ABSTRACT
BACKGROUND: Peripheral neuropathy is a frequent side effect of bortezomib chemotherapy. Relatively little is known about the clinical characteristics of this neuropathy, especially with respect to pain. Our aim was to describe the clinical characteristics and course of bortezomib-induced polyneuropathy. METHODS: This is a retrospective cohort study of 39 patients diagnosed with bortezomib-induced polyneuropathy. RESULTS: Pain is the most prominent symptom and 14 of 39 patients suffered from severe pain. More than 50% of our patients used analgesics due to moderate or severe pain. We found no correlation between severity of symptoms of bortezomib-induced polyneuropathy and cumulative dose or dose intensity of bortezomib. Nerve conduction studies did not correlate well with symptom severity. Dose reduction or discontinuation of treatment reduced severity in most cases. CONCLUSION: Painful polyneuropathy is a frequent, dose-limiting side effect of bortezomib with a relatively good prognosis. Careful neurological monitoring of symptoms and timely dose adjustment is important.
Subject(s)
Boronic Acids , Bortezomib , Antineoplastic Agents/therapeutic use , Boronic Acids/therapeutic use , Cohort Studies , Humans , Multiple Myeloma , Polyneuropathies , Pyrazines/therapeutic use , Retrospective StudiesABSTRACT
BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade astrocytoma and whether these mutations predict outcome to specific treatment. METHODS: We retrospectively investigated the correlation of IDH1 and IDH2 mutations with overall survival and response to temozolomide in a cohort of patients with dedifferentiated low-grade astrocytomas treated with temozolomide at the time of progression after radiotherapy. RESULTS: IDH1 mutations were present in 86% of the 49 progressive astrocytomas. No mutations in IDH2 were found. Presence of IDH1 mutations were early events and significantly improved overall survival (median survival 48 vs 98 months), but did not affect outcome of temozolomide treatment. CONCLUSION: These results indicate that IDH1 mutations identify a subgroup of gliomas with an improved survival, but are unrelated to the temozolomide response.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Astrocytoma , Brain Neoplasms , Dacarbazine/analogs & derivatives , Isocitrate Dehydrogenase/genetics , Mutation/genetics , Adult , Antineoplastic Agents, Alkylating/adverse effects , Astrocytoma/drug therapy , Astrocytoma/genetics , Astrocytoma/mortality , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Cohort Studies , DNA Mutational Analysis , Dacarbazine/adverse effects , Dacarbazine/therapeutic use , Female , Humans , Male , Retrospective Studies , Survival Analysis , Temozolomide , Treatment OutcomeABSTRACT
OBJECTIVE: To describe the results of the treatment of recurrent glioma with temozolomide. DESIGN: Retrospective. METHOD: This study evaluated 77 patients with a recurrent high-grade glioma who from August 1997-December 2003 were treated with temozolomide (150-200 mg/m2/day for 5 days per 28-day cycle) following surgery and radiotherapy at the Daniel den Hoed Oncology Centre of the Erasmus MC, Rotterdam, the Netherlands. The patients were divided into 4 groups depending on histology and chemotherapy history. RESULTS: 15 patients received temozolomide for a recurrent anaplastic oligodendroglioma or mixed oligo-astrocytoma. The response in this group was 80% and after 12 months in 47% of the patients there was no disease progression. 35 patients underwent second-line chemotherapy with temozolomide after earlier chemotherapy with procarbazine, lomustine and vincristine for recurrent anaplastic oligodendroglioma or mixed oligo-astrocytoma. Response was 26% and after 12 months in 15% of patients there was still no disease progression. 14 patients were treated with temozolomide for a recurrent anaplastic astrocytoma with a response of 35% and after 12 months in 8% of these patients there was no disease progression. Of the 13 patients with a recurrent glioblastoma who were treated with temozolomide 16% responded and after 6 and 12 months 21% were still free from progression. Temozolomide was well-tolerated: 2 patients had to stop because of probable side effects. CONCLUSION. Temozolomide has an acceptable safety profile and may be regarded as the preferred treatment for recurrent anaplastic gliomas after radiotherapy. There is only a limited role for temozolomide in the treatment of recurrent glioblastoma.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/drug therapy , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Glioma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Disease Progression , Female , Humans , Male , Middle Aged , Retrospective Studies , Temozolomide , Treatment OutcomeABSTRACT
The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma. The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the region 1p36. Four of the 24 patients responded (17%). Fifty percent of patients were still free from progression at 6 months and 21% were free from progression at 12 months. Although a clear relation existed between loss of 1p and response to temozolomide chemotherapy, this relation was absent in salvage PCV chemotherapy.
