Survival of adults treated for medulloblastoma using paediatric protocols

We retrospectively studied 26 consecutive adults treated for medulloblastoma using paediatric protocols. Between 1987 and 2003, patients 18 years old were given adjuvant chemotherapy consisting of one of two 'paediatric' regimens (depending on the time of presentation) and craniospinal local-boost radiotherapy: regimen A (n = 12), vincristine (VCR), intrathecal and/or intravenous methotrexate and conventional radiotherapy; or regimen B (n = 11) sequencing intensive doses of multiple agents followed by hyperfractionated accelerated radiotherapy (HART). A VCR-lomustine-based maintenance followed both regimens. Three additional patients received a tailored treatment due to their impaired neurological status after surgery. The median age at diagnosis was 26 years (range 18-41 years). With a median follow-up of 46 months, 5-year disease-free and overall survival rates were 65+/-11% and 73+/-10%, respectively, for the series as a whole. All patients who received regimen B (5 of whom had metastatic Chang M2-M3 disease) are alive with no evidence of disease at 39 months. Although the number of patients is limited, our data suggest that the sandwich sequential, moderately intensive chemotherapy in combination with HART is an effective treatment for medulloblastoma in adults, and this approach seems to overcome previously-recognised risk factors.     

Sequential antibodies to potassium channels and glutamic acid decarboxylase in neuromyotonia

A patient with thymoma-associated neuromyotonia and voltage-gated potassium channel (Kv1.2 and Kv1.6) antibodies by immunoprecipitation and rat brain immunolabeling was treated successfully with immunoadsorption and cyclophosphamide. Curiously, glutamic acid decarboxylase antibodies, absent at onset, appeared later. Stiff-person syndrome was absent, but fast blink reflex recovery suggested enhanced brainstem excitability. The range of antibodies produced in thymoma-associated neuromyotonia is richer, and the timing of antibody appearance more complex, than previously suspected.     

Efficacy and tolerability of gefitinib in pretreated elderly patients with advanced non-small-cell lung cancer (NSCLC)

The activity and toxicity profile of gefitinib in non-small cell lung cancer (NSCLC) patients aged 70 years or older has been only partially evaluated. The aim of this study was to evaluate the response rate and safety of gefitinib in elderly NSCLC patients. Elderly NSCLC patients pretreated with chemotherapy and with at least one measurable lesion received gefitinib at the daily dose of 250 mg until disease progression, unacceptable toxicity or refusal. From August 2001 to May 2003, 40 consecutive elderly patients have been enrolled onto the study in three Italian institutions. We observed one complete (2.5%) and one partial response (2.5%), 18 disease stabilisations (NC: 45%) lasting at least 2 months, including six patients (15%) who had disease stabilisation of 6 months or longer, for an overall disease control rate of 50% (95% CI: 34.5-65.5%). The median duration of response was 4.4 months (range 1.7-9.2). The side effects were generally mild and consisted of diarrhoea and skin toxicity. Grade 1-2 diarrhoea occurred in 23.6%, and one patient experienced grade 4 diarrhoea, requiring hospitalisation. Grade 1-2 skin toxicity, including rash, pruritus, dry skin, and acne, occurred in 20 patients (52.6%). Gefitinib is safe and well tolerated in elderly pretreated NSCLC patients. The disease-control rate achieved suggests that this drug could represent a valid option in the management of this unfavourable subgroup of patients.     

Imatinib mesylate in chordoma

BACKGROUND: To the authors' knowledge, no effective medical therapy currently is available for advanced chordoma. Imatinib mesylate is a tyrosine kinase inhibitor targeting platelet-derived growth factor receptor-beta (PDGFRB), BCR-ABL, and KIT. METHODS: Six patients with advanced chordoma were treated with imatinib mesylate at a dose of 800 mg daily. In all patients, the tumor was found to be positive for PDGFRB, and in four patients PDGFRB was shown to be phosphorylated/expressed. RESULTS: After a treatment period of > or = 1 year, overt tumor liquefaction was evident on computed tomography (CT) scan in the first patient. In previous months, a decrease in contrast enhancement on magnetic resonance imaging (MRI) and a decrease in glucose uptake on positron emission tomography (PET) were detected. Similar signs on MRI and PET were observed in subsequent patients, who had a shorter treatment period. One of these patients initially was removed from therapy and then was readmitted to therapy because of difficulties with regard to tumor response assessment; 1 month after the reinitiation of therapy, an overt decrease in tumor density was visible on CT scan in this patient. In four of five symptomatic patients, a subjective improvement was observed early in the course of treatment. The first patient died after 17 months, with a sizeable, mostly liquefied mass. Another patient died early, apparently of unrelated causes. The remaining patients were on therapy at the time of last follow-up. CONCLUSIONS: Imatinib mesylate has been found to have antitumor activity in patients with chordoma. This activity might be mediated by inactivation of PDGFRB. Tumor response manifests through patterns that are similar to those observed in patients with gastrointestinal stromal tumors who respond to molecular-targeted therapy, but evolves more slowly. The benefit to the patient entailed by this pattern of tumor response in chordoma needs to be elucidated, but may be limited in the presence of significant local disease.     

A novel intraarterial chemotherapy using paclitaxel in albumin nanoparticles to treat advanced squamous cell carcinoma of the tongue: preliminary findings

OBJECTIVE: The purpose of our study was to evaluate the effectiveness of intraarterial infusion of paclitaxel incorporated into human albumin nanoparticles for use as induction chemotherapy before definitive treatment of advanced squamous cell carcinoma of the tongue. SUBJECTS AND METHODS: Twenty-three previously untreated patients (age range, 27-75 years) who had carcinoma of the tongue (stage T3-T4, any N) received intraarterial therapy with paclitaxel incorporated into albumin nanoparticles delivered by transfemoral catheterization into the external carotid artery (10 patients), selectively into the lingual artery (12 patients), or into a faciolingual trunk (1 patient). Each patient received two to four infusions, with a 3-week interval between infusions. The dose administered was 230 mg/m(2) in eight patients, 180 mg/m(2) in six patients, and 150 mg/m(2) in nine patients. Sixteen patients underwent surgery. Of these 16 patients, eight subsequently received radiotherapy, and three received a combination of chemotherapy and radiotherapy. Of the remaining seven patients, one received chemotherapy alone, four received radiotherapy alone, one received chemotherapy plus radiotherapy, and one refused any further treatment. RESULTS: Sixty-seven infusions were performed successfully. Eighteen patients (78%) had a clinical and radiologic objective response (complete, 26%; partial, 52%). Three patients (13%) showed stable disease, and two (9%) showed disease progression. The four patients with complete clinical response who underwent surgery showed microscopic residual carcinoma measuring less than 1 mm in two patients, less than 5 mm in one patient, and less than 1 cm in one patient. The toxicities encountered were hematologic (grade 3) in two patients (8.6%) and neurologic (grade 4) in two patients (reversible paralysis of the facial nerve, 8.6%). Two catheter-related complications occurred: one reversible brachiofacial paralysis and one asymptomatic occlusion of the external carotid artery. CONCLUSION: Intraarterial infusion of paclitaxel in albumin nanoparticles proved reproducible and effective and deserves further investigation as induction chemotherapy before definitive treatment of advanced tumors of the tongue, with a view to organ preservation.     

Childhood malignant ovarian germ cell tumors: a monoinstitutional experience

OBJECTIVES: We reviewed our 23-year monoinstitutional exprience with childhood malignant ovarian germ cell tumors (MOGCT), with respect to survival and iatrogenic sequelae. METHODS: Twenty-nine patients (median age 12 years) with newly diagnosed MOGCT were treated: all girls but 2 underwent surgery as initial treatment. There were 9 pure dysgerminomas and 20 nondysgerminoma tumors (5 immature teratomas, 4 yolk sac tumors, and 11 mixed histology tumors). According to the FIGO classification, 9 girls were classified as stage I, 4 as II, 11 as III, and 3 as IV, and 2 were not evaluable because they were submitted to primary chemotherapy. Twenty-four received chemotherapy with VAC, PVB, or PEB regimens, according to the ongoing protocols through the years. Three stage I girls did not receive adjuvant chemotherapy because of their histology (2 dysgerminomas, 1 immature teratoma) and stage. In the early years, postoperative radiotherapy was given alone in advanced dysgerminoma stages. RESULTS: Five patients died of their disease: 2 dysgerminomas (stage IIIc and IV) and 3 nondysgerminomas (2 stage II and 1 stage IIIc). OS and EFS rates at a median of 112 months were 81.8%. Among 24 survivors, 4 experienced iatrogenic amenorrhea because of radiotherapy and/or bilateral oophorectomy. CONCLUSIONS: MOGCT are highly chemosensitive and curable, with preservation of reproductive function. The management of recurrent disease remains an open issue.