Mary Welch

Autologous stem cell transplant in recurrent or refractory primary or secondary central nervous system lymphoma using thiotepa, busulfan and cyclophosphamide

Abstract The prognosis for patients with central nervous system (CNS) involvement by recurrent or refractory diffuse large B-cell lymphoma is poor, with overall survival (OS) of 4–10 months. High-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) is a potential treatment alternative. We reviewed patients with recurrent primary (PCNSL) or secondary (SCNSL) CNS lymphoma referred for consolidation HDC-ASCT utilizing thiotepa, busulfan and cyclophosphamide (TBC). Among the 17 patients included, all had achieved a complete remission after salvage induction chemotherapy, which incorporated methotrexate in 82% of patients. Two patients failed stem-cell harvesting and 15 (88%) underwent transplant. The estimated 3-year progression-free survival (PFS) and OS were both 93% (95% confidence interval 61–99%). Median PFS and OS were not reached. There was no transplant-related mortality. These results confirm the benefit of TBC followed by ASCT in select patients with recurrent PCNSL and suggest a potential role for the regimen in those with SCNSL. Further investigation is warranted.

Retrospective analysis of the effects of steroid therapy and antidiabetic medication on survival in diabetic glioblastoma patients

AIMS Type 2 diabetes mellitus (DM2) affects 10% of the population, but little is known about how DM2 and antidiabetic medication impact glioblastoma (GBM) patients. PATIENTS & METHODS We retrospectively reviewed GBM patients with DM2 seen at a single institution from 1998 to 2010. RESULTS Of 988 GBMs, 124 (12.6%) were affected by DM2. Thirty-four developed DM2 after steroid use and 89 had pre-existing DM2. Median overall survival among diabetic GBMs was 10 months compared with 13 months among nondiabetics. Only 15% of diabetic patients achieved sustained steroid taper. Sixty-seven (54%) were managed with a single antidiabetic medication and, within this monotherapy group, Karnofsky Performance Score, resection status, steroid dependency and metformin use were the most important predictors of survival on multivariate analysis. CONCLUSION The prevalence of DM2 among GBMs is similar to that of the general population. A more aggressive approach to steroid tapering and the choice of antidiabetic drug may improve survival within this patient population.

Phase I trial of sequential raltitrexed followed by bolus 5-fluorouracil in patients with advanced colorectal cancer

Our objective was to determine the maximum tolerated dose (MTD) of sequential raltitrexed (Tomudex) and 5-fluorouracil (5-FU) by bolus administration every 3 weeks in patients with advanced colorectal cancer (aCRC) and appendiceal adenocarcinoma. This phase I dose-escalation study was carried out in three stages: (1) 5-FU fixed at 900 mg/m2, raltitrexed escalated from 0.5 to 3.0 mg/m2, (2) raltitrexed fixed at 3.0 mg/m2, 5-FU escalated from 900 mg/m2 until dose-limiting toxicity (DLT) and (3) 5-FU fixed at the dose level below DLT, raltitrexed escalated from 3.0 mg/m2 until MTD. Seventy-one patients with measurable disease were enrolled. No DLTs were observed during stage 1 of treatment. At a fixed dose of raltitrexed 3.0 mg/m2, DLT developed when 5-FU was increased to 1350 mg/m2 (stage 2). When 5-FU was fixed at 1200 mg/m2 and raltitrexed was increased to 6.0 mg/m2 (stage 3), DLT was dose limiting. The recommended doses for further study are 5.5 mg/m2 ralitrexed and 1200 mg/m2 5-FU. Of the 69 patients evaluated for efficacy, one had a complete response (8.0 months) and five had partial responses (5.1–11.6 months). Thirty patients had stable disease for 5 or more cycles of therapy (mean time to progression: 3.6 months). Median survival was 11.7 months. We conclude that raltitrexed can be combined with bolus 5-FU, at raltitrexed doses that are higher than the recommended single-agent dose of 3.0 mg/m2, with manageable toxicity. This combination shows encouraging activity, and survival appears promising in the pre-treated aCRC patient population. Further clinical trials are warranted.

Headaches in Patients with Pituitary Tumors: a Clinical Conundrum

Purpose of ReviewPituitary tumors account for approximately 17% of all intracranial neoplasms, with the majority being pituitary adenomas. Often, these are found incidentally during a workup for headache; however, the relationship between symptom and pathology remains unclear. The purpose of this article is to review the most recent literature on the epidemiology, pathophysiology, and management of headaches in patients with pituitary tumors.Recent FindingsThe current literature is limited, with few prospective trials focusing on this question. With the exception of pituitary apoplexy, the relationship between headaches and pituitary masses remains unclear. Intervention does not always improve headache and can lead to development of new headache syndromes.SummaryFurther research is needed to better elucidate the relationship between pituitary tumors and headaches. Headache alone is rarely an indication for surgical management of a pituitary adenoma.