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Is Intermittent Imatinib Therapy for Chronic Myelogenous Leukemia an Option?
Taken chronically, imatinib has proved to be an extremely effective agent against chronic myelogenous leukemia (CML); however, this regimen is relatively expensive and it is not known whether intermittent treatment may provide similar outcomes in appropriate patients or whether withdrawal of therapy will promptly result in relapse.
A small study from St. Mary’s Hospital, Seoul, Korea, may provide some direction. Over six years at this facility, 555 patients had been treated with imatinib for Philadelphia chromosome–positive CML; 26 patients (median age, 35 yr; 54% men) had discontinued therapy for various reasons after achieving a complete cytogenetic (11 patients) or molecular (15 patients) response. If the patients suffered a relapse, imatinib therapy was reinitiated.
With a follow-up ranging to 48 months (mean, 7 mo), four patients suffered hematologic relapse, seven experienced cytogenetic relapse, and 10 had molecular relapses. Two patients did not suffer any relapse. One patient died. After readministration of imatinib treatment, all 23 remaining patients have maintained their best rated response compared with before discontinuing therapy.
Based on the results of this study, the researchers found that intermittent therapy is possible for appropriate patients, but that it is difficult to know which patients are best suited to discontinuation. They believe that a larger study with a longer follow-up will be necessary to answer this question more completely.
Goh H-G, Kim S-H, Lee J, et al: Outcomes of patients with chronic myeloid leukemia who received an intermittent imatinib therapy. Presented at the 49th annual meeting of the American Society of Hematology, Atlanta, December 9, 2007.Genetic Marker Predicts Treatment Resistance and Poor Outcomes in Esophageal Cancer
Patients with localized esophageal cancer can often benefit from chemotherapy and radiation treatment, but the prognosis varies considerably, for example, depending on stage of cancer at diagnosis. Another possible determinant of prognosis may be the ability of the tumor to express certain genes. This was tested by a team of oncologists, radiologists, surgeons, and pathologists at the Asan Medical Center, Seoul, South Korea.
Some esophageal tumors express excision repair cross complementation group 1 (ERCC1), others express increased thymidylate synthase (TS) production, and yet others demonstrate expression of both genes. The researchers biopsied tumors from 129 patients and tested these samples for over-expression of these genetic markers. These patients with esophageal cancer were treated preoperatively with 5-fluorouracil/ cisplatin or capecitabine/cisplatin plus radiation from March 1993 to June 2005.
Thirty-five percent of the biopsied samples (from 108 patients evaluable) tested positive for TS and 40% tested positive for ERCC1. The researchers found that patients who tested negative for either marker were more likely to achieve “pathologic major response.” Although negative tests for both genetic markers resulted in positive correlations for response, the test for ERCC1 was deemed the only independent variable that predicted the pathologic response (P
< .001). However, the prediction of pathologic response did not portend a statistically signifi- cant relationship with overall survival (P
= .10) and progression-free survival (P
The investigators conclude that although this was not a prospective study, it does show that the use of a genetic marker may help predict chemoradiation response or resistance in patients with esophageal cancer. They recommended prospective clinical trials to confirm this theory.
Kim MK, Cho KJ, Kwan GY, et al: ERCC1 predicting chemoradiation resistance and poor outcome in oesphageal cancer
. Eur J Cancer 2008;44:54-60.
Pelvic Radiation in Addition to Prostate Radiotherapy for Localized Prostate Cancer
Can patients with localized prostate adenocarcinoma who receive prostate radiotherapy also benefit from pelvic radiation? The literature is not clear on this question, and radiologists from Lyon, France, decided to test whether the broader radiation approach influences outcomes.
Over six years, the researchers randomly assigned patients with localized prostate cancer to receive prostate radiotherapy with or without pelvic radiotherapy. Inclusion criteria included tumors that were characterized as T1b-T3, N pNx, M0. Only patients taking short-term chemotherapy who deemed to be at high risk were included in the trial; otherwise, the use of chemotherapy excluded one from the study.
The dose of pelvic radiation was 46 Gy, and the dose of prostate radiation was 66 or 70 Gy.
Over a median 42-month follow-up, the fiveyear progression-free survival and overall survival were similar in both groups of patients. Nor did the researchers find any significant differences in gut toxicity. Therefore, they concluded, pelvic radiation did not contribute to improved outcomes in patients with local prostate cancer who were undergoing prostate radiotherapy.