© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 5, 357,
March 1, 2000
© 2000 Oxford University Press
IN THIS ISSUE |
The conviction that postoperative radiotherapy and chemotherapy represent the standard of care for patients with Dukes’ B (stage II) and Dukes’ C (stage III) carcinoma of the rectum evolved in the absence of proper clinical trials designed to determine whether the addition of radiotherapy results in improved disease-free survival and overall survival. Wolmark et al. (p. 388) addressed this issue by conducting a randomized clinical trial (National Surgical Adjuvant Breast and Bowel Project [NSABP] Protocol R-02). Eligible patients were randomly assigned to receive postoperative adjuvant chemotherapy either alone or with postoperative radiotherapy. The authors conclude that the postoperative radiotherapy adds no benefit to the patient’s disease-free survival and overall survival, regardless of the chemotherapy regimen used. They did show that radiotherapy reduced the cumulative incidence of locoregional relapse of the cancer from 13% to 8%. However, it did not affect the incidence of distant disease at 5 years after treatment.
In an editorial, Haller (p. 361) notes that results of the NSABP R-02 trial challenge the status quo established by the National Institutes of Health Consensus Development Conference a decade ago recommending that all patients with stage II or III rectal cancer should receive postoperative combined modality therapy. He suggests that these results may prompt the evolution of innovative clinical trials to establish optimal therapies for patients with curatively resected rectal cancer.
"These findings from NSABP Protocol R-02 have potential relevance to the commonly accepted standard of care for carcinoma of the rectum."
—Wolmark et al.
HPV DNA Testing of Cervical Lesions
Human papillomavirus (HPV) infections appear to be central to the development of cervical cancer. As such, it is possible that testing for HPV DNA may be a useful tool in predicting cervical cancer risk. A nationwide team of researchers (p. 397) analyzed baseline data from a large, multicenter randomized trial to assess the utility of HPV DNA testing among women with low-grade squamous intraepithelial cervical lesions (LSILs). The investigators found that HPV DNA was detectable in 532 (82.9%) of 642 women whose Pap smears showed evidence of LSILs. Because so many women with LSILs are positive for HPV DNA, the authors conclude that HPV DNA testing has limited potential to provide useful information to assist in the clinical management of these patients.
In an accompanying editorial, Follen and Richards-Kortum (p. 363) discuss the historical context of HPV DNA testing and other cervical cancer screening methods. They also speculate on the implications of and questions raised by the current findings and on directions for future research.
Delivery Vehicles in Gene Therapy
To enhance the delivery of exogenous genes via viral vectors in gene therapy protocols, Siemens et al. (p. 403) evaluated various matrices as solid-state vehicles. They observed that a gelatin sponge matrix proved to be the most effective solid-state vehicle for delivering canary pox virus (ALVAC) vectors to target cells in culture. In addition, this matrix substantially enhanced expression of ALVAC-delivered reporter genes in tumor models when compared with fluid-phase delivery of virus. Substantial growth inhibition of established tumors was also observed when a combination of three recombinant ALVAC viruses that encoded interleukin 2, interleukin 12, and tumor necrosis factor-
was delivered. The authors conclude that efficient delivery of reporter genes using the method they describe may prove useful in solid tumor gene therapy protocols.
"Improving the delivery of viral vectors is paramount in any clinical gene therapy trial, and this is especially true for prostate cancer."
—Siemens et al.
HER2 Gene Polymorphisms and Risk of Breast Cancer
Alterations in the HER2 proto-oncogene may play a role in the development and prognosis of breast cancer. Xie et al. (p. 412) evaluated the presence of an isoleucine/valine polymorphism at codon 655 in this gene in 339 women with breast cancer and 361 healthy women in Shanghai, China. They report that, compared with women who carried two alleles encoding isoleucine at codon 655, women who carried one allele encoding valine (Val allele) had an increased risk of breast cancer, and women who carried two Val alleles had an even more pronounced elevation in risk. The association was also more pronounced among younger women (
45 years) than older women. The authors suggest that polymorphisms of the HER2 gene may be important susceptibility biomarkers for breast cancer risk, particularly among younger women.
Chemoprevention in a Mouse Mammary In Vitro Model
Recent in vivo and in vitro studies have shown that thiazolidinediones (such as troglitazone) and retinoids inhibit the growth of breast cancer cells. Mehta et al. (p. 418) evaluated the ability of troglitazone, with or without retinoids, to prevent the formation of preneoplastic lesions induced by 7,12-dimethylbenz[a]anthracene in a mouse mammary gland organ culture model.
They report that troglitazone and retinoic acid independently markedly inhibited the development of lesions. The combination of the two also inhibited the formation of mammary lesions but did not enhance either agent’s effect. Troglitazone in combination with LG10068, a selective retinoid X receptor ligand, almost completely inhibited lesion development; however, LG10068 was relatively inactive by itself. The authors suggest that a regimen that combines a peroxisome proliferator-activated receptor 
ligand (such as troglitazone) with a retinoid X receptor-selective retinoid (such as LG10068) may be a useful chemoprevention approach in humans.
"Individuals at high risk for developing breast cancer . . . may receive the benefit from a chemoprevention regimen containing [these novel compounds]."
—Mehta et al.
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