Macrocystic and macrohemorrhagic adenomas and solid tumors with enhanced diffusivity are more likely to be successfully managed with transsphenoidal hypophysectomy. Transsphenoidal hypophysectomy of solid, enhancing tumors with restricted diffusion is more likely to fail, possibly because of the greater reticulin content of the tumor; initial transcranial surgery may be appropriate in these cases.
Based on in vitro studies that have demonstrated synergy between recombinant alfa-2a-interferon (rIFN alpha-2a) and the fluoropyrimidine, fluorouracil (5FU), against two human colon cancer cell lines, a pilot clinical trial was initiated to determine the effects of the combination of 5FU and rIFN alpha-2a in patients with advanced, unresectable colorectal carcinoma. A total of 30 patients were enrolled; all were evaluable. 5FU was administered as a loading course, 750 mg/m2 daily for 5 days by continuous infusion followed by weekly bolus therapy, rIFN alpha-2a, 9 MU, was administered subcutaneously three times per week. Of 17 previously untreated patients evaluable for response, 13 achieved a response. Three patients had disease progression. No previously treated patients had a major response. There was one death clearly related to therapy, an event preceded by watery diarrhea and neutropenic sepsis. Other toxicities were reversible and responded to dose reduction. With a median follow-up of 16+ months, median survival has not been reached among the previously untreated patient cohort. We conclude that the combination of 5FU and rIFN alpha-2a is an active regimen against disseminated colorectal cancer in previously untreated patients.
BACKGROUNDA Phase I/II study was designed to show whether the addition of semisynthetic homoharringtonine (sHHT) would reduce the level of residual disease in patients with Ph‐positive chronic myeloid leukemia who appeared to have achieved a suboptimal response to imatinib alone.METHODSPatients with CML who had achieved ≥ 35% Ph‐negativity on imatinib were included. All patients had been treated with imatinib at ≥ 400 mg/day for at least 2 years and had achieved a plateau in BCR‐ABL transcripts defined by measuring BCR‐ABL transcripts on at least 4 occasions over a minimum period of 1 year with the latest value not lower than the previous minimum value. Initially sHHT was given subcutaneously at a dose of 1.25 mg/m2 twice daily for 1 day. Courses were repeated every 28 days. The dosage of sHHT was escalated by adding one day of treatment every two days. Efficacy was assessed by serial monitoring of blood levels of BCR‐ABL transcripts.RESULTSOf 10 evaluable patients, 7 had an appreciable decline in BCR‐ABL transcript levels; in 5 cases the reduction was greater than 1 log. Asthenia (n = 10) and cytopenias (n = 3) were prominent side‐effects, but the drug was generally well tolerated. Mutations in the P‐loop of the BCR‐ABL kinase domain were found in 2 of the patients who responded to the addition of sHHT.CONCLUSIONSThe addition of sHHT should be considered for patients on imatinib who fail to obtain low levels of minimal residual disease. Cancer 2005. © 2005 American Cancer Society.
There has been increasing experience in the utilization of intraoperative magnetic resonance imaging (iMRI) for intracranial surgery. Despite this trend, only a few U.S centers have examined the use of this technology for transsphenoidal resection of tumors of the sella. We present the largest series in North America examining the role of iMRI for pituitary adenoma resection. We retrospectively reviewed our institutional experience of 59-patients who underwent transsphenoidal procedures for sellar and suprasellar tumors with iMRI guidance. Of these, 52 patients had a histological diagnosis of pituitary adenoma. The technical results of this subgroup were examined. A 1.5-T iMRI was integrated with the BrainLAB (Feldkirchen, Germany) neuronavigation system. The majority (94%) of tumors in our series were macroadenomas. Seventeen percent of tumors were confined to the sella, 49% had suprasellar extensions without involvement of the cavernous sinus, 34% had frank cavernous sinus invasion. All patients underwent at least one iMRI, and 19% required one or more additional sets of intraoperative imaging. In 58% of patients, iMRI led to the surgeon attempting more resection. A gross total resection was obtained in 67% of the patients with planned total resections. There was one case of permanent postoperative diabetes insipidus and no other instances of new hormone replacement. In summary, iMRI was most useful for tumors of the sella with and without suprasellar extension where the information from the iMRI extended the complete resection rate from 40 to 72% and 55 to 88%, respectively. As one would expect, it did not substantially increase the rate of resection of tumors with cavernous sinus invasion. Overall, iMRI was particularly useful in guiding resection safely, aiding in clinical decision making, and allowing identification and preservation of the pituitary stalk and normal pituitary gland. Limitations of the iMRI include a need for additional personnel and training as well as additional operative time, which diminishes over time as personnel learn to optimize workflow efficiency. Additional costs are mitigated in part by using the iMRI as an immediate postoperative scan. Other data emerging from our experience suggest that preservation of normal gland and
PPX could not be safely combined with temozolomide due to grade 4 hematologic toxicity. However, the favorable progression-free and overall survival suggest that PPX may enhance radiation for glioblastoma. A randomized study of single agent PPX/radiation versus temozolomide/radiation for glioblastoma without MGMT methylation is underway.
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