Search

Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed., Methods and Materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward., Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41)., Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Laboratory and clinical studies support the concept that heparins, particularly the low molecular component, may serve as an inhibitor of angiogenesis, providing anti-neoplastic effects. Further, treatment with low molecular weight heparin (LMWH) may provide prophylaxis for thromboembolic events (TEE), in glioblastoma (GBM) patients. Dalteparin (5,000 U sub-Q daily) was given with and after conventional radiotherapy to newly diagnosed GBM patients. Forty-five patients were accrued between 5/02 and 9/04; 3 were ineligible. At time of progression, patients could continue dalteparin in addition to standard regimens. Pretreatment characteristics included: median age 61 (range 26-78); ECOG Performance status: 0 = 38%, 1 = 57%, 2 = 5%; gross total resection 45%. There were no grade 3/4 bleeding or thrombocytopenic events, and no TEE occurred while on dalteparin. Median time on dalteparin was 6.3 months, median time to progression was 3.9 months; median survival was 11.9 months. There was no significant improvement in survival when compared to the RTOG GBM database (with various radiation/drug doublets including BCNU) using recursive partitioning analysis. Historically the incidence of TEE in GBM patients is approximately 30%. As this study suggests dalteparin reduces the incidence of TEE, and does not have significant overlapping toxicities with most other drugs; its testing in a combined modality approach with other medications may be warranted in future trials.

A case of germ cell carcinoma (of presumed testicular origin) is described in which acute lymphocytic leukemia developed within nine months of the diagnosis. Possible relationships between the two neoplasms are discussed, as well as the need for continued observation of patients with germ cell tumors as they are living longer and may be at higher risk for developing a second cancer.