Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

The Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium Protocol 95-01 was designed to minimize therapy-related morbidity for children with newly diagnosed ALL without compromising efficacy. Patients participated in randomized comparisons of (1) doxorubicin given with or without dexrazoxane, a cardioprotectant (high-risk patients), (2) intensive intrathecal chemotherapy and cranial radiation (standard-risk patients), and (3) Erwinia and Escherichia coli asparaginase (all patients). Between 1996 and 2000, 491 patients (aged 0-18 years) were enrolled (272 standard risk and 219 high risk). With a median of 5.7 years of followup, the estimated 5-year event-free survival (EFS) for all patients was 82% ؎ 2%. Dexrazoxane did not have a significant impact on the 5-year EFS of high-risk patients (P ‫؍‬ .99), and there was no significant difference in outcome of standardrisk patients based on type of central nervous system (CNS) treatment (P ‫؍‬ .26).Compared with E coli asparaginase, Erwinia asparaginase was associated with a lower incidence of toxicity (10% versus 24%), but also an inferior 5-year EFS (78% ؎ 4% versus 89% ؎ 3%, P ‫؍‬ .01). We conclude that (1) dexrazoxane does not interfere with the antileukemic effect of doxorubicin, (2) intensive intrathecal chemotherapy is as effective as cranial radiation in preventing CNS relapse in standard-risk patients, and (3) onceweekly Erwinia is less toxic than E coli asparaginase, but also less efficacious.

T-ALL patients fared as well as B-progenitor patients on DFCI ALL Consortium protocols. Patients with T-ALL remain at increased risk for induction failure, early relapse, and isolated CNS relapse. Future studies should focus on the identification of and treatment for T-ALL patients at high risk for treatment failure.

Background-Asparaginase, an agent used in the treatment of acute lymphoblastic leukemia (ALL), is associated with the development of pancreatitis. The clinical course and long-term outcome of patients experiencing this complication has not been extensively detailed.

Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival.

High-dose bevacizumab added to IFL is a well-tolerated and highly active regimen in patients with previously untreated metastatic colorectal cancer.

Purpose-Among men with either extracapsular disease or positive surgical margins after radical prostatectomy, immediate adjuvant therapy decreases the risk of biochemical recurrence at the cost of increased toxicity. We sought to further stratify these men into a low-risk group in whom watchful waiting after surgery may be preferred and a high-risk cohort in whom adjuvant therapy may be preferred. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Materials and Methods-We NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptCox proportional hazards regression model, we generated tables to estimate the risk of recurrence at 1, 3 and 5 years after surgery.Results-After a median of 3 years of follow-up, 346 (39%) patients developed a biochemical recurrence. On multivariate analysis, the significant predictors of biochemical recurrence included age >60 years, PSA >10 ng/ml, Gleason score 4+3 and 8-10, 2 or more sites of positive surgical margins and prostate specimen weight ≤30 grams. The overall predictive accuracy of the model as determined by the Concordance Index C was 0.67, which compared to 0.60 for the post-operative "Kattan nomogram" for this patient population.Conclusions-We have developed a simple instrument, which once validated, may aid in the postoperative decision making process for men with intermediate risk of recurrence after prostatectomy.

Background:The epidermal growth factor receptor (EGFR) has been implicated in tumor growth and progression. Intron 1 of the EGFR gene contains a polymorphic simple sequence repeat (SSR) of 14 to 21 CA dinucleotides, the length of which correlates inversely with the level of EGFR transcription. The authors hypothesized that a shorter length of tumor SSR would be associated with poorer survival in patients with non-small cell lung cancer (NSCLC). Methods: Patients enrolled in Eastern Cooperative Oncology Group E3590 (a randomized, prospective trial of adjuvant therapy following resection of stages II and IIIa NSCLC) were randomized to radiation or radiation plus chemotherapy. Genomic DNA extracted from resected tumors was amplified for EGFR intron 1 by polymerase chain reaction and sequenced in a 3730XL DNA analyzer. Results: One hundred fifty-seven primary tumors were sequenced, 106 (68%) of which were heterozygous for intron 1. The most common genotypes were allele lengths of 17/19 dinucleotides (17.8%), 17/18 (11.4%), and 19/19 (11.4%). Allele status (homozygous versus heterozygous) did not correlate with race, gender, weight, performance status, histology, stage, or survival. Shorter allele length (Յ18 versus Ͼ18 CA dinucleotide repeats) was associated with squamous cell histology (p ϭ 0.03). Allele sum of greater than 35 was associated with improved overall survival (log-rank p ϭ 0.03, hazard ratio ϭ 0.66). Conclusion: This is the first study to characterize the EGFR intron 1 SSR polymorphism in NSCLC. Tumors were most commonly heterozygous for SSR length. Squamous histology was associated with a shorter SSR. Longer sequences are associated with improved survival.