnosis. Coexistence of extrathoracic tumours with SCLC was rare (0.5%). Positive Hu immunoreactivity was observed in the extrathoracic tumours of six out of seven patients in whom autopsy or long-term follow-up ruled out a coexisting SCLC. PEM preceded the diagnosis of the tumour in 71% of patients (mean delay +/- SD 6.5 +/- 7.0 months; range 0.1-47 months). In the 24 patients in whom the tumour diagnosis was the initial event, PEM predicted the progression or relapse of the tumour in 87% of them. No tumour was found in 33 patients, including four who had a post-mortem study and four with >5 years of follow-up. In a logistic regression analysis, treatment of the tumour, associated or not with immunotherapy, was an independent predictor of improvement/stabilization of PEM [odds ratio 4.56; 95% confidence interval (CI) 1.62-12.86]. Cox multivariate analysis indicated that the variables independently associated with mortality were: age >60 years [relative risk (RR) 1.49; 95% CI 1.05-2.12], Rankin score at diagnosis >3 (RR 1.60; 95% CI 1.12-2.28), more than one area of the nervous system affected (RR 1.61; 95% CI 1.08-2.40), and absence of treatment (RR 2.56; 95% CI 1.76-3.71). We conclude that, unlike previous series, the majority of our patients were male, and there was a low occurrence of predominantly motor neuropathies and extrathoracic tumours coexisting with SCLC. When the diagnosed extrathoracic tumour expresses Hu antigens, further tests to rule out a coexisting SCLC are probably unnecessary. Finally, the predictors of mortality and PEM evolution found in the study may be important in the design of future therapeutic protocols, and emphasize the importance of early diagnosis and treatment of the underlying tumour.

Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies.

The outcome of 34 women with anti-Yo-associated paraneoplastic cerebellar degeneration was reviewed. Three patients had not developed cancer after more than 4 years of follow-up. The only independent predictor for survival was the type of associated tumor (risk ratio, 1.79; 95% CI, 1.02 to 3.12). Median survival was 100 months for patients with breast cancer and 22 for those with gynecologic cancer. Although paraneoplastic cerebellar degeneration leads to the diagnosis of cancer in 63% of the patients, cancer progression was the cause of death in 52%.

Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone.

OBJECTIVES: To evaluate the effect of a combination of immunoglobulins (IVIg), cyclophosphamide (CTX), and methylprednisolone (MP) on the clinical course of patients with paraneoplastic neurological syndrome (PNS) and antineuronal antibodies (Abs). METHODS: Seventeen patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) with anti-Hu Abs (n = 10) or cerebellar degeneration (PCD) with anti-Yo Abs (n = 7) received one to nine cycles (mean 3.5) of a combination of IVIg (0.5 g/kg/day from days 1 to 5), CTX (600 mg/m2 at day 1) and MP (1g/day from day 1 to 3). The Rankin scale (RS) was used to evaluate the response. A positive response was considered as either improvement or stabilisation in patients who were still ambulatory (RS< or =3) at the onset of treatment, whereas only improvement, and not stabilisation, was considered a therapeutic benefit in bedridden patients (RS> or =4). RESULTS: Tolerance was good and no patient experienced grade 3/4 toxicity (World Health Organisation). Sixteen patients were evaluable for response. Of the seven patients with RS> or =4, none improved. Of the nine patients with RS< or =3, none improved but three (two SN and one PCD) stabilised for 4, 35, and 16 months. CONCLUSIONS: This study suggests that vigorous immunosuppressive treatment is not useful in severely disabled PNS patients with antineuronal Abs. In a minority of patients (mainly with SN) who are not severely disabled at the onset of treatment, a transient stabilisation is possible and deserves further evaluation.

Second line chemotherapy with docetaxel in patients with recurrent malignant glioma: a phase II study.

The objective of the study was to assess the efficacy of docetaxel in recurrent supratentorial malignant gliomas. The sample size of the study was determined by the Gehan's method for a response rate of 20% and a beta error of 5%. In the first step 14 patients (age 27-69, median 50; Karnofsky index 50-90, median 75) with recurrent malignant glioma after surgery, radiotherapy and nitrosourea, were enrolled (12 glioblastomas, 2 anaplastic astrocytomas). Docetaxel at the initial dose of 80 mg/m2 was administered every 3 weeks until progression or unacceptable toxicity. A total of 41 cycles was administered. Patients received a median of two cycles (range 1-6). No complete or partial response was observed. Therefore, according to the design of the study, no additional patients were enrolled and the trial was terminated. Two stabilizations were observed (14 and 15 weeks). Median TTP was 7 weeks (44 days). Median overall survival from recurrence was 26.5 weeks (6.4 months). Grade 3-4 neutropenia was observed in 8 patients (57%) but no life-threatening toxicity was observed. Other toxicities were uncommon and mild. Dose reduction was performed in 5 patients. This study suggests that docetaxel displayed no significant activity in patients with malignant recurrent gliomas.

Clinical outcome of patients with anti-Hu-associated encephalomyelitis after treatment of the tumor.

OBJECTIVE: To evaluate 1) the effect of the tumor treatment on the clinical course of paraneoplastic encephalomyelitis (PEM) with anti-Hu antibodies, 2) the impact of immunotherapy on the tumor evolution, and 3) the outcome of the small cell lung cancer (SCLC) of PEM patients compared with that of patients without PEM. METHODS: The authors retrospectively analyzed 51 PEM patients (42 with SCLC, 9 with other tumors) who received antineoplastic treatment with (25 patients) or without (26) concomitant immunotherapy. Tumor response was assessed at the end of the antineoplastic treatment. Progression of PEM was defined as a change of at least 1 point in the Rankin scale measured at the onset and at the end of the tumor treatment. To evaluate the outcome of SCLC, 27 PEM patients with SCLC were matched one-to-one with SCLC patients without PEM for age, performance status, tumor stage, and type of antineoplastic treatment. RESULTS: Thirty-six (70%) patients were neurologically stable at the end of the tumor treatment. In a logistic regression analysis, tumor complete response was the only predictor of PEM stabilization (OR 7.07; 95% CI 1.68 to 29.76; p = 0.006). Immunotherapy did not modify the outcome of the tumor and PEM. Median survival was similar in SCLC patients with and without PEM, but the probability of survival at 30 months was higher in PEM patients with SCLC (OR 5.26; 95% CI 1.0004 to 27.6902; p = 0.03). CONCLUSIONS: Complete response of the tumor seems to have a favorable influence on the course of paraneoplastic encephalomyelitis (PEM). Concomitant immunotherapy does not adversely affect the tumor outcome. The small cell lung cancer of PEM patients may have a slightly better evolution than that of patients without PEM.

Treatment of supratentorial glioblastoma multiforme with radiotherapy and a combination of BCNU and tamoxifen: a phase II study.

From May 1990 to November 1994, 70 consecutive patients suffering from glioblastoma multiforme were treated following surgery with conventional radiotherapy and adjuvant IV BCNU administered alone or in combination with tamoxifen. Twenty-five patients received BCNU alone (control group A) while 24 patients also received 40 mg of tamoxifen (TMX) PO daily (group B) and 21 received 100 mg of TMX PO daily (group C). There were no significant differences between the 3 groups concerning age, type of resection and median post-operative Karnofsky performance status (KPS). Blood toxicity over grade II occurred in 33.5% of patients receiving TMX versus 12% of patients treated with BCNU alone (p < 0.05). Deep venous thrombosis complications were observed in 4 patients of each TMX group, whereas they were not observed in the control group (p < 0.04). Median time to tumor progression (MTTP) was 35 weeks in the control group and 27 weeks in both TMX groups B and C. Median survival time (MST) was 56, 66 and 51 weeks, respectively. These results suggest that the addition of TMX to standard treatment of glioblastomas does not affect the time to tumor progression and overall survival but may increase the risk of deep venous thrombosis or nitrosourea-induced blood toxicity.

Neurological complications of radiotherapy and chemotherapy.

Neurological complications of radiotherapy and chemotherapy can affect the central or peripheral nervous system. Most are dose-dependent and constitute a limiting factor in the administration of treatments. Radiation-induced neurological complications are classified as acute, early-delayed or delayed. The most important are radionecrosis and cognitive dysfunction/leukoencephalopathy. Neurotoxicity of chemotherapy is frequent and depends upon dose, type of drugs (especially cisplatin and methotrexate) and their combination with radiotherapy.